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Sample records for live attenuated mumps

  1. Evaluation of live attenuated S79 mumps vaccine effectiveness in mumps outbreaks: a matched case-control study

    Institute of Scientific and Technical Information of China (English)

    FU Chuan-xi; NIE Jun; LIANG Jian-hua; WANG Ming

    2009-01-01

    Background Mumps virus infection is a potentially serious viral infection of childhood and early adulthood. In China, live attenuated S79 mumps vaccine has been licensed for pediatric use since 1990. The objective of this study was to determine the effectiveness of live attenuated S79 mumps vaccine against clinical mumps in outbreaks.Methods Cases were selected from mumps outbreaks in schools in Guangzhou between 2004 and 2005. Each case was matched by gender, age and classroom. Vaccination information was obtained from Children's EPI Administrative Computerized System. Vaccine effectiveness (VE) was calculated for 1 or 2 doses of S79 vaccine with 95% confidence intervals (CI).Results One hundred and ninety-four cases and 194 controls were enrolled into the study. VE of the S79 mumps vaccine for 1 dose versus 0 confer protection 80.4% (95% CI, 60.0%-90.4%) and Ves against mumps in outbreaks for 1 dose of mumps vaccine are similar among those children aged 4-9 years and aged over 10 years old.Conclusion The live attenuated S79 mumps vaccine can be effective in preventing clinical mumps outbreaks.

  2. Effects of the live attenuated measles-mumps-rubella booster vaccination on disease activity in patients with juvenile idiopathic arthritis : a randomized trial

    NARCIS (Netherlands)

    Heijstek, Marloes W; Kamphuis, Sylvia; Armbrust, Wineke; Swart, Joost; Gorter, Simone; de Vries, Lara D; Smits, Gaby P; van Gageldonk, Pieter G; Berbers, Guy A M; Wulffraat, Nico M

    2013-01-01

    IMPORTANCE: The immunogenicity and the effects of live attenuated measles-mumps-rubella (MMR) vaccination on disease activity in patients with juvenile idiopathic arthritis (JIA) are matters of concern, especially in patients treated with immunocompromising therapies. OBJECTIVES: To assess whether M

  3. Live attenuated measles and mumps viral strain-containing vaccines and hearing loss: Vaccine Adverse Event Reporting System (VAERS), United States, 1990--2003.

    Science.gov (United States)

    Asatryan, Armenak; Pool, Vitali; Chen, Robert T; Kohl, Katrin S; Davis, Robert L; Iskander, John K

    2008-02-26

    Hearing loss (HL) is a known complication of wild measles and mumps viral infections. As vaccines against measles and mumps contain live attenuated viral strains, it is biologically plausible that in some individuals HL could develop as a complication of vaccination against measles and/or mumps. Our objectives for this study were: to find and describe all cases of HL reported in the scientific literature and to the US Vaccine Adverse Events Reporting System (VAERS) for the period 1990--2003; and to determine reporting rate of HL after live attenuated measles and/or mumps viral strain-containing vaccines (MMCV) administration. We searched published reports for cases of HL identified after vaccination with MMCV. We also searched for reports of HL after MMCV administration submitted to VAERS from 1990 through 2003 and determined the dose-adjusted reporting rate of HL. Our main outcome measure was reported cases of HL after immunization with MMCV which were classified as idiopathic. We found 11 published case reports of HL following MMCV. The review of the VAERS reports identified 44 cases of likely idiopathic sensorineural HL after MMCV administration. The onset of HL in the majority of VAERS and published cases was consistent with the incubation periods of wild measles and mumps viruses. Based on the annual usage of measles-mumps-rubella (MMR) vaccine, we estimated the reporting rate of HL to be 1 case per 6-8 million doses. Thus, HL following MMCV has been reported in the literature and to the VAERS. Further studies are needed to better understand if there is a causal relationship between MMCV and HL.

  4. The immunizing effect and reactogenicity of two live attenuated mumps virus vaccines in Swedish schoolchildren.

    Science.gov (United States)

    Christenson, B; Heller, L; Böttiger, M

    1983-10-01

    An evaluation of the seroconversion and booster effects after vaccination with two different mumps vaccines, the Urabe Am 9 strain and the Jeryl Lynn strain, was carried out in schoolchildren. Four hundred and fifty-four schoolchildren aged 11 to 12 years with no previous history of mumps or mumps vaccination were enrolled for the study. The antibody responses were measured by serum neutralization (SN) and haemolysis-in-gel (HIG) tests. Of the 454 subjects, 130 were found to be initially seronegative. Two lots of different strengths of each vaccine were used to evaluate the relationships. The Urabe Am 9 vaccine lots had infectivity titres of 100 000 and 19 000 TCID50 per dose and the Jeryl Lynn vaccine titres of 59 000 and 28 000 TCID50 per dose. Only slight differences in seroconversion rates were seen between the lots. The overall seroconversion rate, measured by SN, was 94% for the Urabe Am 9 vaccine and 91% for the Jeryl Lynn vaccine, whereas the geometric mean titre for virus-neutralizing antibody in seroconverting children was 7.4 with the Urabe Am 9 vaccine and 10.7 with the Jeryl Lynn vaccine. In children who were seropositive prior to vaccination, a marked rise in antibody titre was found 8 weeks after vaccine injection indicating a booster effect. The miscellaneous post-vaccination side-effects were mild and inconsequential.

  5. 不同滴度麻疹腮腺炎风疹联合减毒活疫苗安全性观察%SECURITY CHECK ON DIFFERENT TITERS OF MEASLES MUMPS RUBELLA COMBINED LIVE ATTENUATED VACCINES

    Institute of Scientific and Technical Information of China (English)

    王标; 陶红; 叶循; 王树巧; 储艳; 荀以标

    2012-01-01

    [Objective] To discuss the security of different liters of measles, mumps, rubella combined live attenuated vaccine(MMR) in Biological Products of shanghai institute. To provide the scientific basis for scientific use. [Methods] Selected three hundred children aged 8 to IS months to vaccinate high-liter of Shanghai MMR, low-tiler of Shanghai MMR. While selected one hundred and a half children aged 8 to 15 months for MMR vaccine in the Beijing Biological Institute as controls for safely observation. (Results j After 8 to IS months children were vaccinated wilh high-tiler of Shanghai MMR vaccine, low- liter of Shanghai MMR vaccine and Beijing MMR, the incidence of adverse reactions was 17.33%. 21.33% and 17.33%, respectively. And incidence of fever was 15.33%,15.67%,14.67% respectively. Among them, all reactions to Beijing MMR vaccination were mtld fever, 3 cases of strong reaction of fever with high-liter of Shanghai MMR vaccination. One case of fever strong reaction occurred after low -tiler of Shanghai MMR vaccination. The abnormal responses of high and low liters of Shanghai MMR vaccination compared with the control vaccine were not statistically significant. [Conclusion] The different tilers of Shanghai MMR vaccine have the same immunization safely with vaccine currently used.%[目的]研究上海生物制品研究所的不同滴度麻疹,腮腺炎、风疹三联联合减毒活疫苗(MMR)的安全性,为疫苗的使用提供科学依据.[方法]分别选择8~15月龄儿童各300名接种高滴度沪MMR、低滴度沪MMR,同时选择8~15月龄儿童150名接种北京生物所MMR疫苗作对照,进行安全性观察.[结果]8~15儿童接种高滴度沪MMR疫苗、低滴度沪MMR疫苗、京MMR后,不良反应的发生率分别为17.33%、21.33%、17.33%.发热反应发生率分别依次为:15.33%,15.67%,14.67%.其中京MMR全部为中轻度发热反应,高滴度沪MMR接种后发生3例发热强反应,低滴度MMR接种后发生1例发热强反

  6. LIVE ATTENUATED VACCINES FOR THE IMMUNOPROPHYLAXIS

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    O. A. Shamsutdinova

    2017-01-01

    Full Text Available The review focuses on the history of the production of live antiviral vaccines and their use for the prevention of infectious diseases. It was noted that before the beginning of the 20th century, only three live vaccines were developed and put into practice — against smallpox, rabies, plague. The discovery of D. Enders, T.H. Weller and F.Ch. Robins of the ability of the polio virus, and then of a number of other viruses, to reproduce in vitro in cell cultures of various types, greatly expanded the studies on the production of attenuated strains of viruses for live vaccines. The historical stages of obtaining and introducing live vaccines for the prevention of smallpox, poliomyelitis, measles, rubella, and mumps are highlighted. Arguments in favor of the use of associated vaccine preparations for the prevention of viral infections are presented. Various variants of the strategy and tactics of using live vaccines, which are used for specific prevention of viral infections in different countries, are described. The review provides information on technological methods for obtaining antiviral vaccines. The publications testifying to the development of specific reactions in immunized vaccine strains of measles, mumps, poliomyelitis and rubella viruses, such as aseptic meningitis (vaccine strains of mumps virus, acute arthritis (vaccine rubella virus strains, temperature reactions, rash (vaccine strains of the virus Measles, vaccine-associated paralytic poliomyelitis (VAPP vaccine vaccine poliovirus. It is particularly noted that the long experience of vaccine prevention both in Russia and abroad convincingly shows that the risk of developing post-vaccination complications is incommensurably lower than the risk of causing harm to health from the corresponding infections. It is concluded that despite introduction of new third and fourth generation vaccines into practice, live attenuated vaccines do not lose their significance and are used in vaccine

  7. Safety Surveillance of Measles Attenuated Live Vaccine and Measles-Mumps-Rubella Combined Attenuated Live Vaccine after Supplementary Immunization Activities in Shanghai, 2010%上海市2010年强化免疫活动中麻疹减毒活疫苗和麻疹-流行性腮腺炎-风疹联合减毒活疫苗的安全性观察

    Institute of Scientific and Technical Information of China (English)

    白庆瑞; 杨建萍; 陆菁; 黄卓英; 李智; 王于超; 秦晓东; 陶黎纳; 胡家瑜

    2011-01-01

    目的 了解上海市2010年强化免疫活动(Supplementary Immunization Activites,SIA)中,麻疹减毒活疫苗(Measles Attenuated Live Vaccine,MV)和麻疹-流行性腮腺炎-风疹联合减毒活疫苗(Measles,Mumps and Rubella Combined Attenuated Live Vaccine,MMR)的安全性.方法 通过上海市疑似预防接种异常反应(Adverse Events Following Immunization,AEFI)监测系统收集MV和MMR联合疫苗的AEFI信息,分析其AEFI发生情况.结果 2010年9月11日~10月20日,上海市SIA共接种81.40万剂MV和97.75万剂MMR联合疫苗.MV的一般反应和异常反应报告发生率分别为109.33/10万剂和13.51/10万剂,MMR联合疫苗一般反应和异常反应报告发生率分别为20.87/10万剂和3.99/10万剂.MV的AEFI病例中,年龄越小所占构成比越大.两种疫苗的AEFI均以发热和局部红肿等一般反应为主,报告的异常反应中以过敏性皮疹为主.结论 使用MV或MMR联合疫苗进行SIA安全性良好.%Objective To investigate the safety of the measles attenuated live vaccine ( MV ) and measles-mumps-rubella combined attenuated live vaccine (MMR) after the supplementary immunization activities (SIA)in Shanghai in 2010. Methods The surveillance data was analyzed which were collected through Shanghai adverse events following immunization (AEFI) surveillance system. Results From September 11, 2010 to October 20, 2010, 0.814 million children were vaccinated by MV and 0.9775 million were vaccinated by MMR. The reported rate of common adverse reaction of MV was 109.33/100,000 and 13.51/100,000, respectively. The reported rate of rare adverse reaction of MMR was 20.87/100,000 and 3.99/100,000, respectively. The younger group is the greater proportion of reported MV AEFI cases. The reported AEFI was mainly common adverse reaction, such as fever and local swelling. The rare adverse reaction was mostly allergic rash. Conclusions The vaccination of MV and MMR in SIA was safe and the most reaction was common adverse

  8. 儿童接种麻腮风联合减毒活疫苗的安全性及免疫学效果观察%Safety and Immunological Effects of Measles-mumps-rubella Attenuated Live Vaccine in Children

    Institute of Scientific and Technical Information of China (English)

    吴媛; 黎丽

    2016-01-01

    OBJECTIVE:To observe the safety and immunological effects of Measles-mumps-rubella(MMR)attenuated live at-tenuated vaccine in children. METHODS:300 children aged 8-12 months receiving inoculation were selected from Changsha Hospi-tal for Maternal and Child Health Care during Jan. 2015-Apr. 2016 to observe safety and immunological effects. Those children were divided into MMR group,measles vaccine group,mumps vaccine group and rubella vaccine group according to vaccine type, with 75 cases in each group. The occurrence of ADR in 72 h were compared among 4 groups after inoculation;venous blood of chil-dren was collected before vaccination and 5 months after vaccination,and the antibody positive test was carried out by micro coagu-lation inhibition (HI) test;HI antibody titer was recorded after immunization,and positive rate and genometric meantiter(GMT) were calculated. RESULTS:The incidence of ADR in 4 groups were 9.33%,8.00%,8.00% and 10.67%,respectively. No local ADR was found in 4 groups;among systemic ADR,the incidence of fever was higher than that of other clinical manifestations,be-ing 4.00%,4.00%,4.00% and 5.33%;there was no statistical significance in the incidence of ADR among 4 groups(P>0.05). Measles,mumps and rubella antibody positive rates of MMR group were 100%,92.00% and 100%,respectively;antibody posi-tive rates of measles vaccine group,mumps vaccine group and rubella vaccine group were 100%,85.33% and 100%,respective-ly;there was no statistical significance in same antibody positive rate among 4 groups(P>0.05). GMT of measles in MMR group and measles vaccine group were 1∶41 and 1∶27,that of mumps in MMR group and mumps vaccine group were 1∶6.3 and 1∶6.2, there was no statistical significance (P>0.05);GMT of rubella in MMR group and rubella vaccine group were 1∶320 and 1∶849, with statistical significance (P<0.05). CONCLUSIONS:Compared to traditional single vaccine,MMR dose not increase the inci-dence of ADR and not influence positive rate

  9. 麻腮风联合减毒活疫苗中新霉素残留量微生物学检测方法的建立%Development of a microbiological method for detection of residual neomycin content in live attenuated measles, mumps and rubella combined vaccine

    Institute of Scientific and Technical Information of China (English)

    常艳; 杨美琴; 李景云; 胡昌勤

    2013-01-01

    目的 建立麻腮风联合减毒活疫苗(Measles,mumps and rubella vaccine,MMR)中新霉素残留量的微生物学检测方法,并进行验证.方法 采用管碟法测定新霉素含量,并以新霉素浓度的对数和抑菌圈半径的平方值绘制标准直线.对建立的方法进行同质性、最低检出限、加样回收率及精密度验证.结果 建立的方法在新霉素浓度为0.24~4.18U/ml的范围内线性关系良好,R2=0.997 8;新霉素标准品与供试品的剂量反应直线的回归方程的斜率差异无统计学意义(P>0.05),即标准品与供试品间可满足同质性的要求;该方法的最低检出限为0.05 U/ml;该方法检测新霉素浓度约为0.5和1.0 U/ml的混合溶液,回收率分别为99.22%和99.86%;日内RSD为1.09%,日间RSD为1.42%.结论 建立了一种适用于定量测定MMR中新霉素残留量的微生物学检测方法,该方法操作简便,结果可靠,可用于MMR的常规质量控制.%Objective To develop and verify a microbiological method for detection of residual neomycin content in live attenuated measles, mumps and rubella combined vaccine (MMR). Methods The neomycin content was determined by cylinder plate method, based on which a standard curve was plotted with the log of neomycin concentration against the square of radius of bacteriostatic ring. The developed method was verified for homogeneity, limit of detection (LOD), recovery rate and precision. Results The developed method showed good linearity within a neomycin concentration range of 0. 24 ~ 4. 18 U/ ml (R2 - 0. 997 8). No significant difference was observed between the slopes of dose-response curves of standard neomycin and test samples (P> 0. 05), which met the requirements for homogeneity. The LOD of the developed method was 0. 05 U / ml. By the developed method, the recovery rates of mixed samples at neomycin concentrations of 0. 5 and 1. 0 U/ml were 99. 22% and 99. 86%, while the intra- and inter-RSDs were 1. 09

  10. Quality comparability study on manufacturing site change of live attenuated measles, mumps and rubella combined vaccine%麻疹-腮腺炎-风疹联合减毒活疫苗生产场地变更的质量可比性研究

    Institute of Scientific and Technical Information of China (English)

    沈坚; 杨文震; 齐嘉; 马相虎; 陈哲文

    2015-01-01

    目的 比较生产场地变更前后生产的麻疹-腮腺炎-风疹联合减毒活疫苗(麻腮风疫苗)的关键质量指标及其变化趋势.方法 新老车间同步各生产3批麻腮风疫苗,比较新老车间生产的疫苗的关键指标及其变化趋势,同时对新老车间生产的疫苗进行稳定性和安全性比较研究.结果 新老车间生产的疫苗成品的关键质量指标均符合相关规定的要求,其中新车间生产的疫苗的水分为1.6%~1.8%,其麻疹、腮腺炎和风疹病毒滴度分别为4.1~4.3、4.8~5.0和3.9~4.1 lgCCID50/ml,与老车间生产的疫苗(水分为1.6%~2.1%,麻疹、腮腺炎和风疹病毒滴度分别4.0~4.3、4.8~5.0和4.1~4.2 lgCCID50/ml)相似.新老车间生产的疫苗成品的稳定性和安全性实验结果均符合相关规定的要求,且新老车间生产的疫苗的稳定性实验结果相似,新老车间生产的疫苗的抗生素残留量(t=3.46,P>0.05)和牛血清白蛋白残留量(t=2.00,P>0.05)间的差异无统计学意义.结论 麻腮风疫苗生产场地变更未对其制品质量产生影响.%Objective To compare the key quality indicators (KQIs) of live attenuated measles,mumps and rubella combined vaccine (MMR) and their changing trends between before and after manufacturing site change.Methods Three batches of MMR per site were prepared in new and old workshops simultaneously.KQIs of MMR and their changing trends were compared between new and old workshops.The stability and safety of MMR prepared in new and old workshops were compared.Results KQIs of MMR prepared in new and old workshops were both in compliance with related requirements.The residual moisture contents of 3 batches of MMR prepared in new workshop were 1.6%-1.8%,and viral titers of measles,mumps and rubella vaccine were 4.1-4.3,4.8-5.0 and 3.9-4.1 lgCCID50/ml,respectively,similar to those in old workshop (residual moisture contents were 1.6%-2.1%,and viral titers were 4

  11. Live attenuated intranasal influenza vaccine.

    Science.gov (United States)

    Esposito, Susanna; Montinaro, Valentina; Groppali, Elena; Tenconi, Rossana; Semino, Margherita; Principi, Nicola

    2012-01-01

    Annual vaccination is the most effective means of preventing and controlling influenza epidemics, and the traditional trivalent inactivated vaccine (TIV) is by far the most widely used. Unfortunately, it has a number of limitations, the most important of which is its poor immunogenicity in younger children and the elderly, the populations at greatest risk of severe influenza. Live attenuated influenza vaccine (LAIV) has characteristics that can overcome some of these limitations. It does not have to be injected because it is administered intranasally. It is very effective in children and adolescents, among whom it prevents significantly more cases of influenza than the traditional TIV. However, its efficacy in adults has not been adequately documented, which is why it has not been licensed for use by adults by the European health authorities. LAIV is safe and well tolerated by children aged > 2 y and adults, but some concerns arisen regarding its safety in younger children and subjects with previous asthma or with recurrent wheezing. Further studies are needed to solve these problems and to evaluate the possible role of LAIV in the annual vaccination of the general population.

  12. Easy and Rapid Detection of Mumps Virus by Live Fluorescent Visualization of Virus-Infected Cells.

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    Tadanobu Takahashi

    Full Text Available Mumps viruses show diverse cytopathic effects (CPEs of infected cells and viral plaque formation (no CPE or no plaque formation in some cases depending on the viral strain, highlighting the difficulty in mumps laboratory studies. In our previous study, a new sialidase substrate, 2-(benzothiazol-2-yl-4-bromophenyl 5-acetamido-3,5-dideoxy-α-D-glycero-D-galacto-2-nonulopyranosidonic acid (BTP3-Neu5Ac, was developed for visualization of sialidase activity. BTP3-Neu5Ac can easily and rapidly perform histochemical fluorescent visualization of influenza viruses and virus-infected cells without an antiviral antibody and cell fixation. In the present study, the potential utility of BTP3-Neu5Ac for rapid detection of mumps virus was demonstrated. BTP3-Neu5Ac could visualize dot-blotted mumps virus, virus-infected cells, and plaques (plaques should be called focuses due to staining of infected cells in this study, even if a CPE was not observed. Furthermore, virus cultivation was possible by direct pick-up from a fluorescent focus. In conventional methods, visible appearance of the CPE and focuses often requires more than 6 days after infection, but the new method with BTP3-Neu5Ac clearly visualized infected cells after 2 days and focuses after 4 days. The BTP3-Neu5Ac assay is a precise, easy, and rapid assay for confirmation and titration of mumps virus.

  13. Live attenuated vaccines for invasive Salmonella infections.

    Science.gov (United States)

    Tennant, Sharon M; Levine, Myron M

    2015-06-19

    Salmonella enterica serovar Typhi produces significant morbidity and mortality worldwide despite the fact that there are licensed Salmonella Typhi vaccines available. This is primarily due to the fact that these vaccines are not used in the countries that most need them. There is growing recognition that an effective invasive Salmonella vaccine formulation must also prevent infection due to other Salmonella serovars. We anticipate that a multivalent vaccine that targets the following serovars will be needed to control invasive Salmonella infections worldwide: Salmonella Typhi, Salmonella Paratyphi A, Salmonella Paratyphi B (currently uncommon but may become dominant again), Salmonella Typhimurium, Salmonella Enteritidis and Salmonella Choleraesuis (as well as other Group C Salmonella). Live attenuated vaccines are an attractive vaccine formulation for use in developing as well as developed countries. Here, we describe the methods of attenuation that have been used to date to create live attenuated Salmonella vaccines and provide an update on the progress that has been made on these vaccines.

  14. Facts about Mumps for Adults

    Science.gov (United States)

    ... Recommendation: MMR About Mumps Measles, Mumps, Rubella (MMR) Facts about Mumps for Adults What is Mumps? Mumps ... are pregnant or severely immunosuppressed. Disease and vaccine facts FACT: Mumps can be prevented with a safe ...

  15. Live attenuated influenza vaccine--a review.

    Science.gov (United States)

    Gasparini, R; Amicizia, D; Lai, P L; Panatto, D

    2011-09-01

    Owing to the variability of influenza viruses, vaccine composition needs to be up-dated annually. As many variables can influence their efficacy, vaccines are still considered "sub-optimal". Many studies have been carried out in recent years to improve vaccines. In particular, researchers and vaccine-producing corporations have focused on developing a live vaccine. Among the candidate vaccines, the strain developed by Maassab has recently been licensed in the USA and Europe, after extensive investigation. This vaccine is safe and well tolerated, and has shown very good genetic stability. Although vaccine recipients are able to spread the virus, transmission to close contacts is practically non-existent. Studies on cold-adapted attenuated influenza vaccines have demonstrated that such vaccines are effective, and sometimes more effective than inactivated influenza vaccines. Cold-adapted attenuated influenza vaccines therefore appear to be an important weapon against influenza. However, a more widespread use of these vaccines is to be recommended, especially in children, as the more acceptable way of administration can favour parental compliance.

  16. No evidence of murine leukemia virus-related viruses in live attenuated human vaccines.

    Directory of Open Access Journals (Sweden)

    William M Switzer

    Full Text Available BACKGROUND: The association of xenotropic murine leukemia virus (MLV-related virus (XMRV in prostate cancer and chronic fatigue syndrome reported in previous studies remains controversial as these results have been questioned by recent data. Nonetheless, concerns have been raised regarding contamination of human vaccines as a possible source of introduction of XMRV and MLV into human populations. To address this possibility, we tested eight live attenuated human vaccines using generic PCR for XMRV and MLV sequences. Viral metagenomics using deep sequencing was also done to identify the possibility of other adventitious agents. RESULTS: All eight live attenuated vaccines, including Japanese encephalitis virus (JEV (SA-14-14-2, varicella (Varivax, measles, mumps, and rubella (MMR-II, measles (Attenuvax, rubella (Meruvax-II, rotavirus (Rotateq and Rotarix, and yellow fever virus were negative for XMRV and highly related MLV sequences. However, residual hamster DNA, but not RNA, containing novel endogenous gammaretrovirus sequences was detected in the JEV vaccine using PCR. Metagenomics analysis did not detect any adventitious viral sequences of public health concern. Intracisternal A particle sequences closest to those present in Syrian hamsters and not mice were also detected in the JEV SA-14-14-2 vaccine. Combined, these results are consistent with the production of the JEV vaccine in Syrian hamster cells. CONCLUSIONS: We found no evidence of XMRV and MLV in eight live attenuated human vaccines further supporting the safety of these vaccines. Our findings suggest that vaccines are an unlikely source of XMRV and MLV exposure in humans and are consistent with the mounting evidence on the absence of these viruses in humans.

  17. Recurrent 6th nerve palsy in a child following different live attenuated vaccines: case report

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    Cheng Daryl R

    2012-04-01

    Full Text Available Abstract Background Recurrent benign 6th nerve palsy in the paediatric age group is uncommon, but has been described following viral and bacterial infections. It has also been temporally associated with immunization, but has not been previously described following two different live attenuated vaccines. Case presentation A case is presented of a 12 month old Caucasian boy with recurrent benign 6th nerve palsy following measles-mumps-rubella and varicella vaccines, given on separate occasions with complete recovery following each episode. No alternate underlying etiology was identified despite extensive investigations and review. Conclusions The majority of benign 6th nerve palsies do not have a sinister cause and have an excellent prognosis, with recovery expected in most cases. The exact pathophysiology is unknown, although hypotheses including autoimmune mechanisms and direct viral invasion could explain the pathophysiology behind immunization related nerve palsies. It is important to rule out other aetiologies with thorough history, physical examination and investigations. There is limited information in the literature regarding the safety of a repeat dose of a live vaccine in this setting. Future immunizations should be considered on a case-by-case basis.

  18. Molecular basis of live-attenuated influenza virus.

    Directory of Open Access Journals (Sweden)

    Wen He

    Full Text Available Human influenza is a seasonal disease associated with significant morbidity and mortality. The most effective means for controlling infection and thereby reducing morbidity and mortality is vaccination with a three inactivated influenza virus strains mixture, or by intranasal administration of a group of three different live attenuated influenza vaccine strains. Comparing to the inactivated vaccine, the attenuated live viruses allow better elicitation of a long-lasting and broader immune (humoral and cellular response that represents a naturally occurring transient infection. The cold-adapted (ca influenza A/AA/6/60 (H2N2 (AA ca virus is the backbone for the live attenuated trivalent seasonal influenza vaccine licensed in the United States. Similarly, the influenza A components of live-attenuated vaccines used in Russia have been prepared as reassortants of the cold-adapted (ca H2N2 viruses, A/Leningrad/134/17/57-ca (Len/17 and A/Leningrad/134/47/57-ca (Len/47 along with virulent epidemic strains. However, the mechanism of temperature-sensitive attenuation is largely elusive. To understand how modification at genetic level of influenza virus would result in attenuation of human influenza virus A/PR/8/34 (H1N1,A/PR8, we investigated the involvement of key mutations in the PB1 and/or PB2 genes in attenuation of influenza virus in vitro and in vivo. We have demonstrated that a few of residues in PB1 and PB2 are critical for the phenotypes of live attenuated, temperature sensitive influenza viruses by minigenome assay and real-time PCR. The information of these mutation loci could be used for elucidation of mechanism of temperature-sensitive attenuation and as a new strategy for influenza vaccine development.

  19. A novel live-attenuated vaccine candidate for mayaro Fever.

    Science.gov (United States)

    Weise, William J; Hermance, Meghan E; Forrester, Naomi; Adams, A Paige; Langsjoen, Rose; Gorchakov, Rodion; Wang, Eryu; Alcorn, Maria D H; Tsetsarkin, Konstantin; Weaver, Scott C

    2014-08-01

    Mayaro virus (MAYV) is an emerging, mosquito-borne alphavirus that causes a dengue-like illness in many regions of South America, and which has the potential to urbanize. Because no specific treatment or vaccine is available for MAYV infection, we capitalized on an IRES-based approach to develop a live-attenuated MAYV vaccine candidate. Testing in infant, immunocompetent as well as interferon receptor-deficient mice demonstrated a high degree of attenuation, strong induction of neutralizing antibodies, and efficacy against lethal challenge. This vaccine strain was also unable to infect mosquito cells, a major safety feature for a live vaccine derived from a mosquito-borne virus. Further preclinical development of this vaccine candidate is warranted to protect against this important emerging disease.

  20. A novel live-attenuated vaccine candidate for mayaro Fever.

    Directory of Open Access Journals (Sweden)

    William J Weise

    2014-08-01

    Full Text Available Mayaro virus (MAYV is an emerging, mosquito-borne alphavirus that causes a dengue-like illness in many regions of South America, and which has the potential to urbanize. Because no specific treatment or vaccine is available for MAYV infection, we capitalized on an IRES-based approach to develop a live-attenuated MAYV vaccine candidate. Testing in infant, immunocompetent as well as interferon receptor-deficient mice demonstrated a high degree of attenuation, strong induction of neutralizing antibodies, and efficacy against lethal challenge. This vaccine strain was also unable to infect mosquito cells, a major safety feature for a live vaccine derived from a mosquito-borne virus. Further preclinical development of this vaccine candidate is warranted to protect against this important emerging disease.

  1. Research progress in live attenuated Brucella vaccine development.

    Science.gov (United States)

    Wang, Zhen; Wu, Qingmin

    2013-01-01

    Brucella spp. are facultative intracellular bacteria that cause brucellosis, which is a globally occurring zoonotic disease that is characterized by abortion in domestic animals and undulant fever, arthritis, endocarditis, and meningitis in humans. There are currently no licensed vaccines against brucellosis for human use, and only a few licensed live Brucella vaccines are available for use in animals. However, the available animal vaccines may cause abortion and are associated with lower protection rates in animals and higher virulence in humans. Much research has been performed recently to develop novel Brucella vaccines for the prevention and control of animal brucellosis. This article discusses the approaches and strategies for novel live attenuated vaccine development.

  2. Measles-mumps-rubella-varicella combination vaccine (ProQuad): a guide to its use in children in the E.U.

    Science.gov (United States)

    Scott, Lesley J

    2015-04-01

    In the EU, the live attenuated, tetravalent measles-mumps-rubella-varicella vaccine ProQuad is indicated for simultaneous vaccination against measles, mumps, rubella and varicella in individuals from 12 months of age using a two-dose schedule and may be used in infants from 9 months of age to conform with a national vaccination schedule, outbreak situations or travel to a region with a high prevalence of measles. Clinical data in young children indicates that vaccination with ProQuad is as immunogenic as the component vaccines, provides long-term protection against these potentially serious childhood infections and has an acceptable safety profile. Combining the viral strains of the measles-mumps-rubella vaccine M-M-RVAXPRO and the varicella vaccine Varivax in ProQuad reduces the complexity of vaccination schedules, thereby potentially improving vaccination coverage and the timeliness of vaccination.

  3. Clinical evaluation strategies for a live attenuated tetravalent dengue vaccine.

    Science.gov (United States)

    Precioso, Alexander Roberto; Palacios, Ricardo; Thomé, Beatriz; Mondini, Gabriella; Braga, Patrícia; Kalil, Jorge

    2015-12-10

    Butantan Institute is a public Brazilian biomedical research-manufacturer center affiliated to the São Paulo State Secretary of Health. Currently, Butantan is one of the main public producers of vaccines, antivenoms, and antitoxins in Latin America. The partnership between Butantan and the National Institutes of Health (NIH) of the United Sates has been one of the longest and most successful partnerships in the development and manufacturing of new vaccines. Recently, Butantan Institute has developed and manufactured a lyophilized tetravalent live attenuated dengue vaccine with the four dengue viruses attenuated and licensed from the Laboratory of Infectious Diseases at The National Institutes of Allergy and Infectious Diseases (LID/NIAID/NIH). The objective of this paper is to describe the clinical evaluation strategies of a live attenuated tetravalent dengue vaccine (Butantan-DV) developed and manufactured by Butantan Institute. These clinical strategies will be used to evaluate the Butantan-DV Phase III trial to support the Butantan-DV licensure for protection against any symptomatic dengue caused by any serotype in people aged 2 to 59 years.

  4. Complications of Mumps

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    ... Serology Publications and Resources Multimedia MMWR Articles Outbreak Articles Related Links World Health Organization Medline Plus Complications of Mumps Language: English Español (Spanish) Recommend on Facebook Tweet Share Compartir ...

  5. Transmission of Mumps

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    ... Serology Publications and Resources Multimedia MMWR Articles Outbreak Articles Related Links World Health Organization Medline Plus Transmission of Mumps Language: English Español (Spanish) Recommend on Facebook Tweet Share Compartir ...

  6. Measles, Mumps, Rubella (MMR)

    Science.gov (United States)

    ... at Each Vaccine: MMR (Measles, Mumps and Rubella) Vaccine Children's Hospital of Philadelphia (CHOP): Learn about measles, how ... Disease Control and Prevention AAP Urges Parents to Vaccinate Children to Protect Against Measles (1/23/15) American ...

  7. Live attenuated varicella vaccine in children with leukemia in remission.

    Science.gov (United States)

    Gershon, A A; Steinberg, S; Galasso, G; Borkowsky, W; Larussa, P; Ferrara, A; Gelb, L

    1984-09-01

    One-hundred-ninety-one children with acute leukemia in remission for at least one year were immunized with 1 or more doses of live attenuated varicella vaccine. All were susceptible to varicella prior to vaccination. The only significant side effect was mild to moderate rash, seen especially in children with maintenance chemotherapy temporarily suspended for one week before and one week after vaccination. Children with rash were at some risk (10%) to transmit vaccine virus to varicella susceptibles with whom they had close contact.

  8. Immunocompetent, Immunized Male With Mumps, Complicated by Orchitis and Meningitis.

    Science.gov (United States)

    Tomich, Allison; Grubish, Lindsay; Young, Scott; Franklin, Jillian

    2015-10-01

    Mumps is a rare pathology often not encountered in the emergency department setting. It is an especially unusual finding in a fully immunized individual. We present a case of a 26-year-old Army active duty male who was evaluated in the emergency department for mumps over the course of two visits. The military population is presumed fully immunized and immunocompetent, travels widely and often lives in close quarters. This case highlights the importance for providers to consider such a disease that carries a risk of significant morbidity, and rarely, mortality. A literature review was performed evaluating mumps in the vaccinated population.

  9. Live attenuated varicella vaccine use in immunocompromised children and adults.

    Science.gov (United States)

    Gershon, A A; Steinberg, S P; Gelb, L

    1986-10-01

    Live attenuated varicella vaccine has been administered to 307 children with leukemia in remission and to 86 healthy adults. The vaccine was well tolerated and immunogenic. The major side effect in leukemic children receiving maintenance chemotherapy was development of a vaccine-associated rash. Vaccinees in whom a rash developed were potentially somewhat infectious to others about 1 month after immunization. Vaccination was not associated with an increase in the incidence of herpes zoster or in relapse of leukemia. Vaccination provided excellent protection against severe varicella. It was associated with a significant decrease in the attack rate of chickenpox following an intimate exposure to varicella-zoster virus, conferring about 80% protection in leukemic children. The cases of breakthrough varicella that occurred were mild. Thus, the vaccine may either prevent or modify varicella in high-risk individuals. It may also have use for prevention of nosocomial varicella.

  10. Improving live attenuated bacterial carriers for vaccination and therapy.

    Science.gov (United States)

    Loessner, Holger; Endmann, Anne; Leschner, Sara; Bauer, Heike; Zelmer, Andrea; zur Lage, Susanne; Westphal, Kathrin; Weiss, Siegfried

    2008-01-01

    Live attenuated bacteria are well established as vaccines. Thus, their use as carriers for prophylactic and therapeutic macromolecules is a logical consequence. Here we describe several experimental applications of bacteria to carry heterologous macromolecules into the murine host. First, Listeria monocytogenes are described that are able to transfer eukaryotic expression plasmids into host cells for gene therapy. High multiplicities of infection are still required for efficient gene transfer and we point out some of the bottlenecks that counteract a more efficient transfer and application in vivo. Then, we describe Salmonella enterica serovar Typhimurium (S. typhimurium) as an expression plasmid transfer vehicle for oral DNA vaccination of mice. We demonstrate that the stabilization of the plasmid transformants results in an improved immune response. Stabilization was achieved by replacing the origin of replication of the original high-copy-number plasmid by a low-copy-number origin. Finally, we describe Salmonella carriers for the improved expression of heterologous proteins. We introduce a system in which the plasmid is carried as a single copy during cultivation but is amplified several fold upon infection of the host. Using the same in vivo inducible promoter for both protein expression and plasmid amplification, a substantial increase in antigen expression in vivo can be achieved. A modification of this approach is the introduction of inducible gene expression in vivo with a low-molecular-weight compound. Using P(BAD) promoter and L-arabinose as inducer we were able to deliberately activate genes in the bacterial carrier. No background activity could be observed with P(BAD) such that an inducible suicide gene could be introduced. This is adding an important safety feature to such live attenuated carrier bacteria.

  11. Live attenuated vaccines: Historical successes and current challenges

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    Minor, Philip D., E-mail: Philip.Minor@nibsc.org

    2015-05-15

    Live attenuated vaccines against human viral diseases have been amongst the most successful cost effective interventions in medical history. Smallpox was declared eradicated in 1980; poliomyelitis is nearing global eradication and measles has been controlled in most parts of the world. Vaccines function well for acute diseases such as these but chronic infections such as HIV are more challenging for reasons of both likely safety and probable efficacy. The derivation of the vaccines used has in general not been purely rational except in the sense that it has involved careful clinical trials of candidates and subsequent careful follow up in clinical use; the identification of the candidates is reviewed. - Highlights: • Live vaccines against human diseases caused by viruses have been very successful. • They have been developed by empirical clinical studies and problems identified in later use. • It can be difficult to balance ability to cause disease and ability to immunise for a strain. • There is currently no reliable basis for predicting success from pure virological studies. • Vaccinia, which eradicated smallpox, is the paradigm for all successes and issues.

  12. Engineering temperature sensitive live attenuated influenza vaccines from emerging viruses.

    Science.gov (United States)

    Zhou, Bin; Li, Yan; Speer, Scott D; Subba, Anju; Lin, Xudong; Wentworth, David E

    2012-05-21

    The licensed live attenuated influenza A vaccine (LAIV) in the United States is created by making a reassortant containing six internal genes from a cold-adapted master donor strain (ca A/AA/6/60) and two surface glycoprotein genes from a circulating/emerging strain (e.g., A/CA/7/09 for the 2009/2010 H1N1 pandemic). Technologies to rapidly create recombinant viruses directly from patient specimens were used to engineer alternative LAIV candidates that have genomes composed entirely of vRNAs from pandemic or seasonal strains. Multiple mutations involved in the temperature-sensitive (ts) phenotype of the ca A/AA/6/60 master donor strain were introduced into a 2009 H1N1 pandemic strain rA/New York/1682/2009 (rNY1682-WT) to create rNY1682-TS1, and additional mutations identified in other ts viruses were added to rNY1682-TS1 to create rNY1682-TS2. Both rNY1682-TS1 and rNY1682-TS2 replicated efficiently at 30°C and 33°C. However, rNY1682-TS1 was partially restricted, and rNY1682-TS2 was completely restricted at 39°C. Additionally, engineering the TS1 or TS2 mutations into a distantly related human seasonal H1N1 influenza A virus also resulted pronounced restriction of replication in vitro. Clinical symptoms and virus replication in the lungs of mice showed that although rNY1682-TS2 and the licensed FluMist(®)-H1N1pdm LAIV that was used to combat the 2009/2010 pandemic were similarly attenuated, the rNY1682-TS2 was more protective upon challenge with a virulent mutant of pandemic H1N1 virus or a heterologous H1N1 (A/PR/8/1934) virus. This study demonstrates that engineering key temperature sensitive mutations (PB1-K391E, D581G, A661T; PB2-P112S, N265S, N556D, Y658H) into the genomes of influenza A viruses attenuates divergent human virus lineages and provides an alternative strategy for the generation of LAIVs. Copyright © 2012 Elsevier Ltd. All rights reserved.

  13. Live-attenuated measles virus vaccine targets dendritic cells and macrophages in muscle of nonhuman primates

    NARCIS (Netherlands)

    L.J. Rennick (Linda); R.D. de Vries (Rory); T.J. Carsillo (Thomas J.); K. Lemon (Ken); G. van Amerongen (Geert); M. Ludlow (Martin); D.T. Nguyen (Tien); S. Yüksel (Selma); R.J. Verbugh (Joyce); P. Haddock (Paula); S. McQuaid (Stephen); W.P. Duprex (Paul); R.L. de Swart (Rik)

    2015-01-01

    textabstractAlthough live-attenuated measles virus (MV) vaccines have been used successfully for over 50 years, the target cells that sustain virus replication in vivo are still unknown. We generated a reverse genetics system for the live-attenuated MV vaccine strain Edmonston- Zagreb (EZ), allowing

  14. Live-attenuated measles virus vaccine targets dendritic cells and macrophages in muscle of nonhuman primates

    NARCIS (Netherlands)

    L.J. Rennick (Linda); R.D. de Vries (Rory); T.J. Carsillo (Thomas J.); K. Lemon (Ken); G. van Amerongen (Geert); M. Ludlow (Martin); D.T. Nguyen (Tien); S. Yüksel (Selma); R.J. Verbugh (Joyce); P. Haddock (Paula); S. McQuaid (Stephen); W.P. Duprex (Paul); R.L. de Swart (Rik)

    2015-01-01

    textabstractAlthough live-attenuated measles virus (MV) vaccines have been used successfully for over 50 years, the target cells that sustain virus replication in vivo are still unknown. We generated a reverse genetics system for the live-attenuated MV vaccine strain Edmonston- Zagreb (EZ), allowing

  15. SENSORY HEARING LOSS IN CHILDREN WITH MUMPS WITH MUMPS INFECTION

    Directory of Open Access Journals (Sweden)

    S. Noorbaksh MD

    2009-04-01

    Full Text Available Objective:Mumps infection is endemic in Iran and mumps parotiditis is a common disease in Iranian children. There has been a dramatic decrease in the worldwide incidence of mumps since the introduction and use in 1968 of the very effective and inexpensive mumps vaccine.In Iran probably due to a higher percentage of unvaccinated young persons Material& Methods:This descriptive case-series study was conducted in 94children, aged less than 14 years,  hospitalized between 1999 and 2001, in the pediatric ward of the Hazrat Rasool Hospital in Tehran. All patients with documented mumps infection (specific mumps-IgM antibody were evaluated twice for audiometeric function on the basis of diagnostic parameters for sensory neural hearing loss; the first evaluation was done on admission and the second three weeks later. 54 patients (age range 1-14y, mean age 4.83±3.93, male: female ratio30:24 were studied in two years.Results:The highest incidence of mumps was seen in winter (37% and spring (28% and the lowest in summer (13%. Specific IgM antibody for mumps virus was detected in 74 children. Comprehensive audiologic evaluation was done in 54 patients at admission and again 3 weeks later. SNHL was detected in 7.2% of patients; the 4.4% incidence of SNHL in this study was higher than in other studies in developed countries prior to comprehensive vaccination programs.Conclusion:Implementation of comprehensive vaccination programs in young Iranians could dramatically reduce the burden and costs imposed by the infection and its sequelae.Keywords: Mumps infection ;SNLH(sensorineural hearing loss;Mumps vaccination

  16. Live attenuated S. Typhimurium vaccine with improved safety in immuno-compromised mice.

    Directory of Open Access Journals (Sweden)

    Balamurugan Periaswamy

    Full Text Available Live attenuated vaccines are of great value for preventing infectious diseases. They represent a delicate compromise between sufficient colonization-mediated adaptive immunity and minimizing the risk for infection by the vaccine strain itself. Immune defects can predispose to vaccine strain infections. It has remained unclear whether vaccine safety could be improved via mutations attenuating a vaccine in immune-deficient individuals without compromising the vaccine's performance in the normal host. We have addressed this hypothesis using a mouse model for Salmonella diarrhea and a live attenuated Salmonella Typhimurium strain (ssaV. Vaccination with this strain elicited protective immunity in wild type mice, but a fatal systemic infection in immune-deficient cybb(-/-nos2(-/- animals lacking NADPH oxidase and inducible NO synthase. In cybb(-/-nos2(-/- mice, we analyzed the attenuation of 35 ssaV strains carrying one additional mutation each. One strain, Z234 (ssaV SL1344_3093, was >1000-fold attenuated in cybb(-/-nos2(-/- mice and ≈100 fold attenuated in tnfr1(-/- animals. However, in wt mice, Z234 was as efficient as ssaV with respect to host colonization and the elicitation of a protective, O-antigen specific mucosal secretory IgA (sIgA response. These data suggest that it is possible to engineer live attenuated vaccines which are specifically attenuated in immuno-compromised hosts. This might help to improve vaccine safety.

  17. Mumps: a resurgent disease with protean manifestations.

    Science.gov (United States)

    Senanayake, Sanjaya N

    2008-10-20

    Mumps has re-emerged as an infection in the developed world. Its epidemiology has changed, with the majority of cases now primarily affecting adolescents and adults. While mumps is easily suspected if parotitis is present, parotitis is absent in 10%-30% of symptomatic cases. Mumps is a systemic infection with a variety of extra-parotid complications. In Australia, mumps diagnosis is confirmed by antibody testing and reverse transcriptase-polymerase chain reaction techniques. Suitable specimens for testing are serum, saliva, urine and cerebrospinal fluid. Treatment is generally supportive, although intravenous immunoglobulin therapy may have a future role in mumps management. Interferon alpha-2b treatment may be considered specifically for mumps epididymo-orchitis. Mumps vaccine is included in the measles-mumps-rubella (MMR) vaccine. In Australia, this vaccine is routinely administered at the ages of 1 and 4 years. Serious reactions to the mumps components of the MMR vaccine are rare.

  18. Using recombinant DNA technology for the development of live-attenuated dengue vaccines.

    Science.gov (United States)

    Lee, Hsiang-Chi; Butler, Michael; Wu, Suh-Chin

    2012-07-15

    Dramatic increases in dengue (DEN) incidence and disease severity have been reported, in great part due to the geographic expansion of Aedes aegypti and Aedes albopictus mosquitoes. One result is the expanded co-circulation of all dengue 1-4 serotype viruses (DENV) in urban areas worldwide, especially in South and South-East Asia, and South America. DEN disease severity ranges from asymptomatic infections to febrile dengue fevers (DF) to life-threatening dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). There is an urgent need for a safe and effective tetravalent DEN vaccine. Several live attenuated, tetravalent DEN vaccine candidates have been generated by recombinant DNA technology; these candidates are capable of providing immunity to all four DENV serotypes. In this paper we review (a) recombinant live-attenuated DEN vaccine candidates in terms of deletion, antigen chimerization, and the introduction of adaptive mutations; (b) strategies for improving tetravalent vaccine attenuation; and (c) live-attenuated DENV vaccine development.

  19. Immunization with Eimeria ninakohlyakimovae-live attenuated oocysts protect goat kids from clinical coccidiosis.

    Science.gov (United States)

    Ruiz, Antonio; Muñoz, María Carmen; Molina, José Manuel; Hermosilla, Carlos; Andrada, Marisa; Lara, Pedro; Bordón, Elisa; Pérez, Davinia; López, Adassa María; Matos, Lorena; Guedes, Aránzazu Carmen; Falcón, Soraya; Falcón, Yaiza; Martín, Sergio; Taubert, Anja

    2014-01-17

    Caprine coccidiosis, affecting mainly young goat kids around the weaning period, is worldwide the most important disease in the goat industry. Control of caprine coccidiosis is increasingly hampered by resistances developed against coccidiostatic drugs leading to an enhanced need for anticoccidial vaccines. In the current study we conducted an oral immunization trial with live attenuated sporulated Eimeria ninakohlyakimovae oocysts. Sporulated E. ninakohlyakimovae oocysts were attenuated by X-irradiation technique. The experimental design included a total of 18 goat kids divided into the following groups: (i) animals immunized with attenuated E. ninakohlyakimovae oocysts at 5 weeks of age and challenged 3 weeks later with non-irradiated homologous oocysts (group 1); (ii) animals infected with non-attenuated E. ninakohlyakimovae oocysts at 5 weeks of age and challenged 3 weeks later with non-attenuated homologous oocysts (group 2); (iii) animals primary-infected with untreated E. ninakohlyakimovae oocysts at 8 weeks of age (control of the challenge infection, group 3); (iv) non-infected control animals (group 4). Goat kids immunized with live attenuated E. ninakohlyakimovae oocysts (group 1) excreted significantly less oocysts in the faeces (95.3% reduction) than kids infected with non-attenuated ones (group 2). Furthermore, immunization with live but attenuated oocysts resulted in ameliorated clinical coccidiosis compared to goat kids infected with untreated oocysts (group 2) and resulted in equally reduced signs of coccidiosis after challenge infection compared to acquired immunity driven by non-attenuated oocysts. Overall, the present study demonstrates for the first time that live attenuated E. ninakohlyakimovae oocysts orally administered showed almost no pathogenicity but enough immunogenicity in terms of immunoprotection. Importantly, vaccinated animals still shed low amounts of oocysts, guaranteeing environmental contamination and consecutive booster

  20. Signs and Symptoms of Mumps

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    ... Serology Publications and Resources Multimedia MMWR Articles Outbreak Articles Related Links World Health Organization Medline Plus Signs & Symptoms of Mumps Language: English Español (Spanish) Recommend on Facebook Tweet Share Compartir ...

  1. Effect of jet injection on infectivity of measles, mumps, and rubella vaccine in a bench model.

    Science.gov (United States)

    Coughlin, Melissa M; Collins, Marcus; Saxon, Gene; Jarrahian, Courtney; Zehrung, Darin; Cappello, Chris; Dhere, Rajeev; Royals, Michael; Papania, Mark; Rota, Paul A

    2015-08-26

    Disposable-syringe jet injectors (DSJIs) with single-use, auto disable, needle-free syringes offer the opportunity to avoid hazards associated with injection using a needle and syringe. Clinical studies have evaluated DSJIs for vaccine delivery, but most studies have focused on inactivated, subunit, or DNA vaccines. Questions have been raised about possible damage to live attenuated viral vaccines by forces generated during the jet injection process. This study examines the effect of jet injection on the integrity of measles, mumps, and rubella vaccine (MMR), measured by viral RNA content and infectivity. Three models of DSJIs were evaluated, each generating a different ejection force. Following jet injection, the RNA content for each of the vaccine components was measured using RT-qPCR immediately after injection and following passage in Vero cells. Jet injection was performed with and without pig skin as a simulation of human skin. There was little to no reduction of RNA content immediately following jet injection with any of the three DSJIs. Samples passaged in Vero cells showed no loss in infectivity of the measles vaccine following jet injection. Mumps vaccine consistently showed increased replication following jet injection. Rubella vaccine showed no loss after jet injection alone but some infectivity loss following injection through pig skin with two of the devices. Overall, these data demonstrated that forces exerted on a live attenuated MMR vaccine did not compromise vaccine infectivity. The bench model and protocol used in this study can be applied to evaluate the impact of jet injection on other live virus vaccines.

  2. Development of live attenuated sparfloxacin-resistant Streptococcus agalactiae polyvalent vaccines to protect Nile tilapia

    Science.gov (United States)

    To develop attenuated bacteria as potential live vaccines, sparfloxacin was used in this study to modify 40 isolates of Streptococcus agalactiae. Majority of S. agalactiae used in this study were able to develop at least 80-fold resistance to sparfloxacin. When the virulence of the sparfloxacin-resi...

  3. Antibody Response in Seropositive Multiple Sclerosis Patients Vaccinated with Attenuated Live Varicella Zoster Virus

    Directory of Open Access Journals (Sweden)

    RT Ross

    1996-01-01

    Full Text Available OBJECTIVE: To determine the safety and effectiveness of live attenuated varicella zoster virus (VZV vaccine (OKA/Merck on 50 patients with chronic progressive multiple sclerosis (MS, based on the hypothesis that VZV might be the antigen or antigen mimic of MS plus the fact that repeated high antigen doses have produced ‘antigen paralysis’ in experimental allergic encephalomyelitis mice.

  4. Development of live attenuated Streptococcus agalactiae as potential vaccines by selecting for resistance to sparfloxacin

    Science.gov (United States)

    To develop attenuated bacteria as potential live vaccines, sparfloxacin was used in this study to modify 40 isolates of Streptococcus agalactiae. Majority of S. agalactiae used in this study were able to develop at least 80-fold resistance to sparfloxacin. When the virulence of the sparfloxacin-resi...

  5. Mumps encephalitis with akinesia and mutism.

    Science.gov (United States)

    Suga, Kenichi; Goji, Aya; Shono, Miki; Matsuura, Sato; Inoue, Miki; Toda, Eiko; Miyazaki, Tatsushi; Kawahito, Masami; Mori, Kazuhiro

    2015-08-01

    Measles-rubella-mumps vaccination is routine in many countries, but the mumps vaccine remains voluntary and is not covered by insurance in Japan. A 5-year-old Japanese boy who had not received the mumps vaccine was affected by mumps parotitis. Several days later, he presented with various neurological abnormalities, including akinesia, mutism, dysphagia, and uncontrolled respiratory disorder. Mumps encephalitis was diagnosed. Despite steroid pulse and immunoglobulin treatment, the disease progressed. Magnetic resonance imaging showed necrotic changes in bilateral basal ganglia, midbrain, and hypothalamus. At 1 year follow up, he was bedridden and required enteral feeding through a gastric fistula and tracheostomy. Mumps vaccination should be made routine as soon as possible in Japan, because mumps encephalitis carries the risk of severe sequelae. © 2015 Japan Pediatric Society.

  6. Immunogenicity and safety of live attenuated hepatitis A vaccine (Biovac-A™ in healthy Indian children

    Directory of Open Access Journals (Sweden)

    Bhave S

    2013-12-01

    Full Text Available Sheila Bhave,1 Apurba Ghosh,2 Amita Sapru,1 Monjori Mitra,2 Suparna Chatterjee,3 Nisha Bhattacharya,2 Ganesh Kadhe,4 Amey Mane,4 Sucheta Roy41Department of Pediatrics, KEM Hospital Research Centre, Pune, Maharashtra, India; 2Department of Pediatrics, Institute of Child Health, Kolkata, West Bengal, India; 3Institute of Post Graduate Medical Education & Research, Kolkata, West Bengal, India; 4Medical Affairs Department, Wockhardt Ltd, Mumbai, IndiaIntroduction: The World Health Organization (WHO recommends either inactivated or live attenuated vaccine against the hepatitis A virus (HAV infection in countries with high incidence. Live attenuated vaccines against HAV infection have been developed and used exclusively in the People’s Republic of China and have shown promising results. This is the first study conducted outside the People’s Republic of China to evaluate the immunogenicity and safety of live attenuated hepatitis A vaccine (Biovac-A™ in healthy Indian children.Material and methods: This was an open-labeled, 8-week (July 2012 to October 2012, non-comparative, non-randomized, confirmatory study conducted at two centers (Kolkata and Pune in India. A total of 140 healthy Indian children aged 12 months to 12 years were administered live attenuated hepatitis A vaccine at the two centers. Overall, 137 subjects (female: 66, mean age: 4.09±2.5 years completed the study. The subjects were vaccinated (subcutaneous over the deltoid muscle of the upper arm with 0.5 mL of live attenuated H2 strain hepatitis A vaccine.Results: Eight weeks after a single dose of the vaccine, 136 subjects from both the centers developed protective immunoglobulin (IgM G antibodies ≥20 mIU/mL. The overall seroconversion rate was 99% (Kolkata: 100%, Pune: 98%. The hematological and biochemical parameters remained within normal limits. All the adverse events were non-serious and mild in severity.Conclusion: Live attenuated H2 strain hepatitis A vaccine is

  7. VACCINATION OF PATIENTS WITH ONCOLOGY DISEASES AGAINST MEASLES AND MUMPS

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    S. M. Kharit

    2011-01-01

    Full Text Available Abstract. One hundred and seven children (45 girls and 62 boys in the age of 20 months — 14 years old (mean 9,62±0,37 suffered from acute lymphoblast leukosis and solid tumors in history have been examined in the clinic of Research Institute of children infections of FMBA. The vaccination history was studied in all children and the titers of specific antibodies to measles and mumps viruses as well as immune status were determined. 83,8% and 85,4% of studied children had no protection against measles and mumps respectively or had low titers of antibodies. Immunological examination of these children conducted within 4 months after finishing of therapy revealed absence of immunodeficiency. It gave opportunities to vaccinate or revaccinate these children against mentioned infections. Fifty three children were immunized against measles and 47 — against mumps. Application of live vaccines was safe because majority of vaccinated against measles (81,1% and mumps (82,9% children had mild vaccination process. It was established that to increase immunological efficacy of vaccination using of polyoxidony during 5 days before vaccination and 5 days after vaccination is reasonable.

  8. Comparative genomics of the Mycobacterium signaling architecture and implications for a novel live attenuated Tuberculosis vaccine.

    Science.gov (United States)

    Zhou, Peifu; Xie, Jianping

    2014-01-01

    Tuberculosis (TB), caused by Mycobacterium tuberculosis (M.tb), remains a major threat to global public health. A new TB vaccine affording superior immune protection to M. bovis Bacillus Calmette-Guérin (BCG) is imperative. The advantage of a live attenuated vaccine is that it can mimic the bona fide pathogen, elicit immune responses similar to natural infection, and potentially provide more protection than other vaccines. BCG, the only vaccine and a live attenuated vaccine that is the result of cumulative mutations by serial passage of M. bovis, has provided clues for the construction of novel improved vaccines. A strategy is put forward for identifying a new live attenuated TB vaccine generated by cumulative mutation based on M.tb. Given the important role of the M.tb signaling network consisting of a two-component system, eukaryotic-like Ser/Thr protein kinase system and sigma factor system based on comparisons among M.tb H37Rv, M. bovis, and BCG, we have put a premium on this signaling circuit as the starting point for the generation of an attenuated TB vaccine.

  9. Envelope exchange for the generation of live-attenuated arenavirus vaccines.

    Directory of Open Access Journals (Sweden)

    Andreas Bergthaler

    2006-06-01

    Full Text Available Arenaviruses such as Lassa fever virus cause significant mortality in endemic areas and represent potential bioterrorist weapons. The occurrence of arenaviral hemorrhagic fevers is largely confined to Third World countries with a limited medical infrastructure, and therefore live-attenuated vaccines have long been sought as a method of choice for prevention. Yet their rational design and engineering have been thwarted by technical limitations. In addition, viral genes had not been identified that are needed to cause disease but can be deleted or substituted to generate live-attenuated vaccine strains. Lymphocytic choriomeningitis virus, the prototype arenavirus, induces cell-mediated immunity against Lassa fever virus, but its safety for humans is unclear and untested. Using this virus model, we have developed the necessary methodology to efficiently modify arenavirus genomes and have exploited these techniques to identify an arenaviral Achilles' heel suitable for targeting in vaccine design. Reverse genetic exchange of the viral glycoprotein for foreign glycoproteins created attenuated vaccine strains that remained viable although unable to cause disease in infected mice. This phenotype remained stable even after extensive propagation in immunodeficient hosts. Nevertheless, the engineered viruses induced T cell-mediated immunity protecting against overwhelming systemic infection and severe liver disease upon wild-type virus challenge. Protection was established within 3 to 7 d after immunization and lasted for approximately 300 d. The identification of an arenaviral Achilles' heel demonstrates that the reverse genetic engineering of live-attenuated arenavirus vaccines is feasible. Moreover, our findings offer lymphocytic choriomeningitis virus or other arenaviruses expressing foreign glycoproteins as promising live-attenuated arenavirus vaccine candidates.

  10. Envelope Exchange for the Generation of Live-Attenuated Arenavirus Vaccines.

    Directory of Open Access Journals (Sweden)

    2006-06-01

    Full Text Available Arenaviruses such as Lassa fever virus cause significant mortality in endemic areas and represent potential bioterrorist weapons. The occurrence of arenaviral hemorrhagic fevers is largely confined to Third World countries with a limited medical infrastructure, and therefore live-attenuated vaccines have long been sought as a method of choice for prevention. Yet their rational design and engineering have been thwarted by technical limitations. In addition, viral genes had not been identified that are needed to cause disease but can be deleted or substituted to generate live-attenuated vaccine strains. Lymphocytic choriomeningitis virus, the prototype arenavirus, induces cell-mediated immunity against Lassa fever virus, but its safety for humans is unclear and untested. Using this virus model, we have developed the necessary methodology to efficiently modify arenavirus genomes and have exploited these techniques to identify an arenaviral Achilles' heel suitable for targeting in vaccine design. Reverse genetic exchange of the viral glycoprotein for foreign glycoproteins created attenuated vaccine strains that remained viable although unable to cause disease in infected mice. This phenotype remained stable even after extensive propagation in immunodeficient hosts. Nevertheless, the engineered viruses induced T cell-mediated immunity protecting against overwhelming systemic infection and severe liver disease upon wild-type virus challenge. Protection was established within 3 to 7 d after immunization and lasted for approximately 300 d. The identification of an arenaviral Achilles' heel demonstrates that the reverse genetic engineering of live-attenuated arenavirus vaccines is feasible. Moreover, our findings offer lymphocytic choriomeningitis virus or other arenaviruses expressing foreign glycoproteins as promising live-attenuated arenavirus vaccine candidates.

  11. The Case for Live Attenuated Vaccines against the Neglected Zoonotic Diseases Brucellosis and Bovine Tuberculosis

    Science.gov (United States)

    Pandey, Aseem; Cabello, Ana; Akoolo, Lavoisier; Rice-Ficht, Allison; Arenas-Gamboa, Angela; McMurray, David; Ficht, Thomas A.; de Figueiredo, Paul

    2016-01-01

    Vaccination of humans and animals with live attenuated organisms has proven to be an effective means of combatting some important infectious diseases. In fact, the 20th century witnessed tremendous improvements in human and animal health worldwide as a consequence of large-scale vaccination programs with live attenuated vaccines (LAVs). Here, we use the neglected zoonotic diseases brucellosis and bovine tuberculosis (BTb) caused by Brucella spp. and Mycobacterium bovis (M. bovis), respectively, as comparative models to outline the merits of LAV platforms with emphasis on molecular strategies that have been pursued to generate LAVs with enhanced vaccine safety and efficacy profiles. Finally, we discuss the prospects of LAV platforms in the fight against brucellosis and BTb and outline new avenues for future research towards developing effective vaccines using LAV platforms. PMID:27537413

  12. An Overview of Live Attenuated Recombinant Pseudorabies Viruses for Use as Novel Vaccines

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    Bo Dong

    2014-01-01

    Full Text Available Pseudorabies virus (PRV is a double-stranded, DNA-based swine virus with a genome approximating 150 kb in size. PRV has many nonessential genes which can be replaced with genes encoding heterologous antigens but without deleterious effects on virus propagation. Recombinant PRVs expressing both native and foreign antigens are able to stimulate immune responses. In this paper, we review the current status of live attenuated recombinant PRVs and live PRV-based vector vaccines with potential for controlling viral infections in animals.

  13. Herpes Simplex Vaccines: Prospects of Live-attenuated HSV Vaccines to Combat Genital and Ocular infections

    Science.gov (United States)

    Stanfield, Brent; Kousoulas, Konstantin Gus

    2015-01-01

    Herpes simplex virus type-1 (HSV-1) and its closely related type-2 (HSV-2) viruses cause important clinical manifestations in humans including acute ocular disease and genital infections. These viruses establish latency in the trigeminal ganglionic and dorsal root neurons, respectively. Both viruses are widespread among humans and can frequently reactivate from latency causing disease. Currently, there are no vaccines available against herpes simplex viral infections. However, a number of promising vaccine approaches are being explored in pre-clinical investigations with few progressing to early phase clinical trials. Consensus research findings suggest that robust humoral and cellular immune responses may partially control the frequency of reactivation episodes and reduce clinical symptoms. Live-attenuated viral vaccines have long been considered as a viable option for generating robust and protective immune responses against viral pathogens. Varicella zoster virus (VZV) belongs to the same alphaherpesvirus subfamily with herpes simplex viruses. A live-attenuated VZV vaccine has been extensively used in a prophylactic and therapeutic approach to combat primary and recurrent VZV infection indicating that a similar vaccine approach may be feasible for HSVs. In this review, we summarize pre-clinical approaches to HSV vaccine development and current efforts to test certain vaccine approaches in human clinical trials. Also, we discuss the potential advantages of using a safe, live-attenuated HSV-1 vaccine strain to protect against both HSV-1 and HSV-2 infections. PMID:27114893

  14. Live-Attenuated Bacterial Vectors: Tools for Vaccine and Therapeutic Agent Delivery

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    Ivan Y. C. Lin

    2015-11-01

    Full Text Available Genetically attenuated microorganisms, including pathogenic and commensal bacteria, can be engineered to carry and deliver heterologous antigens to elicit host immunity against both the vector as well as the pathogen from which the donor gene is derived. These live attenuated bacterial vectors have been given much attention due to their capacity to induce a broad range of immune responses including localized mucosal, as well as systemic humoral and/or cell-mediated immunity. In addition, the unique tumor-homing characteristics of these bacterial vectors has also been exploited for alternative anti-tumor vaccines and therapies. In such approach, tumor-associated antigen, immunostimulatory molecules, anti-tumor drugs, or nucleotides (DNA or RNA are delivered. Different potential vectors are appropriate for specific applications, depending on their pathogenic routes. In this review, we survey and summarize the main features of the different types of live bacterial vectors and discussed the clinical applications in the field of vaccinology. In addition, different approaches for using live attenuated bacterial vectors for anti-cancer therapy is discussed, and some promising pre-clinical and clinical studies in this field are outlined.

  15. Mumps Seroprevalence in not Vaccinated Children Aged Between 0-59 Months in Adana

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    Akgun Yaman

    2010-02-01

    Full Text Available AIM: This study aims to find out the mumps seroprevalence in 0-59 month old children who were not vaccinated for mumps in the duty area of Dogankent Health Center where people of low socio-economic level lives. METHOD: A cross-sectional study was made on 331 children aged between 0-59 months who were not vaccinated with rubella vaccine. RESULTS: Mumps seropositivity was found as 35.3%. Mumps seropositivity was significantly high in 24-35 month old boys, and fathers who haven’t incame/occupation (p0.05. CONCLUSION: In the present study, mumps seropositivity is low in children aged 0- 59 months. In order to eradicate mumps, it is necessary that use of MMR vaccine should be expanded nationwide rapidly by the Ministry of Health; the regulation should be revised to include the children born before 2005. [TAF Prev Med Bull 2010; 9(1.000: 29-36

  16. Immunogenicity and protective efficacy of a live attenuated H5N1 vaccine in nonhuman primates.

    Directory of Open Access Journals (Sweden)

    Shufang Fan

    2009-05-01

    Full Text Available The continued spread of highly pathogenic H5N1 influenza viruses among poultry and wild birds, together with the emergence of drug-resistant variants and the possibility of human-to-human transmission, has spurred attempts to develop an effective vaccine. Inactivated subvirion or whole-virion H5N1 vaccines have shown promising immunogenicity in clinical trials, but their ability to elicit protective immunity in unprimed human populations remains unknown. A cold-adapted, live attenuated vaccine with the hemagglutinin (HA and neuraminidase (NA genes of an H5N1 virus A/VN/1203/2004 (clade 1 was protective against the pulmonary replication of homologous and heterologous wild-type H5N1 viruses in mice and ferrets. In this study, we used reverse genetics to produce a cold-adapted, live attenuated H5N1 vaccine (AH/AAca that contains HA and NA genes from a recent H5N1 isolate, A/Anhui/2/05 virus (AH/05 (clade 2.3, and the backbone of the cold-adapted influenza H2N2 A/AnnArbor/6/60 virus (AAca. AH/AAca was attenuated in chickens, mice, and monkeys, and it induced robust neutralizing antibody responses as well as HA-specific CD4+ T cell immune responses in rhesus macaques immunized twice intranasally. Importantly, the vaccinated macaques were fully protected from challenge with either the homologous AH/05 virus or a heterologous H5N1 virus, A/bar-headed goose/Qinghai/3/05 (BHG/05; clade 2.2. These results demonstrate for the first time that a cold-adapted H5N1 vaccine can elicit protective immunity against highly pathogenic H5N1 virus infection in a nonhuman primate model and provide a compelling argument for further testing of double immunization with live attenuated H5N1 vaccines in human trials.

  17. Safety, tolerability, and immunogenicity of a recombinant, genetically engineered, live-attenuated vaccine against canine blastomycosis.

    Science.gov (United States)

    Wüthrich, Marcel; Krajaejun, Theerapong; Shearn-Bochsler, Valerie; Bass, Chris; Filutowicz, Hanna I; Legendre, Alfred M; Klein, Bruce S

    2011-05-01

    Blastomycosis is a severe, commonly fatal infection caused by the dimorphic fungus Blastomyces dermatitidis in dogs that live in the United States, Canada, and parts of Africa. The cost of treating an infection can be expensive, and no vaccine against this infection is commercially available. A genetically engineered live-attenuated strain of B. dermatitidis lacking the major virulence factor BAD-1 successfully vaccinates against lethal experimental infection in mice. Here we studied the safety, toxicity, and immunogenicity of this strain as a vaccine in dogs, using 25 beagles at a teaching laboratory and 78 foxhounds in a field trial. In the beagles, escalating doses of live vaccine ranging from 2 × 10⁴ to 2 × 10⁷ yeast cells given subcutaneously were safe and did not disseminate to the lung or induce systemic illness, but a dose of vaccine dose of 10⁵ yeast cells was also well tolerated in vaccinated foxhounds who had never had blastomycosis; however, vaccinated dogs with prior infection had more local reactions at the vaccine site. The draining lymph node cells and peripheral blood lymphocytes from vaccinated dogs demonstrated gamma interferon (IFN-γ), tumor necrosis factor alpha (TNF-α), and granulocyte-macrophage colony-stimulating factor (GM-CSF) specifically in response to stimulation with Blastomyces antigens. Thus, the live-attenuated vaccine against blastomycosis studied here proved safe, well tolerated, and immunogenic in dogs and merits further studies of vaccine efficacy.

  18. Purification of mumps virus particles of high viability.

    Science.gov (United States)

    Chen, Huosheng; Ngo, Laurie; Petrovskaya, Svetlana; Gao, Yamei; Laassri, Majid; Rubin, Steven

    2016-07-01

    Mumps is a highly infectious viral disease of humans with a wide array of clinical manifestations ranging from painful swelling of the salivary glands to meningitis and encephalitis. Despite the clinical importance of mumps virus, most of what is known of its biological properties comes from studies using supernatants from virus infected cell cultures, which contain substantial levels of host cell derived debris and biologically active substances such as cytokines, transcription factors and secreted virus proteins. These contaminants complicate interpretation of studies of virus replication, virus-host interactions and in vivo virulence. Here we describe a protocol for concentration of the virus from cell culture supernatants followed by gradient purification, resulting in attainment of high titer live virus of high purity.

  19. Immunogenicity of a Live Attenuated Chimeric Japanese Encephalitis Vaccine as a Booster Dose After Primary Vaccination With Live Attenuated SA14-14-2 Vaccine: A Phase IV Study in Thai Children.

    Science.gov (United States)

    Sricharoenchai, Sirintip; Lapphra, Keswadee; Chuenkitmongkol, Sunate; Phongsamart, Wanatpreeya; Bouckenooghe, Alain; Wittawatmongkol, Orasri; Rungmaitree, Supattra; Chokephaibulkit, Kulkanya

    2017-02-01

    This single-group study investigated the immunogenicity and safety of a booster dose of the recently licensed live attenuated chimeric Japanese encephalitis vaccine in 50 healthy children (1-5 years old) who were primed with the live attenuated SA14-14-2 vaccine. A strong anamnestic response was induced 28 days postbooster: geometric mean titer, 9144 (95% confidence interval: 7365-11353); and seroprotection rate, 49 of 49 (100%) children.

  20. Research Regarding some Live Attenuated Vaccines Used in Immunoprophylaxis of the Avian Infectious Bursitis

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    Emil Tirziu

    2010-10-01

    Full Text Available In our research four live attenuated vaccines against avian infectious bursitis (two inland produced and two imported were tested: Biavac, Biaromvac-Pa, Gumboro Vaccine Nobilis 228e and Live Virus Vaccine Tablets Gumboro, M.B. Strain. The research was made in production conditions on 44,400 broiler chickens maintained in industrial system and raised on bedding and in batteries. The broilers were kept in four poultry houses, each of them representing an experimental group. We mention that vaccines were administered only one time. Vaccines efficiency was assessed by immunoenzymatic test. In that purpose, for each poultry house, 20 broilers were isolated and identified by a tibial ring, their immune response being followed between 5 and 42 days of age. Analyzing the results about individual antibodies titer during the experiment, the significant differences were observed both in poultries and phases. The best results were obtained using Live Virus Vaccine Tablets Gumboro, M.B. strain.

  1. Immunization with a live attenuated H7N9 influenza vaccine protects mice against lethal challenge.

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    Xiaolan Yang

    Full Text Available The emergence of severe cases of human influenza A (H7N9 viral infection in China in the spring of 2003 resulted in a global effort to rapidly develop an effective candidate vaccine. In this study, a cold-adapted (ca, live attenuated monovalent reassortant influenza H7N9 virus (Ah01/AA ca was generated using reverse genetics that contained hemagglutinin (HA and neuraminidase (NA genes from a 2013 pandemic A H7N9 isolate, A/Anhui/01/2013 virus (Ah01/H7N9; the remaining six backbone genes derived from the cold-adapted influenza H2N2 A/Ann Arbor/6/60 virus (AA virus. Ah01/AA ca virus exhibited temperature sensitivity (ts, ca, and attenuation (att phenotypes. Intranasal immunization of female BALB/c mice with Ah01/AA ca twice at a 2-week interval induced robust humoral, mucosal, and cell-mediated immune responses in a dose-dependent manner. Furthermore, the candidate Ah01/AA ca virus was immunogenic and offered partial or complete protection of mice against a lethal challenge by the live 2013 influenza A H7N9 (A/Anhui/01/2013. Protection was demonstrated by the inhibition of viral replication and the attenuation of histopathological changes in the challenged mouse lung. Taken together, these data support the further evaluation of this Ah01/AA ca candidate vaccine in primates.

  2. Development of live-attenuated arenavirus vaccines based on codon deoptimization of the viral glycoprotein.

    Science.gov (United States)

    Cheng, Benson Y H; Nogales, Aitor; de la Torre, Juan Carlos; Martínez-Sobrido, Luis

    2017-01-15

    Several arenaviruses, chiefly Lassa (LASV) in West Africa, cause hemorrhagic fever (HF) disease in humans and pose important public health problems in their endemic regions. To date, there are no FDA-approved arenavirus vaccines and current anti-arenaviral therapy is limited to the use of ribavirin that has very limited efficacy. In this work we document that a recombinant prototypic arenavirus lymphocytic choriomeningitis virus (LCMV) with a codon deoptimized (CD) surface glycoprotein (GP), rLCMV/CD, exhibited wild type (WT)-like growth properties in cultured cells despite barely detectable GP expression levels in rLCMV/CD-infected cells. Importantly, rLCMV/CD was highly attenuated in vivo but able to induce complete protection against a subsequent lethal challenge with rLCMV/WT. Our findings support the feasibility of implementing an arenavirus GP CD-based approach for the development of safe and effective live-attenuated vaccines (LAVs) to combat diseases caused by human pathogenic arenaviruses.

  3. Duration of protective immunity after a single vaccination with a live attenuated bivalent bluetongue vaccine.

    Science.gov (United States)

    Zhugunissov, Kuandyk; Yershebulov, Zakir; Barakbayev, Kainar; Bulatov, Yerbol; Taranov, Dmitriy; Amanova, Zhanat; Abduraimov, Yergali

    2015-12-01

    The prevention of bluetongue is typically achieved with mono- or polyvalent modified- live-attenuated virus (MLV) vaccines. MLV vaccines typically elicit a strong antibody response that correlates directly with their ability to replicate in the vaccinated animal. They are inexpensive, stimulate protective immunity after a single inoculation, and have been proven effective in preventing clinical bluetongue disease. In this study, we evaluated the safety, immunogenicity, and efficacy of a bluetongue vaccine against Bluetongue virus serotypes 4 and 16 in sheep. All the animals remained clinically healthy during the observation period. The vaccinated animals showed no clinical signs except fever (>40.8 °C) for 2-4 days. Rapid seroconversion was observed in the sheep, with the accumulation of high antibody titers in the vaccinated animals. No animal became ill after the challenge, indicating that effective protection was achieved. Therefore, this vaccine, prepared from attenuated bluetongue virus strains, is safe, immunogenic, and efficacious.

  4. Case of mumps orchitis after vaccination.

    Science.gov (United States)

    Kanda, Takayoshi; Mochida, Junichi; Takada, Shogo; Hori, Yutaro; Yamaguchi, Kenya; Takahashi, Satoru

    2014-04-01

    We present a case of mumps orchitis after vaccination. A 35-year-old man visited the emergency unit of our hospital for fever and right testicular pain on 7 January 2012. Two weeks before the visit, he underwent vaccination for mumps. After 7 days of hospitalization, the patient recovered from fever and testicular pain. Scrotal magnetic resonance imaging suggested right orchitis, and an increased level of serum mumps immunoglobulin M and immunoglobulin G indicated an initial infection of mumps virus. The peak value of immunoglobulin G showed 106 enzyme immunoassay unit 5 weeks after vaccination, which was 10-fold higher than the ordinary rise of a vaccinated individual. This fact leads to two possibilities. One is this happened as an adverse event of vaccination, and the other is that he actually had a wild-type infection at the same time as vaccination. There are some reports regarding adverse events of mumps vaccine; however, they might include wild-type infection.

  5. Measles-mumps-rubella vaccination and respiratory syncytial virus-associated hospital contact

    DEFF Research Database (Denmark)

    Benn, Christine Stabell; Sørup, Signe; Stensballe, Lone Graff

    2015-01-01

    BACKGROUND: The live measles vaccine has been associated with lower non-measles mortality and admissions in low-income countries. The live measles-mumps-rubella vaccine has also been associated with lower rate of admissions with any type of infection in Danish children; the association...... was strongest for admissions with lower respiratory infections. OBJECTIVE: To examine whether measles, mumps, and rubella (MMR) vaccination was associated with reduced rate of hospital contact related to respiratory syncytial virus (RSV) in a high-income country. METHODS: Nationwide cohort study of laboratory...

  6. In vitro evaluation of live attenuated vaccines against Salmonella enteritidis: cell-mediated immune response

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    Sandra Torriani

    2010-01-01

    Full Text Available The use of Salmonella enteritidis (SE live attenuated vaccines is one of the major tool to reduce this infection in commercial poultry. In this work, techniques, evaluating the presence and the expression of some cytokines, were studied to improve the knowledge of the cellular-mediated immune response following SE vaccination. This study demonstrated that SE vaccination enhances the production of INF-γ, IL-8, iNOs, while downregulates IL-1β. Between these immunologic parameters, the evaluation of INF-γ seems to be the most significant and easy test to plan and optimize SE vaccination programs.

  7. Post-marketing surveillance of live-attenuated Japanese encephalitis vaccine safety in China.

    Science.gov (United States)

    Wang, Yali; Dong, Duo; Cheng, Gang; Zuo, Shuyan; Liu, Dawei; Du, Xiaoxi

    2014-10-07

    Japanese encephalitis (JE) is the most severe form of viral encephalitis in Asia and no specific treatment is available. Vaccination provides an effective intervention to prevent JE. In this paper, surveillance data for adverse events following immunization (AEFI) related to SA-14-14-2 live-attenuated Japanese encephalitis vaccine (Chengdu Institute of Biological Products) was presented. This information has been routinely generated by the Chinese national surveillance system for the period 2009-2012. There were 6024 AEFI cases (estimated reported rate 96.55 per million doses). Most common symptoms of adverse events were fever, redness, induration and skin rash. There were 70 serious AEFI cases (1.12 per million doses), including 9 cases of meningoencephalitis and 4 cases of death. The post-marketing surveillance data add the evidence that the Chengdu institute live attenutated vaccine has a reasonable safety profile. The relationship between encephalitis and SA-14-14-2 vaccination should be further studied.

  8. Live Attenuated Human Salmonella Vaccine Candidates: Tracking the Pathogen in Natural Infection and Stimulation of Host Immunity.

    Science.gov (United States)

    Galen, James E; Buskirk, Amanda D; Tennant, Sharon M; Pasetti, Marcela F

    2016-11-01

    Salmonellosis, caused by members of the genus Salmonella, is responsible for considerable global morbidity and mortality in both animals and humans. In this review, we will discuss the pathogenesis of Salmonella enterica serovar Typhi and Salmonella enterica serovar Typhimurium, focusing on human Salmonella infections. We will trace the path of Salmonella through the body, including host entry sites, tissues and organs affected, and mechanisms involved in both pathogenesis and stimulation of host immunity. Careful consideration of the natural progression of disease provides an important context in which attenuated live oral vaccines can be rationally designed and developed. With this in mind, we will describe a series of attenuated live oral vaccines that have been successfully tested in clinical trials and demonstrated to be both safe and highly immunogenic. The attenuation strategies summarized in this review offer important insights into further development of attenuated vaccines against other Salmonella for which live oral candidates are currently unavailable.

  9. Live Attenuated Human Salmonella Vaccine Candidates: tracking the pathogen in natural infection and stimulation of host immunity

    Science.gov (United States)

    Galen, James E.; Buskirk, Amanda D.; Tennant, Sharon M.; Pasetti, Marcela F.

    2016-01-01

    Salmonellosis, caused by members of the genus Salmonella, is responsible for considerable global morbidity and mortality, in both animals and humans. In this review, we will discuss the pathogenesis of S. Typhi and S. Typhimurium, focusing on human Salmonella infections. We will trace the path of Salmonella through the body, including host entry sites, tissues and organs affected, and mechanisms involved in both pathogenesis and stimulation of host immunity. Careful consideration of the natural progression of disease provides an important context in which attenuated live oral vaccines can be rationally designed and developed. With this in mind, we will describe a series of attenuated live oral vaccines that have been successfully tested in clinical trials and demonstrated to be both safe and highly immunogenic. The attenuation strategies summarized in this review offer important insights into further development of attenuated vaccines against other Salmonella for which live oral candidates are currently unavailable. PMID:27809955

  10. Cross-protection against Salmonella Typhimurium infection conferred by a live attenuated Salmonella Enteritidis vaccine.

    Science.gov (United States)

    Nandre, Rahul M; Lee, Dajeong; Lee, John Hwa

    2015-01-01

    In this study, a genetically engineered live attenuated Salmonella Enteritidis (SE) vaccine was evaluated for its ability to protect against Salmonella Typhimurium (ST) infection in chickens. The birds were orally primed with the vaccine on the 1st day of life and given an oral booster at 5 wk of age. Control birds were orally inoculated with phosphate-buffered saline. Both groups of birds were orally challenged with a virulent ST strain at 9 wk of age. Compared with the control chickens, the vaccinated chickens had significantly higher levels of systemic IgG and mucosal IgA against specific ST antigens and a significantly greater lymphoproliferative response to ST antigens. The excretion of ST into the feces was significantly lower in the vaccinated group than in the control group on days 9 and 13 d after challenge. In addition, the vaccinated group had significantly fewer pronounced gross lesions in the liver and spleen and lower bacterial counts in the internal organs than the control group after challenge. These data indicate that genetically engineered live attenuated SE may induce humoral and cellular immune responses against ST antigens and may confer protection against virulent ST challenge.

  11. Live attenuated HIV vaccines: predicting the tradeoff between efficacy and safety.

    Science.gov (United States)

    Blower, S M; Koelle, K; Kirschner, D E; Mills, J

    2001-03-13

    The utility of live attenuated vaccines for controlling HIV epidemics is being debated. Live attenuated HIV vaccines (LAHVs) could be extremely effective in protecting against infection with wild-type strains, but may not be completely safe as the attenuated strain could cause AIDS in some vaccinated individuals. We present a theoretical framework for evaluating the consequences of the tradeoff between vaccine efficacy (in terms of preventing new infections with wild-type strains) and safety (in terms of vaccine-induced AIDS deaths). We use our framework to predict, for Zimbabwe and Thailand, the epidemiological impact of 1,000 different (specified by efficacy and safety characteristics) LAHVs. We predict that paradoxically: (i) in Zimbabwe (where transmission is high) LAHVs would significantly decrease the AIDS death rate, but (ii) in Thailand (where transmission is low) exactly the same vaccines (in terms of efficacy and safety characteristics) would increase the AIDS death rate. Our results imply that a threshold transmission rate exists that determines whether any given LAHV has a beneficial or a detrimental impact. We also determine the vaccine perversity point, which is defined in terms of the fraction of vaccinated individuals who progress to AIDS as a result of the vaccine strain. Vaccination with any LAHV that causes more than 5% of vaccinated individuals to progress to AIDS in 25 years would, even 50 years later, lead to perversity (i.e., increase the annual AIDS death rate) in Thailand; these same vaccines would lead to decreases in the annual AIDS death rate in Zimbabwe.

  12. A live attenuated strain of Yersinia pestis KIM as a vaccine against plague.

    Science.gov (United States)

    Sun, Wei; Six, David; Kuang, Xiaoying; Roland, Kenneth L; Raetz, Christian R H; Curtiss, Roy

    2011-04-01

    Yersinia pestis, the causative agent of plague, is a potential weapon of bioterrorism. Y. pestis evades the innate immune system by synthesizing tetra-acylated lipid A with poor Toll-like receptor 4 (TLR4)-stimulating activity at 37°C, whereas hexa-acylated lipid A, a potent TLR4 agonist, is made at lower temperatures. Synthesis of Escherichia coli LpxL, which transfers the secondary laurate chain to the 2'-position of lipid A, in Y. pestis results in production of hexa-acylated lipid A at 37°C, leading to significant attenuation of virulence. Previously, we described a Y. pestis vaccine strain in which crp expression is under the control of the arabinose-regulated araC P(BAD) promoter, resulting in a 4-5 log reduction in virulence. To reduce the virulence of the crp promoter mutant further, we introduced E. coli lpxL into the Y. pestis chromosome. The χ10030(pCD1Ap) (ΔlpxP32::P(lpxL)lpxL ΔP(crp21)::TT araC P(BAD)crp) construct likewise produced hexa-acylated lipid A at 37°C and was significantly more attenuated than strains harboring each individual mutation. The LD(50) of the mutant in mice, when administered subcutaneously or intranasally was >10(7)-times and >10(4)-times greater than wild type, respectively. Mice immunized subcutaneously with a single dose of the mutant were completely protected against a subcutaneous challenge of 3.6×10(7) wild-type Y. pestis and significantly protected (80% survival) against a pulmonary challenge of 1.2×10(4) live cells. Intranasal immunization also provided significant protection against challenges by both routes. This mutant is an immunogenic, highly attenuated live Y. pestis construct that merits further development as a vaccine candidate.

  13. [Multifocal epileptic crises following mumps].

    Science.gov (United States)

    Parain, D; Boulloche, J

    1988-04-01

    A 15 years-old girl with no previous history of epilepsy or neurological disease presented three types of epileptic symptoms the same day: 1) clusters of rhythmic myoclonus of the left hemiface; 2) episodes of painful paresthesias of the left arm followed by secondary generalised seizures; 3) episodes of elementary visual hallucinations of the right hemifield. She had several seizures each hour and some were recorded. There were no EEG abnormalities during the facial myoclonus but rapid rhythms were seen during the sensory and visual partial seizures on the right parietal and left occipital lobes. There was no fever and no drowsiness. The CSF tap showed pleocytosis. Serological studies indicated recent mumps. The drugs were initially inefficient. The seizures disappeared after a month. The drugs were stopped after three months and the seizures had not relapsed after a one year's follow-up. Though there were no other sign of encephalitis, we believe that episode of multifocal seizures was due to mumps encephalitis.

  14. Characterization of immune responses induced by inactivated, live attenuated and DNA vaccines against Japanese encephalitis virus in mice.

    Science.gov (United States)

    Li, Jieqiong; Chen, Hui; Wu, Na; Fan, Dongying; Liang, Guodong; Gao, Na; An, Jing

    2013-08-28

    Vaccination is the most effective countermeasure for protecting individuals from Japanese encephalitis virus (JEV) infection. There are two types of JEV vaccines currently used in China: the Vero cell-derived inactivated vaccine and the live attenuated vaccine. In this study, we characterized the immune response and protective efficacy induced in mice by the inactivated vaccine, live attenuated vaccine and the DNA vaccine candidate pCAG-JME, which expresses JEV prM-E proteins. We found that the live attenuated vaccine conferred 100% protection and resulted in the generation of high levels of specific anti-JEV antibodies and cytokines. The pCAG-JME vaccine induced protective immunity as well as the live attenuated vaccine. Unexpectedly, immunization with the inactivated vaccine only induced a limited immune response and partial protection, which may be due to the decreased activity of dendritic cells and the expansion of CD4+CD25+Foxp3+ regulatory T cells observed in these mice. Altogether, our results suggest that the live attenuated vaccine is more effective in providing protection against JEV infection than the inactivated vaccine and that pCAG-JME will be a potential JEV vaccine candidate. Copyright © 2013 Elsevier Ltd. All rights reserved.

  15. Immunogenicity and safety of a two-dose regimen of a combined measles, mumps, rubella and varicella live vaccine (ProQuad(®)) in infants from 9 months of age.

    Science.gov (United States)

    Vesikari, Timo; Becker, Thomas; Gajdos, Vincent; Fiquet, Anne; Thomas, Stéphane; Richard, Patrick; Baudin, Martine

    2012-04-26

    Vaccination against measles, mumps, rubella and varicella (MMRV) is currently recommended in developed countries for infants from 12 months of age. However, measles vaccination at 9 months of age is recommended by the WHO in the Expanded Program on Immunization (EPI) schedule and it is therefore possible that MMR or MMRV vaccines might also be given at this age. This open-label, randomised, comparative study evaluated the immunogenicity and safety of a 2-dose schedule of ProQuad(®) (MMRV vaccine) given at a 3-month interval in healthy infants aged ≥9 months. For measles, the non-inferiority of the response rate post-Dose 2 was reached when Dose 1 was administered at 11 months (98%) compared with 12 months (99%) but was not reached when Dose 1 was administered at 9 months (95%). The response rate to measles post-Dose 1 increased with age, from 73% to 88% and 90% at 9, 11 and 12 months, respectively. For mumps, rubella and varicella, response rates were not different after Dose 1 (>95%) or Dose 2 (>99%) regardless of whether Dose 1 was administered at 9, 11 or 12 months of age. In conclusion, the age of administration of the first of a two-dose regimen of ProQuad may be lowered to 11 months. Dose 1 may be administered at 9 months if early protection is required, but it should be recognised that a second dose is required promptly with a minimum of 3-month interval between doses.

  16. MMR Vaccine (Measles, Mumps, and Rubella)

    Science.gov (United States)

    Attenuvax® Measles Vaccine ... R-Vax® II (as a combination product containing Measles Vaccine, Rubella Vaccine) ... M-R® II (as a combination product containing Measles Vaccine, Mumps Vaccine, Rubella Vaccine)

  17. NNDSS - Table II. Mumps to Rabies, animal

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Mumps to Rabies, animal - 2015.In this Table, provisional cases of selected notifiable diseases (≥1,000 cases reported during the preceding...

  18. NNDSS - Table II. Mumps to Rabies, animal

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Mumps to Rabies, animal - 2014.In this Table, all conditions with a 5-year average annual national total of more than or equals 1,000 cases but...

  19. Increasing uptake of live attenuated influenza vaccine among children in the United States, 2008-2014.

    Science.gov (United States)

    Rodgers, Loren; Pabst, Laura J; Chaves, Sandra S

    2015-01-01

    The Advisory Committee on Immunization Practices (ACIP) recommends annual influenza vaccination for all persons in the United States aged ≥6 months. On June 25, 2014, ACIP preferentially recommended live attenuated influenza vaccine (LAIV) for healthy children aged 2-8 years. Little is known about national LAIV uptake. To determine uptake of LAIV relative to inactivated influenza vaccine, we analyzed vaccination records from six immunization information system sentinel sites (approximately 10% of US population). LAIV usage increased over time in all sites. Among children 2-8 years of age vaccinated for influenza, exclusive LAIV usage in the collective sentinel site area increased from 20.1% (2008-09 season) to 38.0% (2013-14). During 2013-14, at least half of vaccinated children received LAIV in Minnesota (50.0%) and North Dakota (55.5%). Increasing LAIV usage suggests formulation acceptability, and this preexisting trend offers a favorable context for implementation of ACIP's preferential recommendation.

  20. The yellow fever 17D virus as a platform for new live attenuated vaccines.

    Science.gov (United States)

    Bonaldo, Myrna C; Sequeira, Patrícia C; Galler, Ricardo

    2014-01-01

    The live-attenuated yellow fever 17D virus is one of the most outstanding human vaccines ever developed. It induces efficacious immune responses at a low production cost with a well-established manufacture process. These advantages make the YF17D virus attractive as a vector for the development of new vaccines. At the beginning of vector development studies, YF17D was genetically manipulated to express other flavivirus prM and E proteins, components of the viral envelope. While these 17D recombinants are based on the substitution of equivalent YF17D genes, other antigens from unrelated pathogens have also been successfully expressed and delivered by recombinant YF17D viruses employing alternative strategies for genetic manipulation of the YF17D genome. Herein, we discuss these strategies in terms of possibilities of single epitope or larger sequence expression and the main properties of these replication-competent viral platforms.

  1. African horse sickness in The Gambia: circulation of a live-attenuated vaccine-derived strain.

    Science.gov (United States)

    Oura, C A L; Ivens, P A S; Bachanek-Bankowska, K; Bin-Tarif, A; Jallow, D B; Sailleau, C; Maan, S; Mertens, P C; Batten, C A

    2012-03-01

    African horse sickness virus serotype 9 (AHSV-9) has been known for some time to be circulating amongst equids in West Africa without causing any clinical disease in indigenous horse populations. Whether this is due to local breeds of horses being resistant to disease or whether the AHSV-9 strains circulating are avirulent is currently unknown. This study shows that the majority (96%) of horses and donkeys sampled across The Gambia were seropositive for AHS, despite most being unvaccinated and having no previous history of showing clinical signs of AHS. Most young horses (horses. Sequence analysis revealed the presence of an AHSV-9 strain showing 100% identity to Seg-2 of the AHSV-9 reference strain, indicating that the virus circulating in The Gambia was highly likely to have been derived from a live-attenuated AHSV-9 vaccine strain.

  2. Attenuated total reflection Fourier-transform infrared (ATR-FTIR) imaging of tissues and live cells.

    Science.gov (United States)

    Andrew Chan, K L; Kazarian, Sergei G

    2016-04-07

    FTIR spectroscopic imaging is a label-free, non-destructive and chemically specific technique that can be utilised to study a wide range of biomedical applications such as imaging of biopsy tissues, fixed cells and live cells, including cancer cells. In particular, the use of FTIR imaging in attenuated total reflection (ATR) mode has attracted much attention because of the small, but well controlled, depth of penetration and corresponding path length of infrared light into the sample. This has enabled the study of samples containing large amounts of water, as well as achieving an increased spatial resolution provided by the high refractive index of the micro-ATR element. This review is focused on discussing the recent developments in FTIR spectroscopic imaging, particularly in ATR sampling mode, and its applications in the biomedical science field as well as discussing the future opportunities possible as the imaging technology continues to advance.

  3. Is a booster dose necessary in children after immunization with live attenuated Japanese encephalitis vaccine?

    Science.gov (United States)

    Choi, Ui Yoon; Lee, Soo Young; Kim, Ki Hwan; Kim, Dong Soo; Choi, Kyong Min; Cha, Sung Ho; Kang, Jin Han

    2013-10-01

    Japanese encephalitis virus is a common cause of encephalitis in Asian children; therefore, maintenance of immunity against Japanese encephalitis virus is essential. Although many countries recommend booster vaccination, some trials have concluded that administration of one or two vaccinations is sufficient. The current study was conducted to evaluate immunogenicity and safety after a booster vaccination with live attenuated vaccine. For 68 study subjects, measurement of antibody titer was performed before and at 4-6 weeks after administration of a booster dose. Adverse reactions occurring at the injection site and systemic adverse reactions were documented. The percentages of subjects with seroprotective neutralizing antibody titers was 100% before and after booster vaccination, and the geometric mean titer increased after booster vaccination. Thus, we predict that immunity will be maintained for a long time by an amnestic response. Low percentages of adverse reactions indicated the safety of the immunizations.

  4. Safety and immunogenicity of a live attenuated Japanese encephalitis chimeric virus vaccine (IMOJEV®) in children.

    Science.gov (United States)

    Chokephaibulkit, K; Houillon, G; Feroldi, E; Bouckenooghe, A

    2016-01-01

    JE-CV (IMOJEV®, Sanofi Pasteur, France) is a live attenuated virus vaccine constructed by inserting coding sequences of the prM and E structural proteins of the Japanese encephalitis SA14-14-2 virus into the genome of yellow fever 17D virus. Primary immunization with JE-CV requires a single dose of the vaccine. This article reviews clinical trials of JE-CV in children aged up to 6 years conducted in countries across South-East Asia. Strong and persistent antibody responses were observed after single primary and booster doses, with 97% of children seroprotected up to five years after booster vaccination. Models of long-term antibody persistence predict a median duration of protection of approximately 30 years after a booster dose. The safety and reactogenicity profiles of JE-CV primary and booster doses are comparable to other widely used childhood vaccines.

  5. Self-immunization with live attenuated influenza vaccine in a mass vaccination clinic.

    Science.gov (United States)

    Zahn, Matt; Pursiful, Priscilla; Carrico, Ruth; Woods, Charles; Troutman, Adewale

    2013-04-01

    An influenza pandemic may demand that a large number of influenza immunizations be rapidly given with limited resources. This study tested the utility and practicality of self-immunization with live attenuated influenza intranasal vaccine in a mass vaccination event. The self-immunization clinic model was evaluated in a three-tiered fashion using student, first responder, and open community events. A single nurse was easily able to direct 89 people through the process of self-administration of the vaccine in a three-hour first-responder event and 122 people in a three-hour open community event. 96% of participants believed that they had performed the self-administration correctly, and the same percentage reported that they would like to receive influenza immunization by self-vaccination in the future. The self-immunization clinic is a practical and potentially useful model in an influenza pandemic setting.

  6. Live attenuated B. pertussis as a single-dose nasal vaccine against whooping cough.

    Directory of Open Access Journals (Sweden)

    Nathalie Mielcarek

    2006-07-01

    Full Text Available Pertussis is still among the principal causes of death worldwide, and its incidence is increasing even in countries with high vaccine coverage. Although all age groups are susceptible, it is most severe in infants too young to be protected by currently available vaccines. To induce strong protective immunity in neonates, we have developed BPZE1, a live attenuated Bordetella pertussis strain to be given as a single-dose nasal vaccine in early life. BPZE1 was developed by the genetic inactivation or removal of three major toxins. In mice, BPZE1 was highly attenuated, yet able to colonize the respiratory tract and to induce strong protective immunity after a single nasal administration. Protection against B. pertussis was comparable to that induced by two injections of acellular vaccine (aPV in adult mice, but was significantly better than two administrations of aPV in infant mice. Moreover, BPZE1 protected against Bordetella parapertussis infection, whereas aPV did not. BPZE1 is thus an attractive vaccine candidate to protect against whooping cough by nasal, needle-free administration early in life, possibly at birth.

  7. Quantitative polymerase chain reaction: another tool to evaluate viable virus content in live attenuated orf vaccine

    Directory of Open Access Journals (Sweden)

    Durlav Prasad Bora

    2012-12-01

    Full Text Available A probe-based real-time polymerase chain reaction (PCR assay based on the highly conserved DNA polymerase gene of orf virus (ORFV for the quality control of attenuated orf vaccine is reported. Primary lamb testis (PLT cells were infected with orf vaccine virus and harvested at a critical time point to obtain maximum viable virus content as determined by real-time PCR. DNA extracted from these harvests was subjected to real-time PCR. A critical time point for the harvesting of PLT cells infected with various log10 dilutions of vaccine virus was found to be 42 h (highest slope of 3.335, which was obtained by comparing the slopes of standard curves of different time intervals. The assay was employed to evaluate viable virus content in different batches of orf vaccine. The titres estimated by real-time PCR and conventional TCID50 were comparable with a correlation of 0.8169. Thus, the real-time PCR assay could provide an alternative method or supplementary tool to estimate live ORFV particles in attenuated orf vaccine.

  8. Efficacy of a live attenuated vaccine in classical swine fever virus postnatally persistently infected pigs.

    Science.gov (United States)

    Muñoz-González, Sara; Perez-Simó, Marta; Muñoz, Marta; Bohorquez, José Alejandro; Rosell, Rosa; Summerfield, Artur; Domingo, Mariano; Ruggli, Nicolas; Ganges, Llilianne

    2015-07-09

    Classical swine fever (CSF) causes major losses in pig farming, with various degrees of disease severity. Efficient live attenuated vaccines against classical swine fever virus (CSFV) are used routinely in endemic countries. However, despite intensive vaccination programs in these areas for more than 20 years, CSF has not been eradicated. Molecular epidemiology studies in these regions suggests that the virus circulating in the field has evolved under the positive selection pressure exerted by the immune response to the vaccine, leading to new attenuated viral variants. Recent work by our group demonstrated that a high proportion of persistently infected piglets can be generated by early postnatal infection with low and moderately virulent CSFV strains. Here, we studied the immune response to a hog cholera lapinised virus vaccine (HCLV), C-strain, in six-week-old persistently infected pigs following post-natal infection. CSFV-negative pigs were vaccinated as controls. The humoral and interferon gamma responses as well as the CSFV RNA loads were monitored for 21 days post-vaccination. No vaccine viral RNA was detected in the serum samples and tonsils from CSFV postnatally persistently infected pigs for 21 days post-vaccination. Furthermore, no E2-specific antibody response or neutralising antibody titres were shown in CSFV persistently infected vaccinated animals. Likewise, no of IFN-gamma producing cell response against CSFV or PHA was observed. To our knowledge, this is the first report demonstrating the absence of a response to vaccination in CSFV persistently infected pigs.

  9. Persistent efficacy of live attenuated hepatitis A vaccine (H2-strain) after a mass vaccination program

    Institute of Scientific and Technical Information of China (English)

    ZHUANG Fang-cheng; QIAN Wen; MAO Zi-an; GONG Yue-ping; JIANG Qi; JIANG Li-min; CHEN Nian-liang; CHAI Shao-ai; MAO Jiang-sen

    2005-01-01

    Background Live attenuated hepatitis A vaccine (H2 strain) is widely applied in prevention of hepatitis A epidemic in China and other countries now. It is essential to observe and confirm the vaccine immune efficacy, population antibody level and its persistent efficacy after mass immunization.Methods A total of 220 children with negative anti-HAV antibody (aged 1-3 years) were taken for follow-up assay to observe seroconversion and geometric mean titre(GMT)level 2 months, 12 months, 6 years, and 10 years after inoculation. Another survey sampled from subjects of different age groups (3, 6, 9, 15, 18, 25 and 35 years) to compare anti-HA antibody positive rate before and after inoculation performed 10 years previously. Epidemiological observations were taken for 10 years to evaluate the relationship between vaccine coverage and hepatitis A morbidity. Serum antibody to HAV was detected by enzyme linked immunoassay (ELISA, calibrated by WHO international reference) and ABBOTT Axsym HAVAB microparticle enzyme immunoassay. Results Seroconversion in follow-up assay 2 months and 10 years after inoculation was 98.6% and 80.2% respectively. For children, the vaccination anti-HA antibody positive rates were significantly different before and after 10 years, 7.69% cf 70.45% (aged 3 years) and 52.58% cf 71.78% (aged 18 years). When vaccine coverage rose from 57% to 74%, there were no any HA epidemics. When vaccine coverage reached 85%, there were no any HA cases. With vaccine coverage between 85% and 91%, there were no any HA cases in cohorts from the age of 1 year to 15 years during the 10 years. Conclusions Live attenuated hepatitis A vaccine has an obvious long-term effectiveness in prevention and control of HA epidemics through mass vaccination.

  10. Superior protection elicited by live-attenuated vaccines in the murine model of paratuberculosis.

    Science.gov (United States)

    Ghosh, Pallab; Shippy, Daniel C; Talaat, Adel M

    2015-12-16

    Mycobacterium avium subspecies paratuberculosis (M. paratuberculosis) causes Johne's disease, a chronic enteric infection in ruminants with severe economic impact on the dairy industry in the USA and worldwide. Currently, available vaccines have limited protective efficacy against disease progression and does not prevent spread of the infection among animals. Because of their ability to elicit wide-spectrum immune responses, we adopted a live-attenuated vaccine approach based on a sigH knock-out strain of M. paratuberculosis (ΔsigH). Earlier analysis of the ΔsigH mutant in mice indicated their inadequate ability to colonize host tissues, unlike the isogenic wild-type strain, validating the role of this sigma factor in M. paratuberculosis virulence. In the present study, we evaluated the performance of the ΔsigH mutant compared to inactivated vaccine constructs in a vaccine/challenge model of murine paratuberculosis. The presented analysis indicated that ΔsigH mutant with or without QuilA adjuvant is capable of eliciting strong immune responses (such as interferon gamma-γ, IFN-γ) suggesting their immunogenicity and ability to potentially initiate effective vaccine-induced immunity. Following a challenge with virulent strains of M. paratuberculosis, ΔsigH conferred protective immunity as indicated by the reduced bacterial burden accompanied with reduced lesions in main body organs (liver, spleen and intestine) usually infected with M. paratuberculosis. More importantly, our data indicated better ability of the ΔsigH vaccine to confer protection compared to the inactivated vaccine constructs even with the presence of oil-adjuvant. Overall, our approach provides a rational basis for using live-attenuated mutant strains to develop improved vaccines that elicit robust immunity against this chronic infection.

  11. Mumps

    Science.gov (United States)

    ... fever could be an indication of inflamed tonsils (tonsillitis) or a blocked salivary gland. Other viruses can ... and symptoms? Are there other possible causes? What treatment approach do you recommend? How soon should symptoms ...

  12. Mumps

    Science.gov (United States)

    ... and the brain. It can also lead to hearing loss and meningitis (infection of membranes that cover the ... ice or heat packs on swollen cheeks.Take acetaminophen (brand name: Tylenol) for pain or ibuprofen (brand ...

  13. Mumps and the Vaccine (Shot) to Prevent It

    Science.gov (United States)

    ... Immunizations Mumps and the Vaccine (Shot) to Prevent It Language: English Español (Spanish) Format: Select one PDF [ ... sick but will not have swollen glands. Is it serious? In most children, mumps is pretty mild. ...

  14. A live attenuated vaccine prevents replication and transmission of H7N9 virus in mammals

    Science.gov (United States)

    Kong, Huihui; Zhang, Qianyi; Gu, Chunyang; Shi, Jianzhong; Deng, Guohua; Ma, Shujie; Liu, Jinxiong; Chen, Pucheng; Guan, Yuntao; Jiang, Yongping; Chen, Hualan

    2015-01-01

    The continued spread of the newly emerged H7N9 viruses among poultry in China, together with the emergence of drug-resistant variants and the possibility of human-to-human transmission, has spurred attempts to develop an effective vaccine. An MF59-adjuvant H7N9 inactivated vaccine is reported to be well-tolerated and immunogenic in humans; however a study in ferrets indicated that while a single dose of the inactivated H7N9 vaccine reduced disease severity, it did not prevent virus replication and transmission. In this study, we used reverse genetics to produce a cold-adapted, live attenuated H7N9 vaccine (H7N9/AAca) that contains wild-type HA and NA genes from AH/1, and the backbone of the cold-adapted influenza H2N2 A/Ann Arbor/6/60 virus (AAca). H7N9/AAca was attenuated in mice and ferrets, and induced robust neutralizing antibody responses in rhesus mice, ferrets, and guinea pigs immunized once or twice intranasally. The animals immunized twice were completely protected from H7N9 virus challenge. Importantly, the animals vaccinated once were fully protected from transmission when exposed to or in contact with the H7N9 virus-inoculated animals. These results demonstrate that a cold-adapted H7N9 vaccine can prevent H7N9 virus transmission; they provide a compelling argument for further testing of this vaccine in human trials. PMID:26058711

  15. Production and efficacy of an attenuated live vaccine against contagious ovine ecthyma

    Directory of Open Access Journals (Sweden)

    Attilio Pini

    2008-09-01

    Full Text Available Contagious ecthyma is caused by the orf virus, a member of the family Poxviridae, genus Parapoxvirus. Morbidity in affected sheep flocks is approximately 100%, while mortality varies between 1% and 10%. A live attenuated vaccine was produced by the Istituto Zooprofilattico Sperimentale dell’Abruzzo e del Molise ‘G. Caporale’. Quality control was performed in accordance with the European Pharmacopoeia. A wild virus strain was attenuated through serial passages on primary chicken embryo fibroblast tissue cultures. The virus suspension was treated according to standard procedures and freeze dried. The immunising dose was 1 ml containing 104,5TCID50, administered intramuscularly. The safety of the vaccine was successfully tested by intramuscular inoculation of 20 susceptible sheep and 20 lambs with the routine dose, 10 times the immunising dose and two normal doses administered at seven-day intervals. The efficacy of the vaccine was tested using three groups of susceptible animals. The first group included 10 lambs and the second 10 adult sheep; the animals were immunised intramuscularly with 1 ml of the reconstituted vaccine. The third group, used as controls, included five sheep and five lambs. Serological reactivity was monitored by indirect enzyme-linked immunosorbent assay (ELISA. The animals were challenged 30 days later with a pathogenic strain administered intradermally along the labial area. Vaccinated animals did not show any clinical signs of disease, whereas all the controls developed typical signs of contagious ecthyma. To confirm the efficacy of the vaccine, a field trial was conducted in four flocks affected by the disease. The trial showed that the vaccine was able to block the normal course of the disease and induce rapid recovery.

  16. Rapid strategy for screening by pyrosequencing of influenza virus reassortants--candidates for live attenuated vaccines.

    Directory of Open Access Journals (Sweden)

    Svetlana V Shcherbik

    Full Text Available BACKGROUND: Live attenuated influenza vaccine viruses (LAIVs can be generated by classical reassortment of gene segments between a cold adapted, temperature sensitive and attenuated Master Donor Virus (MDV and a seasonal wild-type (wt virus. The vaccine candidates contain hemagglutinin (HA and neuraminidase (NA genes derived from the circulating wt viruses and the remaining six genes derived from the MDV strains. Rapid, efficient selection of the viruses with 6∶2 genome compositions from the large number of genetically different viruses generated during reassortment is essential for the biannual production schedule of vaccine viruses. METHODOLOGY/PRINCIPAL FINDINGS: This manuscript describes a new approach for the genotypic analysis of LAIV reassortant virus clones based on pyrosequencing. LAIV candidate viruses were created by classical reassortment of seasonal influenza A (H3N2 (A/Victoria/361/2011, A/Ohio/02/2012, A/Texas/50/2012 or influenza A (H7N9 (A/Anhui/1/2013 wt viruses with the MDV A/Leningrad/134/17/57(H2N2. Using strain-specific pyrosequencing assays, mixed gene variations were detected in the allantoic progenies during the cloning procedure. The pyrosequencing analysis also allowed for estimation of the relative abundance of segment variants in mixed populations. This semi-quantitative approach was used for selecting specific clones for the subsequent cloning procedures. CONCLUSIONS/SIGNIFICANCE: The present study demonstrates that pyrosequencing analysis is a useful technique for rapid and reliable genotyping of reassortants and intermediate clones during the preparation of LAIV candidates, and can expedite the selection of vaccine virus candidates.

  17. Attempt to develop live attenuated bacterial vaccines by selecting resistance to gossypol, proflavine hemisulfate, novobiocin, or ciprofloxacin

    Science.gov (United States)

    In an attempt to develop attenuated bacteria as potential live vaccines, four chemicals (gossypol, proflavine hemisulfate, novobiocin, and ciprofloxacin) were used to modify the following four genera of bacteria through chemical-resistance strategy: 1) Aeromonas hydrophila (9 isolates); 2) Edwardsie...

  18. Development of live attenuated Streptococcus agalactiae vaccine for tilapia via continuous passage in vitro.

    Science.gov (United States)

    Li, L P; Wang, R; Liang, W W; Huang, T; Huang, Y; Luo, F G; Lei, A Y; Chen, M; Gan, X

    2015-08-01

    Fish Streptococcus agalactiae (S. agalactiae) seriously harms the world's aquaculture industry and causes huge economic losses. This study aimed to develop a potential live attenuated vaccine of S. agalactiae. Pre-screened vaccine candidate strain S. agalactiae HN016 was used as starting material to generate an attenuated strain S. agalactiae YM001 by continuous passage in vitro. The biological characteristics, virulence, and stability of YM001 were detected, and the protective efficacy of YM001 immunization in tilapia was also determined. Our results indicated that the growth, staining, characteristics of pulsed-field gel electrophoresis (PFGE) genotype, and virulence of YM001 were changed significantly as compared to the parental strain HN016. High doses of YM001 by intraperitoneal (IP) injection (1.0 × 10(9) CFU/fish) and oral gavage (1.0 × 10(10) CFU/fish) respectively did not cause any mortality and morbidity in tilapia. The relative percent survivals (RPSs) of fishes immunized with YM001 (1.0 × 10(8) CFU/fish, one time) via injection, immersion, and oral administration were 96.88, 67.22, and 71.81%, respectively, at 15 days, and 93.61, 60.56, and 53.16%, respectively, at 30 days. In all tests with 1-3 times of immunization in tilapia, the dosages at 1 × 10(8) and 1 × 10(9) CFU/fish displayed the similar best results, whereas the immunoprotection of the dosages at 1 × 10(6) and 1 × 10(7) CFU/fish declined significantly (P 0.05). The level of protective antibody elicited by oral immunization was significantly higher compared to that of the control group (P < 0.01), and the antibody reached their maximum levels 14-21 days after the immunization but decreased significantly after 28 days of vaccination. YM001 bacteria were isolated from the brain, liver, kidney, and spleen tissues of fish after oral immunization and the bacteria existed for the longest time in the spleen (up to 15 days). Taken together, this study obtained a safe, stable, and highly

  19. Incidence of mumps and immunity to measles, mumps and rubella among US military recruits, 2000-2004.

    Science.gov (United States)

    Eick, Angelia A; Hu, Zheng; Wang, Zhong; Nevin, Remington L

    2008-01-24

    Recent mumps outbreaks have evoked concerns of decreasing mumps immunity among adolescents and adults, including US military recruits subject to differing mumps immunization policies. To compare mumps incidence and to assess initial measles, mumps and rubella seropositivity, we conducted a cohort study among recruits from 2000 to 2004. Mumps incidence in the targeted MMR and universal MMR cohorts was 4.1 and 3.5 per 100,000 person-years, respectively, giving an incidence rate ratio of 1.16 (P=0.67). Measles, mumps, and rubella seropositivity was 84.6%, 89.5%, and 93.2%, respectively. Among recruits with measles and rubella immunity, 92.8% were mumps immune. These findings support the policy of targeting MMR immunization based upon measles and rubella serology alone.

  20. Mumps: Not an Innocent Bystander in Solid Organ Transplantation

    NARCIS (Netherlands)

    M.C. Baas; K.A.M.I. van Donselaar; S. Florquin; R.S. van Binnendijk; I.J.M. ten Berge; F.J. Bemelman

    2009-01-01

    Recently two major outbreaks of mumps have occurred: in the UK more than 56,000 cases were notified between 2004 and 2005, and in the United States, 6,584 cases were reported in 2006. Most patients were young healthy adults, in whom mumps normally has a benign course. Little is known about mumps in

  1. Biomarkers of safety and immune protection for genetically modified live attenuated Leishmania vaccines against visceral leishmaniasis-Discovery and implications

    Directory of Open Access Journals (Sweden)

    Sreenivas eGannavaram

    2014-05-01

    Full Text Available Despite intense efforts there is no safe and efficacious vaccine against visceral leishmaniasis, which is fatal and endemic in many tropical countries. A major shortcoming in the vaccine development against blood borne parasitic agents such as Leishmania is the inadequate predictive power of the early immune responses mounted in the host against the experimental vaccines. Often immune correlates derived from in-bred animal models do not yield immune markers of protection that can be readily extrapolated to humans. The limited efficacy of vaccines based on DNA, sub-unit, heat killed parasites has led to the realization that acquisition of durable immunity against the protozoan parasites requires a controlled infection with a live attenuated organism. Recent success of irradiated malaria parasites as a vaccine candidate further strengthens this approach to vaccination. We developed several gene deletion mutants in L. donovani as potential live attenuated vaccines and reported extensively on the immunogenicity of LdCentrin1 deleted mutant in mice, hamsters and dogs. Additional limited studies using genetically modified live attenuated Leishmania parasites as vaccine candidates have been reported. However, for the live attenuated parasite vaccines, the primary barrier against widespread use remains the absence of clear biomarkers associated with protection and safety. Recent studies in evaluation of vaccines e.g., influenza and yellow fever vaccines, using systems biology tools demonstrated the power of such strategies in understanding the immunological mechanisms that underpin a protective phenotype. Applying similar tools in isolated human tissues such as PBMCs from healthy individuals infected with live attenuated parasites such as LdCen1-/- in vitro followed by human microarray hybridization experiments will enable us to understand how early vaccine-induced gene expression profiles and the associated immune responses are coordinately regulated

  2. Live attenuated varicella vaccine. Efficacy for children with leukemia in remission.

    Science.gov (United States)

    Gershon, A A; Steinberg, S P; Gelb, L; Galasso, G; Borkowsky, W; LaRussa, P; Farrara, A

    1984-07-20

    One hundred ninety-one varicella-susceptible children with leukemia in remission were immunized with live attenuated varicella vaccine. There was serological evidence of an immune response in approximately 80% after one dose and in more than 90% after two doses. The major side effect was mild to moderate rash, seen especially in children with maintenance chemotherapy suspended for one week before and one week after vaccination. Children with rash had higher antibody titers than those without rash, but those with rash were also at risk (10%) to transmit vaccine virus to others. Twenty-two vaccinees subsequently had household exposures to varicella or zoster. The attack rate of clinical varicella in these vaccinees was 18%, significantly lower than the attack rate of approximately 90% in varicella-susceptible persons with household exposures. All cases of clinical illness were extremely mild, with an average of about 50 vesicles. The mild character of the illness was clearly different than varicella in unimmunized children receiving chemotherapy for leukemia. Varicella vaccine was approximately 80% effective in preventing clinical varicella in children with leukemia and completely effective in preventing severe varicella in this high-risk group.

  3. A multicentre trial of live attenuated varicella vaccine in children with leukaemia in remission.

    Science.gov (United States)

    Gershon, A A; Steinberg, S; Gelb, L; Galasso, G; Borkowsky, W; LaRussa, P; Ferrara, A

    1985-01-01

    Two hundred forty children with acute leukaemia in remission for at least 1 year were immunized with live attenuated varicella vaccine. All were susceptible to varicella before immunization. There was a seroconversion to varicella-zoster virus in approximately 85% after 1 dose, and in 97% after 2 doses. The major side effect was mild to moderate rash, seen mainly in children with maintenance chemotherapy suspended for 1 week before and 1 week after vaccination. Vaccinees with rash were at some risk (10%) to transmit vaccine virus to varicella susceptibles with whom they had close contact. Twenty-nine vaccinees were subsequently exposed to varicella in their households. The attack rate of clinical varicella in these vaccinees was 21%, which is significantly lower than the 80%-90% attack rate occurring in varicella susceptibles after household exposure. All these breakthrough cases of varicella were mild, even in leukaemics receiving chemotherapy. Varicella vaccine was approximately 80% effective in preventing clinical varicella in children with leukaemia and completely effective in preventing severe varicella in this high-risk group.

  4. Antigenic characterization of a formalin-inactivated poliovirus vaccine derived from live-attenuated Sabin strains.

    Science.gov (United States)

    Tano, Yoshio; Shimizu, Hiroyuki; Martin, Javier; Nishimura, Yorihiro; Simizu, Bunsiti; Miyamura, Tatsuo

    2007-10-10

    A candidate inactivated poliovirus vaccine derived from live-attenuated Sabin strains (sIPV), which are used in the oral poliovirus vaccine (OPV), was prepared in a large-production scale. The modification of viral antigenic epitopes during the formalin inactivation process was investigated by capture ELISA assays using type-specific and antigenic site-specific monoclonal antibodies (MoAbs). The major antigenic site 1 was modified during the formalin inactivation of Sabin 1. Antigenic sites 1-3 were slightly modified during the formalin inactivation of Sabin 2 strain. Sites 1 and 3 were altered on inactivated Sabin 3 virus. These alterations were different to those shown by wild-type Saukett strain, used in conventional IPV (cIPV). It has been previously reported that type 1 sIPV showed higher immunogenicity to type 1 cIPV whereas types 2 and 3 sIPV induced lower level of immunogenicity than their cIPV counterparts. Our results suggest that the differences in epitope structure after formalin inactivation may account, at least in part, for the observed differences in immunogenicity between Sabin and wild-type inactivated poliovaccines.

  5. Evaluation of YadC protein delivered by live attenuated Salmonella as a vaccine against plague.

    Science.gov (United States)

    Sun, Wei; Olinzock, Joseph; Wang, Shifeng; Sanapala, Shilpa; Curtiss, Roy

    2014-03-01

    Yersinia pestis YadB and YadC are two new outer membrane proteins related to its pathogenicity. Here, codon-optimized yadC, yadC810 (aa 32-551), or yadBC antigen genes delivered by live attenuated Salmonella strains are evaluated in mice for induction of protective immune responses against Y. pestis CO92 through subcutaneous or intranasal challenge. Our findings indicate that mice immunized with Salmonella synthesizing YadC, YadC810, or YadBC develop significant serum IgG responses to purified recombinant YadC protein. For subcutaneous challenge (approximately 230 LD50 of Y. pestis CO92), mice immunized with Salmonella synthesizing YadC or YadC810 are afforded 50% protection, but no protection by immunization with the Salmonella strain synthesizing YadBC. None of these antigens provided protection against intranasal challenge (approximately 31 LD50 of Y. pestis CO92). In addition, subcutaneous immunization with purified YadC810 protein emulsified with alum adjuvant does not elicit a protective response against Y. pestis administered by either challenge route. © 2013 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

  6. Immunogenicity and safety of a novel formalin-inactivated and alum-adjuvanted candidate subunit vaccine for mumps.

    Science.gov (United States)

    Liang, Yan; Ma, Shaohui; Yang, Zijiang; Liu, Longding; Wang, Lichun; Wang, Jingjing; Jiang, Li; Shi, Changjun; Dong, Chenghong; Li, Qihan

    2008-08-05

    While an attenuated vaccine against mumps has played a role in controlling the epidemic of this disease worldwide, some problems with efficacy and safety of the vaccine are still present. In the work described here, a novel mumps vaccine with good immunity and safety was developed by selecting an antigen component of the mumps virus. The results suggest that this purified antigen vaccine is immunogenic in animals and is capable of inducing a specific neutralizing antibody response against viral HN, but not against other viral proteins. The clinical and pathological observations after challenge of vaccinated rhesus monkeys indicated further that the immune response induced by this vaccine provided complete protection from wild-type virus infection. Furthermore, the immunological analysis and clinical observation of experimental monkeys that were immunized with the vaccine, followed by infection with wild-type virus, suggest that no abnormal changes in expression of inflammatory cytokines and no clinical allergic reaction were found at 1 month after challenge.

  7. HUMAN PAPILLOMAVIRUS TYPE 16 L1 PROTEIN CAN BE EXPRESSED IN LIVE ATTENUATED SHIGELLA FLEXNERI 5A STRAIN SH42

    Institute of Scientific and Technical Information of China (English)

    Qu Xinzhong; Yang Xiaofeng; Zheng Jin; Wang Kai; Si Lüsheng; Wang Yili

    2005-01-01

    Objective Attenuated strains of Shigella are attractive live vaccine candidates for eliciting mucosal immune responses which is a suitable carrier for the prophylactic human papillomaviruses (HPV) vaccine development, To examine the potential of a live Shigella based prophylactic HPV vaccine, HPV16L1should be expressed in attenuated shigella strain. Methods A Shigella large invasive plasmid (icsA/virG) based prokaryotic expression plasmid pHS3199 was constructed. HPV16L1 gene was inserted into plasmid pHS3199 to form pHS3199-HPV16 L1 construct, and pHS3199-hpv16L1 was electroporated into a live attenuated shigella strain sh42. The expression of HPV16L1 protein was demonstrated by Western blotting with monoclonal antibody to HPV16L1, The genetic stability of recombinant strain sh42-HPV16 L1 was monitored by consecutive passage culture. Invasive ability of sh42-HPV16L1 was evaluated by Hela cell infection assay. Results HPV16 L1 protein can be expressed in recombinant strain sh42-HPV16 L1, and the protein stably expressed over 140 generations. The invasive ability of sh42-HPV16L1 was diminished dramatically compared to its parent strain, but not abolished completely. Conclusion HPV16L1 protein was constitutively expressed in the attenuated strain of shigella flexneri sh42, and maintained partial invasive ability. Our strategy may represent a promising vaccine candidate against genital HPV16 infection.

  8. The increasing incidence of mumps orchitis: a comprehensive review.

    Science.gov (United States)

    Davis, Niall F; McGuire, Barry B; Mahon, Jackie A; Smyth, Anna E; O'Malley, Kiaran J; Fitzpatrick, John M

    2010-04-01

    There has been a recent increase in mumps orchitis among pubertal and postpubertal males. These outbreaks can be attributed to a reduction in the uptake of measles-mumps-rubella (MMR) vaccine during the early to mid-1990 s in children who have now matured. The mumps virus is commonly associated with extra-salivary complications. Unvaccinated postpubertal males diagnosed with mumps virus frequently develop complications such as mumps orchitis. Therefore, it is important that urologists are familiar with the diagnosis, treatment and complications of this condition. Here we review the epidemiology, clinical presentation, diagnostic methods, treatment options and complications of mumps orchitis, as a complication of mumps virus, with particular emphasis on testicular atrophy, subfertility and infertility.

  9. DNA vaccine initiates replication of live attenuated chikungunya virus in vitro and elicits protective immune response in mice.

    Science.gov (United States)

    Tretyakova, Irina; Hearn, Jason; Wang, Eryu; Weaver, Scott; Pushko, Peter

    2014-06-15

    Chikungunya virus (CHIKV) causes outbreaks of chikungunya fever worldwide and represents an emerging pandemic threat. Vaccine development against CHIKV has proved challenging. Currently there is no approved vaccine or specific therapy for the disease. To develop novel experimental CHIKV vaccine, we used novel immunization DNA (iDNA) infectious clone technology, which combines the advantages of DNA and live attenuated vaccines. Here we describe an iDNA vaccine composed of plasmid DNA that encode the full-length infectious genome of live attenuated CHIKV clone 181/25 downstream from a eukaryotic promoter. The iDNA approach was designed to initiate replication of live vaccine virus from the plasmid in vitro and in vivo. Experimental CHIKV iDNA vaccines were prepared and evaluated in cultured cells and in mice. Transfection with 10 ng of iDNA was sufficient to initiate replication of vaccine virus in vitro. Vaccination of BALB/c mice with a single 10 μg of CHIKV iDNA plasmid resulted in seroconversion, elicitation of neutralizing antibodies, and protection from experimental challenge with a neurovirulent CHIKV. Live attenuated CHIKV 181/25 vaccine can be delivered in vitro and in vivo by using DNA vaccination. The iDNA approach appears to represent a promising vaccination strategy for CHIK and other alphaviral diseases. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  10. Development of live attenuated Streptococcus agalactiae as potential vaccines by selecting for resistance to sparfloxacin.

    Science.gov (United States)

    Pridgeon, Julia W; Klesius, Phillip H

    2013-05-31

    To develop attenuated bacteria as potential live vaccines, sparfloxacin was used in this study to modify 40 isolates of Streptococcus agalactiae. Majority of S. agalactiae used in this study were able to develop at least 80-fold resistance to sparfloxacin. When the virulence of the sparfloxacin-resistant S. agalactiae isolates were tested in 10-12g Nile tilapia by intraperitoneal injection at dose of 2×10(7)CFU/fish, 31 were found to be avirulent to fish. Of the 31 avirulent sparfloxacin-resistant S. agalactiae isolates, 30 provided 75-100% protection to 10-12g Nile tilapia against challenges with a virulent S. agalactiae isolate Sag 50. When the virulence of the 30 sparfloxacin-resistant S. agalactiae isolates was tested in 3-5g Nile tilapia by intraperitoneal injection at dose of 2×10(7)CFU/fish, six were found to be avirulent to 3-5g Nile tilapia. Of the six avirulent sparfloxacin-resistant S. agalactiae isolates, four provided 3-5g Nile tilapia 100% protection against challenges with homologous isolates, including Sag 97-spar isolate that was non-hemolytic. However, Sag 97-spar failed to provide broad cross-protection against challenges with heterologous isolates. When Nile tilapia was vaccinated with a polyvalent vaccine consisting of 30 sparfloxacin-resistant S. agalactiae isolates at dose of 2×10(6)CFU/fish, the polyvalent vaccine provided significant (P<0.001) protection to both 3-5g and 15-20g Nile tilapia against challenges with 30 parent isolates of S. agalactiae. Taken together, our results suggest that a polyvalent vaccine consisting of various strains of S. agalactiae might be essential to provide broader protection to Nile tilapia against infections caused by S. agalactiae.

  11. CANINE DISTEMPER VIRUS ANTIBODY TITERS IN DOMESTIC CATS AFTER DELIVERY OF A LIVE ATTENUATED VIRUS VACCINE.

    Science.gov (United States)

    Ramsay, Edward; Sadler, Ryan; Rush, Robert; Seimon, Tracie; Tomaszewicz, Ania; Fleetwood, Ellen A; McAloose, Denise; Wilkes, Rebecca P

    2016-06-01

    Three methods for delivering a live attenuated canine distemper virus (CDV) vaccine to domestic cats ( Felis catus ) were investigated, as models for developing vaccination protocols for tigers (Panthera tigris). Twenty domestic cats were randomly divided into four treatment groups: saline injection (negative controls); and oral, intranasal, and subcutaneous vaccinates. Cats were injected with saline or a CDV vaccine (Nobivac DP, Merck) at wk 0 and 4. Blood and nasal swabs were collected at wk 0 (prior to the initial vaccination) and weekly thereafter for 9 wk. Urine samples were collected on wk 1 to 9 after initial vaccination. Forty-nine weeks following the initial vaccination series, three cats from the subcutaneous group and three cats from the intranasal group were revaccinated. Blood was collected immediately prior, and 7 and 21 days subsequent to revaccination. Nasal swabs and urine samples were collected from each cat prior to wk 49 revaccination and daily for 7 days thereafter. Nasal swabs and urine were analyzed by quantitative PCR for vaccine virus presence. Sera were tested for CDV antibodies by virus neutralization. All cats were sero-negative for CDV antibodies at the beginning of the study, and saline-injected cats remained sero-negative throughout the study. A dramatic anamnestic response was seen following wk 4 subcutaneous vaccinations, with titers peaking at wk 6 (geometric mean = 2,435.5). Following wk 49 revaccination, subcutaneous vaccinates again mounted impressive titers (wk 52 geometric mean = 2,048). Revaccination of the intranasal group cats at wk 49 produced a small increase in titers (wk 52 geometric mean = 203). CDV viral RNA was detected in six nasal swabs but no urine samples, demonstrating low viral shedding postvaccination. The strong antibody response to subcutaneous vaccination and the lack of adverse effects suggest this vaccine is safe and potentially protective against CDV infection in domestic cats.

  12. Prophylaxis of tumor through oral administration of IL-12 GM-CSF gene carried by live attenuated salmonella

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    A live attenuated AraA- autotrophic mutant of Salmonella typhimurium (SL3261) was used as carrier for eukaryotic expression vectors EGFPN1, pCMVmIL-12, pCMVhIL-12, pCMVmGM-CSF and pCMVhGM-CSF and was administered orally to BALB/c and C57BL/6 mice. After 6 weeks, these mice were challenged with 4T1 and Lewis tumor cells respectively. GFP expression and gene integrati-on could be detected in mice's livers, spleens, intestines, kidneys and tumors. The serum level of cytokines increased significantly in treated mice, so did the ratio of , which resulted in the tumor regression and prolongation of the survival time of those mice. These researches laid an experimental foundation for the tumor gene therapy using live attenuated salmonella.

  13. Generation of growth arrested Leishmania amastigotes: a tool to develop live attenuated vaccine candidates against visceral leishmaniasis.

    Science.gov (United States)

    Selvapandiyan, Angamuthu; Dey, Ranadhir; Gannavaram, Sreenivas; Solanki, Sumit; Salotra, Poonam; Nakhasi, Hira L

    2014-06-30

    Visceral leishmaniasis (VL) is fatal if not treated and is prevalent widely in the tropical and sub-tropical regions of world. VL is caused by the protozoan parasite Leishmania donovani or Leishmania infantum. Although several second generation vaccines have been licensed to protect dogs against VL, there are no effective vaccines against human VL [1]. Since people cured of leishmaniasis develop lifelong protection, development of live attenuated Leishmania parasites as vaccines, which can have controlled infection, may be a close surrogate to leishmanization. This can be achieved by deletion of genes involved in the regulation of growth and/or virulence of the parasite. Such mutant parasites generally do not revert to virulence in animal models even under conditions of induced immune suppression due to complete deletion of the essential gene(s). In the Leishmania life cycle, the intracellular amastigote form is the virulent form and causes disease in the mammalian hosts. We developed centrin gene deleted L. donovani parasites that displayed attenuated growth only in the amastigote stage and were found safe and efficacious against virulent challenge in the experimental animal models. Thus, targeting genes differentially expressed in the amastigote stage would potentially attenuate only the amastigote stage and hence controlled infectivity may be effective in developing immunity. This review lays out the strategies for attenuation of the growth of the amastigote form of Leishmania for use as live vaccine against leishmaniasis, with a focus on visceral leishmaniasis.

  14. Brainstem Encephalitis and ADEM Following Mumps

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2004-03-01

    Full Text Available Clinical manifestations of brainstem encephalitis (BSE with fever, decreased level of consciousness, and left facial and abducens paralysis developed 1 week after bilateral parotitis and mumps in a 4 year-old female child and were followed by symptoms of acute disseminated encephalomyelitis (ADEM within 20 days of recovery from BSE.

  15. NNDSS - Table II. Mumps to Rabies, animal

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Mumps to Rabies, animal - 2016. In this Table, provisional* cases of selected†notifiable diseases (≥1,000 cases reported during the preceding...

  16. Vaccination with live attenuated simian immunodeficiency virus causes dynamic changes in intestinal CD4+CCR5+ T cells

    Directory of Open Access Journals (Sweden)

    Elsley William

    2011-02-01

    Full Text Available Abstract Background Vaccination with live attenuated SIV can protect against detectable infection with wild-type virus. We have investigated whether target cell depletion contributes to the protection observed. Following vaccination with live attenuated SIV the frequency of intestinal CD4+CCR5+ T cells, an early target of wild-type SIV infection and destruction, was determined at days 3, 7, 10, 21 and 125 post inoculation. Results In naive controls, modest frequencies of intestinal CD4+CCR5+ T cells were predominantly found within the LPL TTrM-1 and IEL TTrM-2 subsets. At day 3, LPL and IEL CD4+CCR5+ TEM cells were dramatically increased whilst less differentiated subsets were greatly reduced, consistent with activation-induced maturation. CCR5 expression remained high at day 7, although there was a shift in subset balance from CD4+CCR5+ TEM to less differentiated TTrM-2 cells. This increase in intestinal CD4+CCR5+ T cells preceded the peak of SIV RNA plasma loads measured at day 10. Greater than 65.9% depletion of intestinal CD4+CCR5+ T cells followed at day 10, but overall CD4+ T cell homeostasis was maintained by increased CD4+CCR5- T cells. At days 21 and 125, high numbers of intestinal CD4+CCR5- naive TN cells were detected concurrent with greatly increased CD4+CCR5+ LPL TTrM-2 and IEL TEM cells at day 125, yet SIV RNA plasma loads remained low. Conclusions This increase in intestinal CD4+CCR5+ T cells, following vaccination with live attenuated SIV, does not correlate with target cell depletion as a mechanism of protection. Instead, increased intestinal CD4+CCR5+ T cells may correlate with or contribute to the protection conferred by vaccination with live attenuated SIV.

  17. Mumps Epidemiology and Mumps Virus Genotypes Circulating in Mainland China during 2013-2015

    Science.gov (United States)

    Cui, Aili; Zhu, Zhen; Hu, Ying; Deng, Xiuying; Sun, Zhaodan; Zhang, Yan; Mao, Naiying; Xu, Songtao; Fang, Xueqiang; Gao, Hui; Si, Yuan; Lei, Yake; Zheng, Huanying; He, Jilan; Wu, Hongwei; Xu, Wenbo

    2017-01-01

    With the implementation of mumps virus (MuV) vaccination in the expanded program on immunization (EPI) in mainland China since 2008, the incidence of mumps has decreased, and the natural epidemic pattern of mumps has slightly changed during 2013–2015. The two epidemic peaks (April-July and November-December) became less obvious than those observed from 2004 to 2012. Children and adolescents younger than 15, particularly in the five-to-nine-year-old age group, remain the target group and should be the focus of high-quality immunization activities in mainland China. However, it was also found that the incidence and reported cases of mumps decreased in each age group during 2013–2015, particularly in the five-to-nine-year-old and ten-to-fourteen-year-old age groups. The proportion of mumps cases among adults in some provinces also increased. Unlike the changes in the epidemiological characteristics of mumps affected by vaccination, the data of MuV virology surveillance indicated that most of the MuV transmission chains have not yet been effectively interrupted, and MuV remains a natural epidemic pattern in mainland China. In the MuV virology surveillance, 194 MuV strains during 2013–2015 were isolated from 10 of 31 provinces in mainland China. Based on the phylogenetic analysis of the small hydrophobic (SH) gene, both genotype F (99.0%) and G (1.0%) were identified, and genotype F was still the predominant genotype continuously circulating in mainland China. Representative genotype F and G strains isolated in China from 1995 to 2012 were selected for further analysis. The results indicated that there were multiple transmission chains within genotype F, with no obvious geographical or time differences. The high genetic diversity of genotype F strains could be a result of the continuous transmission and evolution of the MuV in mainland China. Genotype G was also detected in four provinces in mainland China. Because of the limited epidemiological data, it was

  18. Mumps Epidemiology and Mumps Virus Genotypes Circulating in Mainland China during 2013-2015.

    Science.gov (United States)

    Cui, Aili; Zhu, Zhen; Hu, Ying; Deng, Xiuying; Sun, Zhaodan; Zhang, Yan; Mao, Naiying; Xu, Songtao; Fang, Xueqiang; Gao, Hui; Si, Yuan; Lei, Yake; Zheng, Huanying; He, Jilan; Wu, Hongwei; Xu, Wenbo

    2017-01-01

    With the implementation of mumps virus (MuV) vaccination in the expanded program on immunization (EPI) in mainland China since 2008, the incidence of mumps has decreased, and the natural epidemic pattern of mumps has slightly changed during 2013-2015. The two epidemic peaks (April-July and November-December) became less obvious than those observed from 2004 to 2012. Children and adolescents younger than 15, particularly in the five-to-nine-year-old age group, remain the target group and should be the focus of high-quality immunization activities in mainland China. However, it was also found that the incidence and reported cases of mumps decreased in each age group during 2013-2015, particularly in the five-to-nine-year-old and ten-to-fourteen-year-old age groups. The proportion of mumps cases among adults in some provinces also increased. Unlike the changes in the epidemiological characteristics of mumps affected by vaccination, the data of MuV virology surveillance indicated that most of the MuV transmission chains have not yet been effectively interrupted, and MuV remains a natural epidemic pattern in mainland China. In the MuV virology surveillance, 194 MuV strains during 2013-2015 were isolated from 10 of 31 provinces in mainland China. Based on the phylogenetic analysis of the small hydrophobic (SH) gene, both genotype F (99.0%) and G (1.0%) were identified, and genotype F was still the predominant genotype continuously circulating in mainland China. Representative genotype F and G strains isolated in China from 1995 to 2012 were selected for further analysis. The results indicated that there were multiple transmission chains within genotype F, with no obvious geographical or time differences. The high genetic diversity of genotype F strains could be a result of the continuous transmission and evolution of the MuV in mainland China. Genotype G was also detected in four provinces in mainland China. Because of the limited epidemiological data, it was uncertain

  19. Measles-mumps-rubella vaccination and respiratory syncytial virus-associated hospital contact

    DEFF Research Database (Denmark)

    Benn, Christine Stabell; Sørup, Signe; Stensballe, Lone Graff;

    2015-01-01

    -confirmed RSV hospital contacts at age 14-23 months in all children born in Denmark 1997-2002 who had already received the vaccine against diphtheria, tetanus, pertussis (acellular), polio, and Haemophilus influenzae type b (DTaP-IPV-Hib) at the recommended ages of 3, 5, and 12 months. RESULTS: The study......BACKGROUND: The live measles vaccine has been associated with lower non-measles mortality and admissions in low-income countries. The live measles-mumps-rubella vaccine has also been associated with lower rate of admissions with any type of infection in Danish children; the association...... was strongest for admissions with lower respiratory infections. OBJECTIVE: To examine whether measles, mumps, and rubella (MMR) vaccination was associated with reduced rate of hospital contact related to respiratory syncytial virus (RSV) in a high-income country. METHODS: Nationwide cohort study of laboratory...

  20. MMRV (measles, mumps, rubella, and varicella) vaccine - what you need to know

    Science.gov (United States)

    ... taken in its entirety from the CDC MMRV (Measles, Mumps, Rubell and Varicella) Vaccine Information Statement (VIS): ... Measles, Mumps, Rubella & Varicella Measles, Mumps, Rubella, and Varicella (chickenpox) can be serious diseases: Measles Causes rash, ...

  1. Mutual interference on the immune response to yellow fever vaccine and a combined vaccine against measles, mumps and rubella.

    Science.gov (United States)

    Nascimento Silva, Juliana Romualdo; Camacho, Luiz Antonio B; Siqueira, Marilda M; Freire, Marcos de Silva; Castro, Yvone P; Maia, Maria de Lourdes S; Yamamura, Anna Maya Y; Martins, Reinaldo M; Leal, Maria de Luz F

    2011-08-26

    A randomized trial was conducted to assess the immunogenicity and reactogenicity of yellow fever vaccines (YFV) given either simultaneously in separate injections, or 30 days or more after a combined measles-mumps-rubella (MMR) vaccine. Volunteers were also randomized to YFV produced from 17DD and WHO-17D-213 substrains. The study group comprised 1769 healthy 12-month-old children brought to health care centers in Brasilia for routine vaccination. The reactogenicity was of the type and frequency expected for the vaccines and no severe adverse event was associated to either vaccine. Seroconversion and seropositivity 30 days or more after vaccination against yellow fever was similar across groups defined by YFV substrain. Subjects injected YFV and MMR simultaneously had lower seroconversion rates--90% for rubella, 70% for yellow fever and 61% for mumps--compared with those vaccinated 30 days apart--97% for rubella, 87% for yellow fever and 71% for mumps. Seroconversion rates for measles were higher than 98% in both comparison groups. Geometric mean titers for rubella and for yellow fever were approximately three times higher among those who got the vaccines 30 days apart. For measles and mumps antibodies GMTs were similar across groups. MMR's interference in immune response of YFV and YFV's interference in immune response of rubella and mumps components of MMR had never been reported before but are consistent with previous observations from other live vaccines. These results may affect the recommendations regarding primary vaccination with yellow fever vaccine and MMR.

  2. Nasal lavage natural killer cell function is suppressed in smokers after live attenuated influenza virus

    Directory of Open Access Journals (Sweden)

    Zhou Haibo

    2011-08-01

    Full Text Available Abstract Background Modified function of immune cells in nasal secretions may play a role in the enhanced susceptibility to respiratory viruses that is seen in smokers. Innate immune cells in nasal secretions have largely been characterized by cellular differentials using morphologic criteria alone, which have successfully identified neutrophils as a significant cell population within nasal lavage fluid (NLF cells. However, flow cytometry may be a superior method to fully characterize NLF immune cells. We therefore characterized immune cells in NLF by flow cytometry, determined the effects of live attenuated influenza virus (LAIV on NLF and peripheral blood immune cells, and compared responses in samples obtained from smokers and nonsmokers. Methods In a prospective observational study, we characterized immune cells in NLF of nonsmokers at baseline using flow cytometry and immunohistochemistry. Nonsmokers and smokers were inoculated with LAIV on day 0 and serial nasal lavages were collected on days 1-4 and day 9 post-LAIV. LAIV-induced changes of NLF cells were characterized using flow cytometry. Cell-free NLF was analyzed for immune mediators by bioassay. Peripheral blood natural killer (NK cells from nonsmokers and smokers at baseline were stimulated in vitro with LAIV followed by flow cytometric and mediator analyses. Results CD45(+CD56(-CD16(+ neutrophils and CD45(+CD56(+ NK cells comprised median 4.62% (range 0.33-14.52 and 23.27% (18.29-33.97, respectively, of non-squamous NLF cells in nonsmokers at baseline. LAIV did not induce changes in total NK cell or neutrophil percentages in either nonsmokers or smokers. Following LAIV inoculation, CD16(+ NK cell percentages and granzyme B levels increased in nonsmokers, and these effects were suppressed in smokers. LAIV inoculation enhanced expression of activating receptor NKG2D and chemokine receptor CXCR3 on peripheral blood NK cells from both nonsmokers and smokers in vitro but did not induce

  3. Enhancement of the safety of live influenza vaccine by attenuating mutations from cold-adapted hemagglutinin

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Yoon Jae [Graduate Program in Biomaterials Science and Engineering, College of Life Science and Biotechnology, Yonsei University, Seoul (Korea, Republic of); Laboratory of Molecular Medicine, Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul (Korea, Republic of); Vaccine Translational Research Center, Yonsei University, Seoul (Korea, Republic of); Jang, Yo Han [Laboratory of Molecular Medicine, Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul (Korea, Republic of); Kim, Paul; Lee, Yun Ha; Lee, Young Jae [Laboratory of Molecular Medicine, Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul (Korea, Republic of); Vaccine Translational Research Center, Yonsei University, Seoul (Korea, Republic of); Byun, Young Ho; Lee, Kwang-Hee; Kim, Kyusik [Laboratory of Molecular Medicine, Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul (Korea, Republic of); Seong, Baik Lin, E-mail: blseong@yonsei.ac.kr [Graduate Program in Biomaterials Science and Engineering, College of Life Science and Biotechnology, Yonsei University, Seoul (Korea, Republic of); Laboratory of Molecular Medicine, Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul (Korea, Republic of); Vaccine Translational Research Center, Yonsei University, Seoul (Korea, Republic of)

    2016-04-15

    In our previous study, X-31ca-based H5N1 LAIVs, in particular, became more virulent in mice than the X-31ca MDV, possibly by the introduction of the surface antigens of highly pathogenic H5N1 influenza virus, implying that additional attenuation is needed in this cases to increase the safety level of the vaccine. In this report we suggest an approach to further increase the safety of LAIV through additional cold-adapted mutations in the hemagglutinin. The cold-adaptation of X-31 virus resulted in four amino acid mutations in the HA. We generated a panel of 7:1 reassortant viruses each carrying the hemagglutinins with individual single amino acid mutations. We examined their phenotypes and found a major attenuating mutation, N81K. This attenuation marker conferred additional temperature-sensitive and attenuation phenotype to the LAIV. Our data indicate that the cold-adapted mutation in the HA confers additional attenuation to the LAIV strain, without compromising its productivity and immune response. - Highlights: • Cold-adaptation process induced four amino acid mutations in the HA of X-31 virus. • The four mutations in the HA also contributed to attenuation of the X-31ca virus • N81K mutation was the most significant marker for the attenuation of X-31ca virus. • Introduction of N81K mutation into H3N2 LAIV further attenuated the vaccine. • This approach provides a useful guideline for enhancing the safety of the LAIVs.

  4. Migration of legacy mumps applications to relational database servers.

    Science.gov (United States)

    O'Kane, K C

    2001-07-01

    An extended implementation of the Mumps language is described that facilitates vendor neutral migration of legacy Mumps applications to SQL-based relational database servers. Implemented as a compiler, this system translates Mumps programs to operating system independent, standard C code for subsequent compilation to fully stand-alone, binary executables. Added built-in functions and support modules extend the native hierarchical Mumps database with access to industry standard, networked, relational database management servers (RDBMS) thus freeing Mumps applications from dependence upon vendor specific, proprietary, unstandardized database models. Unlike Mumps systems that have added captive, proprietary RDMBS access, the programs generated by this development environment can be used with any RDBMS system that supports common network access protocols. Additional features include a built-in web server interface and the ability to interoperate directly with programs and functions written in other languages.

  5. Revaccination with Live Attenuated Vaccines Confer Additional Beneficial Nonspecific Effects on Overall Survival: A Review

    Directory of Open Access Journals (Sweden)

    Christine S. Benn

    2016-08-01

    Interpretation: Revaccination with live vaccines led to substantial reductions in overall mortality. These findings challenge current understanding of vaccines and may explain the beneficial effects of campaigns with live vaccines.

  6. Recoding of the vesicular stomatitis virus L gene by computer-aided design provides a live, attenuated vaccine candidate.

    Science.gov (United States)

    Wang, Bingyin; Yang, Chen; Tekes, Gergely; Mueller, Steffen; Paul, Aniko; Whelan, Sean P J; Wimmer, Eckard

    2015-03-31

    Codon pair bias (CPB), which has been observed in all organisms, is a neglected genomic phenomenon that affects gene expression. CPB results from synonymous codons that are paired more or less frequently in ORFeomes regardless of codon bias. The effect of an individual codon pair change is usually small, but when it is amplified by large-scale genome recoding, strikingly altered biological phenotypes are observed. The utility of codon pair bias in the development of live attenuated vaccines was recently demonstrated by recodings of poliovirus (a positive-strand RNA virus) and influenza virus (a negative-strand segmented RNA virus). Here, the L gene of vesicular stomatitis virus (VSV), a nonsegmented negative-sense RNA virus, was partially recoded based on codon pair bias. Totals of 858 and 623 silent mutations were introduced into a 5'-terminal segment of the viral L gene (designated L1) to create sequences containing either overrepresented or underrepresented codon pairs, designated L1(sdmax) and L1(min), respectively. Analysis revealed that recombinant VSV containing the L1(min) sequence could not be recovered, whereas the virus with the sdmax sequence showed a modest level of attenuation in cell culture. More strikingly, in mice the L1(sdmax) virus was almost as immunogenic as the parental strain but highly attenuated. Taken together, these results open a new road to attain a balance between VSV virulence and immunogenicity, which could serve as an example for the attenuation of other negative-strand, nonsegmented RNA viruses. Vesicular stomatitis virus (VSV) is the prototypic rhabdovirus in the order Mononegavirales. A wide range of human pathogens belong to this family. Using a unique computer algorithm and large-scale genome synthesis, we attempted to develop a live attenuated vaccine strain for VSV, which could be used as an antigen delivery platform for humans. Recombinant VSVs with distinct codon pair biases were rationally designed, constructed, and

  7. Attenuated Bordetella pertussis BPZE1 as a live vehicle for heterologous vaccine antigens delivery through the nasal route.

    Science.gov (United States)

    Li, Rui; Lim, Annabelle; Alonso, Sylvie

    2011-01-01

    Whereas the great majority of the current vaccines are delivered through the parenteral route, mucosal administration has been increasingly considered for controlling infection and preventing disease. Mucosal vaccination can trigger both humoral and cell-mediated protection, not only at the targeted mucosal surface, but also systemically. In this regard, nasal vaccination has shown great potential. The live attenuated strain of Bordetella pertussis, BPZE1, is particularly attractive and promising as a nasal vaccine delivery vector of heterologous antigen vaccine candidates. BPZE1 was originally developed as a live nasal pertussis vaccine candidate, and is currently undergoing phase I clinical trial in human (http://www.child-innovac.org). Highly adapted to the human respiratory tract and offering several potential protein carriers for presentation of the heterologous antigen vaccine candidates, BPZE1 represents an appealing platform for the development of live recombinant vaccines delivered via the nasal route that would confer simultaneous protection against pertussis and the targeted infectious disease(s).

  8. Temperature-sensitive mutations for live-attenuated Rift Valley fever vaccines: Implications from other RNA viruses

    Directory of Open Access Journals (Sweden)

    Shoko eNishiyama

    2015-08-01

    Full Text Available Rift Valley fever (RVF is a mosquito-borne zoonotic disease endemic to the African continent. RVF is characterized by high rate of abortions in ruminants and hemorrhagic fever, encephalitis or blindness in humans. RVF is caused by the Rift Valley fever virus (RVFV: genus Phlebovirus, family Bunyaviridae. Vaccination is the only known effective strategy to prevent the disease, but there are no licensed RVF vaccines available for humans. A live-attenuated vaccine candidate derived from the wild-type pathogenic Egyptian ZH548 strain, MP-12, has been conditionally licensed for veterinary use in the United States. MP-12 displays a temperature-sensitive (ts phenotype and does not replicate at 41oC. The ts mutation limits viral replication at a specific body temperature and may lead to an attenuation of the virus. Here we will review well-characterized ts mutations for RNA viruses, and further discuss the potential in designing novel live-attenuated vaccines for RVF.

  9. Use of RapidChek® SELECT™ Salmonella to detect shedding of live attenuated Salmonella enterica serovar Typhi vaccine strains.

    Science.gov (United States)

    Brenneman, Karen E; McDonald, Caitlin; Kelly-Aehle, Sandra M; Roland, Kenneth L; Curtiss, Roy

    2012-05-01

    Identification of individuals shedding Salmonella enterica serovar Typhi in stool is imperative during clinical trial safety evaluations. Recovery of live attenuated S. Typhi vaccine strains can be difficult because the mutations necessary for safety in humans often compromise survival in stringent selective enrichment media. RapidChek® SELECT™ Salmonella is a highly sensitive detection method for S. enterica species which utilizes a bacteriophage cocktail designed to reduce the growth of competitor microbes in mildly selective enrichment medium. Detection of Salmonella is enhanced by means of a Salmonella-specific antibody strip targeted to lipopolysaccharide. The RapidChek® SELECT™ Salmonella method was compared to conventional enrichment and plating methods to determine the most sensitive method for detecting attenuated S. Typhi strains in human stool samples. Although traditional enrichment strategies were more sensitive to the presence of wild-type S. Typhi, RapidChek® SELECT™ Salmonella was superior at detecting attenuated strains of S. Typhi. Strains containing a wide variety of attenuating mutations were detected with equal sensitivity as the wild type by RapidChek® SELECT™ Salmonella. The presence of Vi capsule or mutations which affected O-antigen synthesis (Δpmi, ΔgalE) did not decrease the sensitivity of the RapidChek® SELECT™ Salmonella assay.

  10. Pericardial Tamponade in an Adult Suffering from Acute Mumps Infection

    OpenAIRE

    Sascha Kahlfuss; Robert Rainer Flieger; Annette Mankertz; Kadir Yilmaz; Torsten Kai Roepke

    2016-01-01

    Here, we report a case of a 51-year-old man with acute pericardial tamponade requiring emergency pericardiocentesis after he suffered from sore throat, headache, malaise, and sweats for two weeks. Serological analyses revealed increased mumps IgM and IgG indicating an acute mumps infection whereas other bacterial and viral infections were excluded. In addition, MRI revealed atypical swelling of the left submandibular gland. Whereas mumps has become a rare entity in children due to comprehensi...

  11. Recombinant mumps virus as a cancer therapeutic agent

    OpenAIRE

    2016-01-01

    Mumps virus belongs to the family of Paramyxoviridae and has the potential to be an oncolytic agent. Mumps virus Urabe strain had been tested in the clinical setting as a treatment for human cancer four decades ago in Japan. These clinical studies demonstrated that mumps virus could be a promising cancer therapeutic agent that showed significant antitumor activity against various types of cancers. Since oncolytic virotherapy was not in the limelight until the beginning of the 21st century, th...

  12. Pericardial Tamponade in an Adult Suffering from Acute Mumps Infection

    Science.gov (United States)

    Flieger, Robert Rainer; Mankertz, Annette; Yilmaz, Kadir; Roepke, Torsten Kai

    2016-01-01

    Here, we report a case of a 51-year-old man with acute pericardial tamponade requiring emergency pericardiocentesis after he suffered from sore throat, headache, malaise, and sweats for two weeks. Serological analyses revealed increased mumps IgM and IgG indicating an acute mumps infection whereas other bacterial and viral infections were excluded. In addition, MRI revealed atypical swelling of the left submandibular gland. Whereas mumps has become a rare entity in children due to comprehensive vaccination regimens in western civilizations, our case highlights mumps as an important differential diagnosis also in adults, where the virus can induce life-threatening complications such as pericardial tamponade.

  13. Pericardial Tamponade in an Adult Suffering from Acute Mumps Infection

    Directory of Open Access Journals (Sweden)

    Sascha Kahlfuss

    2016-01-01

    Full Text Available Here, we report a case of a 51-year-old man with acute pericardial tamponade requiring emergency pericardiocentesis after he suffered from sore throat, headache, malaise, and sweats for two weeks. Serological analyses revealed increased mumps IgM and IgG indicating an acute mumps infection whereas other bacterial and viral infections were excluded. In addition, MRI revealed atypical swelling of the left submandibular gland. Whereas mumps has become a rare entity in children due to comprehensive vaccination regimens in western civilizations, our case highlights mumps as an important differential diagnosis also in adults, where the virus can induce life-threatening complications such as pericardial tamponade.

  14. Recombinant mumps virus as a cancer therapeutic agent.

    Science.gov (United States)

    Ammayappan, Arun; Russell, Stephen J; Federspiel, Mark J

    2016-01-01

    Mumps virus belongs to the family of Paramyxoviridae and has the potential to be an oncolytic agent. Mumps virus Urabe strain had been tested in the clinical setting as a treatment for human cancer four decades ago in Japan. These clinical studies demonstrated that mumps virus could be a promising cancer therapeutic agent that showed significant antitumor activity against various types of cancers. Since oncolytic virotherapy was not in the limelight until the beginning of the 21(st) century, the interest to pursue mumps virus for cancer treatment slowly faded away. Recent success stories of oncolytic clinical trials prompted us to resurrect the mumps virus and to explore its potential for cancer treatment. We have obtained the Urabe strain of mumps virus from Osaka University, Japan, which was used in the earlier human clinical trials. In this report we describe the development of a reverse genetics system from a major isolate of this Urabe strain mumps virus stock, and the construction and characterization of several recombinant mumps viruses with additional transgenes. We present initial data demonstrating these recombinant mumps viruses have oncolytic activity against tumor cell lines in vitro and some efficacy in preliminary pilot animal tumor models.

  15. Antigen-Specific lgA B Memory Cell Responses to Shigella Antigens Elicited in Volunteers Immunized with Live Attenuated Shigella flexneri 2a Oral Vaccine Candidates

    Science.gov (United States)

    2011-01-01

    cell responses to Shigella antigens elicited in volunteers immunized with live attenuated Shigella flexneri 2a oral vaccine candidates J.K. Simona,b... Shigella ;. B cell memory; Immunoglobulin lgA; Mucosal immunity Abstract We studied the induction of antigen-specific lgA memory B cells (BM) in...volunteers who received live attenuated Shigella flexneri 2a vaccines. Subjects ingested a single oral dose of 107 , 108 or 109 CFU of S. flexneri 2a with

  16. Protection of SA14-14-2 live attenuated Japanese encephalitis vaccine against the wild-type JE viruses

    Institute of Scientific and Technical Information of China (English)

    贾丽丽; 王志伟; 俞永新

    2003-01-01

    ObjectiveTo explore on the immunity of live attenuated Japanese Encephalitis (JE) vaccine(SA14-14-2) to different wild JE virus (JEV) strains. MethodsThe neutralizing effect of the vaccine against different wild JE virus strains was detected by plaque reduction neutralization test (PRNT), and the immunogenicity was studied on mice by vaccination -challenge protection test. In the PRNT , pooled sera from vaccinated human were tested against 10 strains of JEV , one isolated in Taiwan and 9 from other Asian countries.In the vaccination challenge test, mice received one dose of the live vaccine subcutaneously and were challenged intraperitoneally 14 days later against 22 JEV virus strains, 11 were isolated in China and the other 11 from Tailand, Vietnahailam, Indonesia, India, Philippines and Japan. ResultsThe protection rates to all the 22 challenge virus were 90%-100% when 340 PFU/0.1 ml vaccinate virus was administered. The neutralizing effect showed that all the JEV isolates many have neutralized by the sera. ConclusionSA14-14-2 live attenuated prepared with strain SA14-14-2 is broadly immunogenic and may have effective protection against in Asian JE affected countries.

  17. Early potent protection against heterologous SIVsmE660 challenge following live attenuated SIV vaccination in Mauritian cynomolgus macaques.

    Directory of Open Access Journals (Sweden)

    Neil Berry

    Full Text Available BACKGROUND: Live attenuated simian immunodeficiency virus (SIV vaccines represent the most effective means of vaccinating macaques against pathogenic SIV challenge. However, thus far, protection has been demonstrated to be more effective against homologous than heterologous strains. Immune correlates of vaccine-induced protection have also been difficult to identify, particularly those measurable in the peripheral circulation. METHODOLOGY/PRINCIPAL FINDINGS: Here we describe potent protection in 6 out of 8 Mauritian-derived cynomolgus macaques (MCM against heterologous virus challenge with the pathogenic, uncloned SIVsmE660 viral stock following vaccination with live attenuated SIVmac251/C8. MCM provided a characterised host genetic background with limited Major Histocompatibility Complex (MHC and TRIM5α allelic diversity. Early protection, observed as soon as 3 weeks post-vaccination, was comparable to that of 20 weeks vaccination. Recrudescence of vaccine virus was most pronounced in breakthrough cases where simultaneous identification of vaccine and challenge viruses by virus-specific PCR was indicative of active co-infection. Persistence of the vaccine virus in a range of lymphoid tissues was typified by a consistent level of SIV RNA positive cells in protected vaccinates. However, no association between MHC class I/II haplotype or TRIM5α polymorphism and study outcome was identified. CONCLUSION/SIGNIFICANCE: This SIV vaccine study, conducted in MHC-characterised MCM, demonstrated potent protection against the pathogenic, heterologous SIVsmE660 challenge stock after only 3 weeks vaccination. This level of protection against this viral stock by intravenous challenge has not been hitherto observed. The mechanism(s of protection by vaccination with live attenuated SIV must account for the heterologous and early protection data described in this study, including those which relate to the innate immune system.

  18. 78 FR 43219 - Prospective Grant of Exclusive License: Live Attenuated Dengue Tetravalent Vaccine Containing a...

    Science.gov (United States)

    2013-07-19

    ... means for prevention of dengue infection and dengue hemorrhagic fever (DHF) by immunization with... Dengue Tetravalent Vaccine Containing a Common 30 Nucleotide Deletion in the 3'-UTR of Dengue Types 1, 2... et al., ``Development of Mutations Useful for Attenuating Dengue Viruses and Chimeric Dengue...

  19. Goal directed preemptive ephedrine attenuates the reperfusion syndrome during adult living donor liver transplantation

    Directory of Open Access Journals (Sweden)

    Nirmeen A. Fayed

    2014-04-01

    Conclusion: The preemptive goal directed titration of ephedrine against a target MAP pre-reperfusion could decrease the incidence of PRS by 40%, attenuated the hypotensive response to reperfusion and decreased the need for postreperfusion vasoconstrictor support without over shooting of any of the monitored hemodynamic indices.

  20. A Bioinformatics Method for the Design of Live Attenuated Virus Vaccine Utilizing Host MicroRNA Response Elements.

    Science.gov (United States)

    Wichadakul, Duangdao

    2016-01-01

    The host microRNA machinery has been employed to control viral replication. To improve safety for live attenuated virus vaccines, the binding sites of the host microRNAs, so-called microRNA response elements (MREs), were incorporated into the virus sequences. These MREs were typically designed for a specific host microRNA and virus sequence with the effectiveness evaluated by experimental trials. Here, we describe a computational flow that can be used to simultaneously design and prioritize the effective MREs in large-scale.

  1. EFFECT OF VARIOUS STABILIZERS ON TITRE OF LYOPHILIZED LIVE-ATTENUATED PESTE DES PETITS RUMINANTS (PPR VACCINE

    Directory of Open Access Journals (Sweden)

    M. ASIM, A. RASHID AND A. H. CHAUDHARY

    2008-12-01

    Full Text Available Lyophilization stabilizes the biological materials by using two overlapping drying procedure i.e. primary drying by sublimation of the ice crystal from frozen material and secondary drying or desorption by evaporation of the free water adsorbed into the dried product. Three different stabilizers i.e. lactalbumin hydrolysate-sucrose, Weybridge medium and lactalbumin hydrolysate-manitol were used to lyophilize the Peste des petits ruminants (PPR vaccine. Titre of live-attenuated PPR cell culture experimental vaccine was studied after lyophilization which revealed that PPR vaccine lyophilized with Weybridge medium was more stable and maintained the virus titre longer than rest of stabilizers used in the study.

  2. Synergistic Internal Ribosome Entry Site/MicroRNA-Based Approach for Flavivirus Attenuation and Live Vaccine Development

    Directory of Open Access Journals (Sweden)

    Konstantin A. Tsetsarkin

    2017-04-01

    Full Text Available The recent emergence of Zika virus underscores the need for new strategies for a rapid development of safe flavivirus vaccines. Using another flavivirus (Langat virus [LGTV] that belongs to the group of tick-borne flaviviruses as a model, we describe a dual strategy for virus attenuation which synergistically accesses the specificity of microRNA (miRNA genome targeting and the effectiveness of internal ribosome entry site (IRES insertion. To increase the stability and immunogenicity of bicistronic LGTVs, we developed a novel approach in which the capsid (C protein gene was relocated into the 3′ noncoding region (NCR and expressed under translational control from an IRES. Engineered bicistronic LGTVs carrying multiple target sequences for brain-specific miRNAs were stable in Vero cells and induced adaptive immunity in mice. Importantly, miRNA-targeted bicistronic LGTVs were not pathogenic for either newborn mice after intracranial inoculation or adult immunocompromised mice (SCID or type I interferon receptor knockout after intraperitoneal injection. Moreover, bicistronic LGTVs were restricted for replication in tick-derived cells, suggesting an interruption of viral transmission in nature by arthropod vectors. This approach is suitable for reliable attenuation of many flaviviruses and may enable development of live attenuated flavivirus vaccines.

  3. Rational Design of Human Metapneumovirus Live Attenuated Vaccine Candidates by Inhibiting Viral mRNA Cap Methyltransferase

    Science.gov (United States)

    Zhang, Yu; Wei, Yongwei; Zhang, Xiaodong; Cai, Hui; Niewiesk, Stefan

    2014-01-01

    ABSTRACT The paramyxoviruses human respiratory syncytial virus (hRSV), human metapneumovirus (hMPV), and human parainfluenza virus type 3 (hPIV3) are responsible for the majority of pediatric respiratory diseases and inflict significant economic loss, health care costs, and emotional burdens. Despite major efforts, there are no vaccines available for these viruses. The conserved region VI (CR VI) of the large (L) polymerase proteins of paramyxoviruses catalyzes methyltransferase (MTase) activities that typically methylate viral mRNAs at positions guanine N-7 (G-N-7) and ribose 2′-O. In this study, we generated a panel of recombinant hMPVs carrying mutations in the S-adenosylmethionine (SAM) binding site in CR VI of L protein. These recombinant viruses were specifically defective in ribose 2′-O methylation but not G-N-7 methylation and were genetically stable and highly attenuated in cell culture and viral replication in the upper and lower respiratory tracts of cotton rats. Importantly, vaccination of cotton rats with these recombinant hMPVs (rhMPVs) with defective MTases triggered a high level of neutralizing antibody, and the rats were completely protected from challenge with wild-type rhMPV. Collectively, our results indicate that (i) amino acid residues in the SAM binding site in the hMPV L protein are essential for 2′-O methylation and (ii) inhibition of mRNA cap MTase can serve as a novel target to rationally design live attenuated vaccines for hMPV and perhaps other paramyxoviruses, such as hRSV and hPIV3. IMPORTANCE Human paramyxoviruses, including hRSV, hMPV, and hPIV3, cause the majority of acute upper and lower respiratory tract infections in humans, particularly in infants, children, the elderly, and immunocompromised individuals. Currently, there is no licensed vaccine available. A formalin-inactivated vaccine is not suitable for these viruses because it causes enhanced lung damage upon reinfection with the same virus. A live attenuated vaccine

  4. Generation and Characterization of Live Attenuated Influenza A(H7N9) Candidate Vaccine Virus Based on Russian Donor of Attenuation

    Science.gov (United States)

    Shcherbik, Svetlana; Pearce, Nicholas; Balish, Amanda; Jones, Joyce; Thor, Sharmi; Davis, Charles Todd; Pearce, Melissa; Tumpey, Terrence; Cureton, David; Chen, Li-Mei; Villanueva, Julie; Bousse, Tatiana L.

    2015-01-01

    Background Avian influenza A (H7N9) virus has emerged recently and continues to cause severe disease with a high mortality rate in humans prompting the development of candidate vaccine viruses. Live attenuated influenza vaccines (LAIV) are 6:2 reassortant viruses containing the HA and NA gene segments from wild type influenza viruses to induce protective immune responses and the six internal genes from Master Donor Viruses (MDV) to provide temperature sensitive, cold-adapted and attenuated phenotypes. Methodology/Principal Findings LAIV candidate A/Anhui/1/2013(H7N9)-CDC-LV7A (abbreviated as CDC-LV7A), based on the Russian MDV, A/Leningrad/134/17/57 (H2N2), was generated by classical reassortment in eggs and retained MDV temperature-sensitive and cold-adapted phenotypes. CDC-LV7A had two amino acid substitutions N123D and N149D (H7 numbering) in HA and one substitution T10I in NA. To evaluate the role of these mutations on the replication capacity of the reassortants in eggs, the recombinant viruses A(H7N9)RG-LV1 and A(H7N9)RG-LV2 were generated by reverse genetics. These changes did not alter virus antigenicity as ferret antiserum to CDC-LV7A vaccine candidate inhibited hemagglutination by homologous A(H7N9) virus efficiently. Safety studies in ferrets confirmed that CDC-LV7A was attenuated compared to wild-type A/Anhui/1/2013. In addition, the genetic stability of this vaccine candidate was examined in eggs and ferrets by monitoring sequence changes acquired during virus replication in the two host models. No changes in the viral genome were detected after five passages in eggs. However, after ten passages additional mutations were detected in the HA gene. The vaccine candidate was shown to be stable in the ferret model; post-vaccination sequence data analysis showed no changes in viruses collected in nasal washes present at day 5 or day 7. Conclusions/Significance Our data indicate that the A/Anhui/1/2013(H7N9)-CDC-LV7A reassortant virus is a safe and

  5. Generation and Characterization of Live Attenuated Influenza A(H7N9 Candidate Vaccine Virus Based on Russian Donor of Attenuation.

    Directory of Open Access Journals (Sweden)

    Svetlana Shcherbik

    Full Text Available Avian influenza A (H7N9 virus has emerged recently and continues to cause severe disease with a high mortality rate in humans prompting the development of candidate vaccine viruses. Live attenuated influenza vaccines (LAIV are 6:2 reassortant viruses containing the HA and NA gene segments from wild type influenza viruses to induce protective immune responses and the six internal genes from Master Donor Viruses (MDV to provide temperature sensitive, cold-adapted and attenuated phenotypes.LAIV candidate A/Anhui/1/2013(H7N9-CDC-LV7A (abbreviated as CDC-LV7A, based on the Russian MDV, A/Leningrad/134/17/57 (H2N2, was generated by classical reassortment in eggs and retained MDV temperature-sensitive and cold-adapted phenotypes. CDC-LV7A had two amino acid substitutions N123D and N149D (H7 numbering in HA and one substitution T10I in NA. To evaluate the role of these mutations on the replication capacity of the reassortants in eggs, the recombinant viruses A(H7N9RG-LV1 and A(H7N9RG-LV2 were generated by reverse genetics. These changes did not alter virus antigenicity as ferret antiserum to CDC-LV7A vaccine candidate inhibited hemagglutination by homologous A(H7N9 virus efficiently. Safety studies in ferrets confirmed that CDC-LV7A was attenuated compared to wild-type A/Anhui/1/2013. In addition, the genetic stability of this vaccine candidate was examined in eggs and ferrets by monitoring sequence changes acquired during virus replication in the two host models. No changes in the viral genome were detected after five passages in eggs. However, after ten passages additional mutations were detected in the HA gene. The vaccine candidate was shown to be stable in the ferret model; post-vaccination sequence data analysis showed no changes in viruses collected in nasal washes present at day 5 or day 7.Our data indicate that the A/Anhui/1/2013(H7N9-CDC-LV7A reassortant virus is a safe and genetically stable candidate vaccine virus that is now available for

  6. Rational design of genetically stable, live-attenuated poliovirus vaccines of all three serotypes: relevance to poliomyelitis eradication.

    Science.gov (United States)

    Macadam, Andrew J; Ferguson, Geraldine; Stone, David M; Meredith, Janet; Knowlson, Sarah; Auda, Ghazi; Almond, Jeffrey W; Minor, Philip D

    2006-09-01

    The global eradication of poliomyelitis caused by wild-type virus is likely to be completed within the next few years, despite immense logistic and political difficulties, and may ultimately be followed by the cessation of vaccination. However, the existing live-attenuated vaccines have the potential to revert to virulence, causing occasional disease, and viruses can be shed by immunocompromised individuals for prolonged periods of time. Moreover, several outbreaks of poliomyelitis have been shown to be caused by viruses derived from the Sabin vaccine strains. The appearance of such strains depends on the prevailing circumstances but poses a severe obstacle to strategies for stopping vaccination. Vaccine strains that are incapable of reversion at a measurable rate would provide a possible solution. Here, we describe the constructions of strains of type 3 poliovirus that are stabilized by the introduction of four mutations in the 5' noncoding region compared to the present vaccine. The strains are genetically and phenotypically stable under conditions where the present vaccine loses the attenuating mutation in the 5' noncoding region completely. Type 1 and type 2 strains in which the entire 5' noncoding regions of Sabin 1 and Sabin 2 were replaced exactly with that of one of the type 3 strains were also constructed. The genetic stability of 5' noncoding regions of these viruses matched that of the type 3 strains, but significant phenotypic reversion occurred, illustrating the potential limitations of a rational approach to the genetic stabilization of live RNA virus vaccines.

  7. Suppressing active replication of a live attenuated simian immunodeficiency virus vaccine does not abrogate protection from challenge

    Energy Technology Data Exchange (ETDEWEB)

    Gabriel, Benjamin; Fiebig, Uwe; Hohn, Oliver [Robert Koch-Institut, Berlin (Germany); Plesker, Roland; Coulibaly, Cheick; Cichutek, Klaus; Mühlebach, Michael D. [Paul-Ehrlich-Institut, Langen (Germany); Bannert, Norbert; Kurth, Reinhard [Robert Koch-Institut, Berlin (Germany); Norley, Stephen, E-mail: NorleyS@rki.de [Robert Koch-Institut, Berlin (Germany)

    2016-02-15

    Although safety concerns preclude the use of live attenuated HIV vaccines in humans, they provide a useful system for identifying the elusive correlates of protective immunity in the SIV/macaque animal model. However, a number of pieces of evidence suggest that protection may result from prior occupancy of susceptible target cells by the vaccine virus rather than the immune response. To address this, we developed a Nef-deletion variant of an RT-SHIV whose active replication could be shut off by treatment with RT-inhibitors. Groups of macaques were inoculated with the ∆Nef-RT-SHIV and immune responses allowed to develop before antiretroviral treatment and subsequent challenge with wild-type SIVmac239. Vaccinated animals either resisted infection fully or significantly controlled the subsequent viremia. However, there was no difference between animals undergoing replication of the vaccine virus and those without. This strongly suggests that competition for available target cells does not play a role in protection. - Highlights: • A Nef-deleted RT-SHIV was used as a live attenuated vaccine in macaques. • Vaccine virus replication was shut down to investigate its role in protection. • Ongoing vaccine virus replication did not appear to be necessary for protection. • An analysis of T- and B-cell responses failed to identify a correlate of protection.

  8. A Yersinia pestis YscN ATPase mutant functions as a live attenuated vaccine against bubonic plague in mice.

    Science.gov (United States)

    Bozue, Joel; Cote, Christopher K; Webster, Wendy; Bassett, Anthony; Tobery, Steven; Little, Stephen; Swietnicki, Wieslaw

    2012-07-01

    Yersinia pestis is the causative agent responsible for bubonic and pneumonic plague. The bacterium uses the pLcr plasmid-encoded type III secretion system to deliver virulence factors into host cells. Delivery requires ATP hydrolysis by the YscN ATPase encoded by the yscN gene also on pLcr. A yscN mutant was constructed in the fully virulent CO92 strain containing a nonpolar, in-frame internal deletion within the gene. We demonstrate that CO92 with a yscN mutation was not able to secrete the LcrV protein (V-Antigen) and attenuated in a subcutaneous model of plague demonstrating that the YscN ATPase was essential for virulence. However, if the yscN mutant was complemented with a functional yscN gene in trans, virulence was restored. To evaluate the mutant as a live vaccine, Swiss-Webster mice were vaccinated twice with the ΔyscN mutant at varying doses and were protected against bubonic plague in a dose-dependent manner. Antibodies to F1 capsule but not to LcrV were detected in sera from the vaccinated mice. These preliminary results suggest a proof-of-concept for an attenuated, genetically engineered, live vaccine effective against bubonic plague. Published 2012. This article is a US Government work and is in the public domain in the USA.

  9. Live attenuated Francisella novicida vaccine protects against Francisella tularensis pulmonary challenge in rats and non-human primates.

    Directory of Open Access Journals (Sweden)

    Ping Chu

    2014-10-01

    Full Text Available Francisella tularensis causes the disease tularemia. Human pulmonary exposure to the most virulent form, F. tularensis subsp. tularensis (Ftt, leads to high morbidity and mortality, resulting in this bacterium being classified as a potential biothreat agent. However, a closely-related species, F. novicida, is avirulent in healthy humans. No tularemia vaccine is currently approved for human use. We demonstrate that a single dose vaccine of a live attenuated F. novicida strain (Fn iglD protects against subsequent pulmonary challenge with Ftt using two different animal models, Fischer 344 rats and cynomolgus macaques (NHP. The Fn iglD vaccine showed protective efficacy in rats, as did a Ftt iglD vaccine, suggesting no disadvantage to utilizing the low human virulent Francisella species to induce protective immunity. Comparison of specific antibody profiles in vaccinated rat and NHP sera by proteome array identified a core set of immunodominant antigens in vaccinated animals. This is the first report of a defined live attenuated vaccine that demonstrates efficacy against pulmonary tularemia in a NHP, and indicates that the low human virulence F. novicida functions as an effective tularemia vaccine platform.

  10. [History of development of the live poliomyelitis vaccine from Sabin attenuated strains in 1959 and idea of poliomyelitis eradication].

    Science.gov (United States)

    Lashkevich, V A

    2013-01-01

    In 1958 Poliomyelitis Institute in Moscow and Institute of Experimental Medicine in St. Petersburg received from A. Sabin the attenuated strains of poliomyelitis virus. The characteristics of the strains were thoroughly studied by A. A. Smorodintsev and coworkers. They found that the virulence of the strains fluctuated slightly in 10 consecutive passages through the intestine of the non-immune children. A part of the Sabin material was used by A. A. Smorodintsev and M. P. Chumakov in the beginning of 1959 for immunizing approximately 40000 children in Estonia, Lithuania, and Latvia. Epidemic poliomyelitis rate in these republics decreased from approximately 1000 cases yearly before vaccination to less than 20 in the third quarter of 1959. This was a convincing proof of the efficacy and safety of the vaccine from the attenuated Sabin strains. In 1959, according to A. Sabin's recommendation, a technology of live vaccine production was developed at the Poliomyelitis Institute, and several experimental lots of vaccine were prepared. In the second part of 1959, 13.5 million children in USSR were immunized. The epidemic poliomyelitis rate decreased 3-5 times in different regions without paralytic cases, which could be attributed to the vaccination. These results were the final proof of high efficiency and safety of live poliomyelitis vaccine from the attenuated Sabin strains. Based on these results, A. Sabin and M. P. Chumakov suggested in 1960 the idea of poliomyelitis eradication using mass immunization of children with live vaccine. 72 million persons up to 20 years old were vaccinated in USSR in 1960 with a 5 times drop in the paralytic rate. 50-year-long use of live vaccine results in poliomyelitis eradication in almost all countries worldwide. More than 10 million children were rescued from the death and palsy. Poliomyelitis eradication in a few countries where it still exists depends not on medical services but is defined by the attitude of their leaders to fight

  11. Development of a human live attenuated West Nile infectious DNA vaccine: Suitability of attenuating mutations found in SA14-14-2 for WN vaccine design

    Energy Technology Data Exchange (ETDEWEB)

    Yamshchikov, Vladimir, E-mail: yaximik@gmail.com; Manuvakhova, Marina; Rodriguez, Efrain

    2016-01-15

    Direct attenuation of West Nile (WN) virus strain NY99 for the purpose of vaccine development is not feasible due to its high virulence and pathogenicity. Instead, we created highly attenuated chimeric virus W1806 with the serological identity of NY99. To further attenuate W1806, we investigated effects of mutations found in Japanese encephalitis virus vaccine SA14-14-2. WN viruses carrying all attenuating mutations lost infectivity in mammalian, but not in mosquito cells. No single reversion restored infectivity in mammalian cells, although increased infectivity in mosquito cells was observed. To identify a subset of mutations suitable for further attenuation of W1806, we analyzed effects of E{sub 138}K and K{sub 279}M changes on virulence, growth properties, and immunogenicity of derivatized W956, from which chimeric W1806 inherited its biological properties and attenuation profile. Despite strong dominant attenuating effect, introduction of only two mutations was not sufficient for attenuating W1806 to the safety level acceptable for human use. - Highlights: • Further attenuation of a WN vaccine precursor is outlined. • Effect of SA14-14-2 attenuating mutations is tested. • Mechanism of attenuation is proposed and illustrated. • The need for additional attenuating mutations is justified.

  12. [Attenuation of a strain of rinderpest virus: potential homologous live vaccine].

    Science.gov (United States)

    Diallo, A; Taylor, W P; Lefèvre, P C; Provost, A

    1989-01-01

    Peste des petits ruminants (PPR) is a highly contagious disease of small ruminants frequently associated with severe mortality in these hosts. In countries where it occurs, PPR represents an important constraint to the improved productivity of sheep and goats. Until now the only way to combat this plague has been the use of heterologous rinderpest vaccine; all attempts to develop a homologous vaccine have ended in failure. The present communication describes the attenuation of the Nigerian strain PPRV Nig 75/1 by serial passage in Vero cells. The avirulent virus obtained has the same characteristics as Plowright and Ferris' rinderpest vaccine. The virus is advanced as a potential homologous vaccine against PPR.

  13. SENSORY HEARING LOSS IN CHILDREN WITH MUMPS INFECTION

    Directory of Open Access Journals (Sweden)

    S. Noorbaksh

    2006-10-01

    Full Text Available Objective:Mumps infection is endemic in Iran and mumps parotiditis is acommon disease in Iranian children. There has been a dramaticdecrease in the worldwide incidence of mumps since the introductionand use in 1968 of the very effective and inexpensive mumps vaccine.In Iran probably due to a higher percentage of unvaccinated youngpersons <15yr, the incidence rate of mumps infection and its sequelaare higher in comparison to corresponding data from developedcountries prior to comprehensive vaccination programs. The aim ofthe study was to investigate the effects of the mumps virus on cochlearfunction and to determine the frequency of related Sensory NeuralHearing Loss (SNHL in children.Material& Methods:This descriptive case-series study was conducted in 94children, agedless than 14 years, hospitalized between 1999 and 2001, in thepediatric ward of the Hazrat Rasool Hospital in Tehran. All patientswith documented mumps infection (specific mumps-IgM antibodywere evaluated twice for audiometeric function on the basis ofdiagnostic parameters for sensory neural hearing loss; the first evaluationwas done on admission and the second three weeks later. 54 patients(age range 1-14y, mean age 4.83±3.93, male: female ratio30:24were studied in two years.Results:The highest incidence of mumps was seen in winter (37% and spring(28% and the lowest in summer (13%. Specific IgM antibody formumps virus was detected in 74 children. Comprehensive audiologicevaluation was done in 54 patients at admission and again 3 weekslater. SNHL was detected in 7.2% of patients; the 4.4% incidence ofSNHL in this study was higher than in other studies in developedcountries prior to comprehensive vaccination programs.Conclusion:Implementation of comprehensive vaccination programs in youngIranians could dramatically reduce the burden and costs imposed bythe infection and its sequelae.Keywords: Mumps infection ;SNLH(sensorineural hearing loss;Mumpsvaccination

  14. Immunogenicity and protective efficacy of an elastase-dependent live attenuated swine influenza virus vaccine administered intranasally in pigs.

    Science.gov (United States)

    Masic, Aleksandar; Lu, Xinya; Li, Junwei; Mutwiri, George K; Babiuk, Lorne A; Brown, Earl G; Zhou, Yan

    2010-10-01

    Influenza A virus is an important respiratory pathogen of swine that causes significant morbidity and economic impact on the swine industry. Vaccination is the first choice for prevention and control of influenza infections. Live attenuated influenza vaccines (LAIV) are approved for use in humans and horses and their application provides broad protective immunity, however no LAIV against swine influenza virus (SIV) exists in the market. Previously we reported that an elastase-dependent mutant SIV A/Sw/Sk-R345V (R345V) derived from A/Sw/Saskatchewan/18789/02 (H1N1) (SIV/Sk02) is highly attenuated in pigs. Two intratracheal administrations of R345V induced strong cell-mediated and humoral immune responses and provided a high degree of protection to antigenically different SIV infection in pigs. Here we evaluated the immunogenicity and the protective efficacy of R345V against SIV infection by intranasal administration, the more practical route for vaccination of pigs in the field. Our data showed that intranasally administered R345V live vaccine is capable of inducing strong antigen-specific IFN-γ response from local tracheo-bronchial lymphocytes and antibody responses in serum and respiratory mucosa after two applications. Intranasal vaccination of R345V provided pigs with complete protection not only from parental wild type virus infection, but also from homologous antigenic variant A/Sw/Indiana/1726/88 (H1N1) infection. Moreover, intranasal administration of R345V conferred partial protection from heterologous subtypic H3N2 SIV infection in pigs. Thus, R345V elastase-dependent mutant SIV can serve as a live vaccine against antigenically different swine influenza viruses in pigs.

  15. Safety of a Live Attenuated Infectious Bovine Rhinotracheitis Vaccine IBRV LNM Strain

    Institute of Scientific and Technical Information of China (English)

    Guo; Li; Wang; Wei; Zhang; Shuqin; Cheng; Shipeng; Wu; Hua

    2014-01-01

    The paper was to evaluate the vaccine safety,and to prevent public health risk due to virus spread,the approach vaccination of was adopted in this research; and neck intramuscular injection of IBRV LNM attenuated vaccine strain was carried out. Blind passage for three generations in animal has tested the reversion risk to virulence. A total of 14 healthy and weaning cows at 6- 8 month old were divided into three groups. The 1st reversion of virulence trials used 105. 0TCID50/mL neck intramuscular injection of IBRV LNM attenuated vaccine strain. Then,the nose swab samples were collected for continuous 14 days. After passed through 0. 45 μm filter membrane,nasal swabs mixture was prepared as the virulence test inoculum for next generation. The body temperature was detected and clinical observation was carried out for continuous 14 days after inoculation. The inoculation dose was 1ml / cattle. Blood was collected on the 0 and 14 thdays of animal vaccination. After serum isolation,it was used for the antibody detection of serum. Research results showed that no virus was isolated from the nasal swabs from the F2 generation; vaccinated animals did not show any clinical signs of IBR; serological testing of IBRV antibody was negative,which indicated that the strain-inoculated animals did had reversion of virulence in all three generations.

  16. African Green Monkeys Recapitulate the Clinical Experience with Replication of Live Attenuated Pandemic Influenza Virus Vaccine Candidates

    Science.gov (United States)

    Matsuoka, Yumiko; Suguitan, Amorsolo; Orandle, Marlene; Paskel, Myeisha; Boonnak, Kobporn; Gardner, Donald J.; Feldmann, Friederike; Feldmann, Heinz; Marino, Michael; Jin, Hong; Kemble, George

    2014-01-01

    ABSTRACT Live attenuated cold-adapted (ca) H5N1, H7N3, H6N1, and H9N2 influenza vaccine viruses replicated in the respiratory tract of mice and ferrets, and 2 doses of vaccines were immunogenic and protected these animals from challenge infection with homologous and heterologous wild-type (wt) viruses of the corresponding subtypes. However, when these vaccine candidates were evaluated in phase I clinical trials, there were inconsistencies between the observations in animal models and in humans. The vaccine viruses did not replicate well and immune responses were variable in humans, even though the study subjects were seronegative with respect to the vaccine viruses before vaccination. Therefore, we sought a model that would better reflect the findings in humans and evaluated African green monkeys (AGMs) as a nonhuman primate model. The distribution of sialic acid (SA) receptors in the respiratory tract of AGMs was similar to that in humans. We evaluated the replication of wt and ca viruses of avian influenza (AI) virus subtypes H5N1, H6N1, H7N3, and H9N2 in the respiratory tract of AGMs. All of the wt viruses replicated efficiently, while replication of the ca vaccine viruses was restricted to the upper respiratory tract. Interestingly, the patterns and sites of virus replication differed among the different subtypes. We also evaluated the immunogenicity and protective efficacy of H5N1, H6N1, H7N3, and H9N2 ca vaccines. Protection from wt virus challenge correlated well with the level of serum neutralizing antibodies. Immune responses were slightly better when vaccine was delivered by both intranasal and intratracheal delivery than when it was delivered intranasally by sprayer. We conclude that live attenuated pandemic influenza virus vaccines replicate similarly in AGMs and human subjects and that AGMs may be a useful model to evaluate the replication of ca vaccine candidates. IMPORTANCE Ferrets and mice are commonly used for preclinical evaluation of influenza

  17. Revaccination with Live Attenuated Vaccines Confer Additional Beneficial Nonspecific Effects on Overall Survival

    DEFF Research Database (Denmark)

    Benn, Christine S; Fisker, Ane B; Whittle, Hilton C

    2016-01-01

    BACKGROUND: Live vaccines against measles (MV), tuberculosis (BCG), polio (OPV) and smallpox reduce mortality more than explained by target-disease prevention. The beneficial nonspecific effects (NSEs) of MV are strongest when MV is given in presence of maternal antibodies. We therefore hypothesi......BACKGROUND: Live vaccines against measles (MV), tuberculosis (BCG), polio (OPV) and smallpox reduce mortality more than explained by target-disease prevention. The beneficial nonspecific effects (NSEs) of MV are strongest when MV is given in presence of maternal antibodies. We therefore....... In a quasi-experimental study two doses before and after 9months compared with one dose of MV after 9months of age reduced mortality by 59% (25-81%). BCG-revaccination significantly enhanced BCG's effect against overall child mortality in two RCTs. In a natural experiment study of OPV campaigns over a 13......-year-period in Guinea-Bissau, each additional dose of OPV was associated with a 13% (4-21%) reduction in mortality rate. The beneficial NSEs of smallpox vaccination for survival increased significantly with the number of smallpox vaccination scars. INTERPRETATION: Revaccination with live vaccines led...

  18. WHO working group on the quality, safety and efficacy of japanese encephalitis vaccines (live attenuated) for human use, Bangkok, Thailand, 21-23 February 2012.

    Science.gov (United States)

    Trent, Dennis W; Minor, Philip; Jivapaisarnpong, Teeranart; Shin, Jinho

    2013-11-01

    Japanese encephalitis (JE) is one of the most important viral encephalitides in Asia. Two live-attenuated vaccines have been developed and licensed for use in countries in the region. Given the advancement of immunization of humans with increasing use of live-attenuated vaccines to prevent JE, there is increased interest to define quality standards for their manufacture, testing, nonclinical studies, and clinical studies to assess their efficacy and safety in humans. To this end, WHO convened a meeting with a group of international experts in February 2012 to develop guidelines for evaluating the quality, safety and efficacy of live-attenuated JE virus vaccines for prevention of human disease. This report summarizes collective views of the participants on scientific and technical issues that need to be considered in the guidelines. Copyright © 2013. Published by Elsevier Ltd.. All rights reserved.

  19. Glycolipid antigens for treating hepatic colorectal cancer metastases and their effect on the therapeutic efficacy of live attenuated Listeria monocytogenes.

    Science.gov (United States)

    Olino, Kelly; Edil, Barish H; Meckel, Kristen F; Pan, Xiaoyu; Thuluvath, Avesh; Pardoll, Drew M; Schulick, Richard D; Yoshimura, Kiyoshi; Weber, Walter P

    2012-05-01

    Previous work demonstrated that a subset of natural killer T cells in mice decreased the antitumor efficacy of live attenuated Listeria monocytogenes where the actin A and internalin B genes were genetically deleted (LMD) against murine hepatic colorectal cancer metastases. Therefore, we hypothesized that the use of specific glycolipids known to selectively stimulate natural killer T-cell subsets used alone or co-administered with LMD would increase survival. We found that early or multiple administrations of glycolipids after tumor challenge had a strong impact on survival with or without LMD. Solitary administration or treatment given later was less efficacious but still showed a strong trend toward enhancing the antitumor activity of LMD. These results underscore the potential of glycolipids in the treatment of hepatic metastases and encourage further investigations into the immunomodulation of natural killer T cells to enhance the antitumor activity of LMD.

  20. Development of a human live attenuated West Nile infectious DNA vaccine: conceptual design of the vaccine candidate.

    Science.gov (United States)

    Yamshchikov, Vladimir

    2015-10-01

    West Nile virus has become an important epidemiological problem attracting significant attention of health authorities, mass media, and the public. Although there are promising advancements toward addressing the vaccine need, the perspectives of the commercial availability of the vaccine remain uncertain. To a large extent this is due to lack of a sustained interest for further commercial development of the vaccines already undergoing the preclinical and clinical development, and a predicted insignificant cost effectiveness of mass vaccination. There is a need for a safe, efficacious and cost effective vaccine, which can improve the feasibility of a targeted vaccination program. In the present report, we summarize the background, the rationale, and the choice of the development pathway that we selected for the design of a live attenuated human West Nile vaccine in a novel infectious DNA format.

  1. Multiple antigens of Yersinia pestis delivered by live recombinant attenuated Salmonella vaccine strains elicit protective immunity against plague.

    Science.gov (United States)

    Sanapala, Shilpa; Rahav, Hannah; Patel, Hetal; Sun, Wei; Curtiss, Roy

    2016-05-05

    Based on our improved novel Salmonella vaccine delivery platform, we optimized the recombinant attenuated Salmonella typhimurium vaccine (RASV) χ12094 to deliver multiple Yersinia pestis antigens. These included LcrV196 (amino acids, 131-326), Psn encoded on pYA5383 and F1 encoded in the chromosome, their synthesis did not cause adverse effects on bacterial growth. Oral immunization with χ12094(pYA5383) simultaneously stimulated high antibody titers to LcrV, Psn and F1 in mice and presented complete protection against both subcutaneous (s.c.) and intranasal (i.n.) challenges with high lethal doses of Y. pestis CO92. Moreover, no deaths or other disease symptoms were observed in SCID mice orally immunized with χ12094(pYA5383) over a 60-day period. Therefore, the trivalent S. typhimurium-based live vaccine shows promise for a next-generation plague vaccine. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Evaluation of eight live attenuated vaccine candidates for protection against challenge with virulent Mycobacterium avium subspecies paratuberculosis in mice.

    Science.gov (United States)

    Bannantine, John P; Everman, Jamie L; Rose, Sasha J; Babrak, Lmar; Katani, Robab; Barletta, Raúl G; Talaat, Adel M; Gröhn, Yrjö T; Chang, Yung-Fu; Kapur, Vivek; Bermudez, Luiz E

    2014-01-01

    Johne's disease is caused by Mycobacterium avium subsp. paratuberculosis (MAP), which results in serious economic losses worldwide in farmed livestock such as cattle, sheep, and goats. To control this disease, an effective vaccine with minimal adverse effects is needed. In order to identify a live vaccine for Johne's disease, we evaluated eight attenuated mutant strains of MAP using a C57BL/6 mouse model. The persistence of the vaccine candidates was measured at 6, 12, and 18 weeks post vaccination. Only strains 320, 321, and 329 colonized both the liver and spleens up until the 12-week time point. The remaining five mutants showed no survival in those tissues, indicating their complete attenuation in the mouse model. The candidate vaccine strains demonstrated different levels of protection based on colonization of the challenge strain in liver and spleen tissues at 12 and 18 weeks post vaccination. Based on total MAP burden in both tissues at both time points, strain 315 (MAP1566::Tn5370) was the most protective whereas strain 318 (intergenic Tn5367 insertion between MAP0282c and MAP0283c) had the most colonization. Mice vaccinated with an undiluted commercial vaccine preparation displayed the highest bacterial burden as well as enlarged spleens indicative of a strong infection. Selected vaccine strains that showed promise in the mouse model were moved forward into a goat challenge model. The results suggest that the mouse trial, as conducted, may have a relatively poor predictive value for protection in a ruminant host such as goats.

  3. Generation of a safe and effective live viral vaccine by virus self-attenuation using species-specific artificial microRNA.

    Science.gov (United States)

    Li, Junwei; Arévalo, Maria T; Diaz-Arévalo, Diana; Chen, Yanping; Choi, Jang-Gi; Zeng, Mingtao

    2015-06-10

    Vaccination with live attenuated vaccines (LAVs) is an effective way for prevention of infectious disease. While several methods are employed to create them, efficacy and safety are still a challenge. In this study, we evaluated the feasibility of creating a self-attenuated RNA virus expressing a functional species-specific artificial microRNA. Using influenza virus as a model, we produced an attenuated virus carrying a mammalian-specific miR-93 expression cassette that expresses a viral nucleoprotein (NP)-specific artificial microRNA from an insertion site within the non-structural (NS) gene segment. The resulting engineered live-attenuated influenza virus, PR8-amiR-93NP, produced mature and functional artificial microRNA against NP in mammalian cells, but not in avian cells. Furthermore, PR8-amiR-93NP was attenuated by 10(4) fold in mice compared with its wild-type counterpart. Importantly, intranasal immunization with PR8-amiR-93NP conferred cross-protective immunity against heterologous influenza virus strains. In short, this method provides a safe and effective platform for creation of live attenuated RNA viral vaccines. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Systematic annotation and analysis of "virmugens"-virulence factors whose mutants can be used as live attenuated vaccines.

    Science.gov (United States)

    Racz, Rebecca; Chung, Monica; Xiang, Zuoshuang; He, Yongqun

    2013-01-21

    Live attenuated vaccines are usually generated by mutation of genes encoding virulence factors. "Virmugen" is coined here to represent a gene that encodes for a virulent factor of a pathogen and has been proven feasible in animal models to make a live attenuated vaccine by knocking out this gene. Not all virulence factors are virmugens. VirmugenDB is a web-based virmugen database (http://www.violinet.org/virmugendb). Currently, VirmugenDB includes 225 virmugens that have been verified to be valuable for vaccine development against 57 bacterial, viral, and protozoan pathogens. Bioinformatics analysis has revealed significant patterns in virmugens. For example, 10 Gram-negative and 1 Gram-positive bacterial aroA genes are virmugens. A sequence analysis has revealed at least 50% of identities in the protein sequences of the 10 Gram-negative bacterial aroA virmugens. As a pathogen case study, Brucella virmugens were analyzed. Out of 15 verified Brucella virmugens, 6 are related to carbohydrate or nucleotide transport and metabolism, and 2 involving cell membrane biogenesis. In addition, 54 virmugens from 24 viruses and 12 virmugens from 4 parasites are also stored in VirmugenDB. Virmugens tend to involve metabolism of nutrients (e.g., amino acids, carbohydrates, and nucleotides) and cell membrane formation. Host genes whose expressions were regulated by virmugen mutation vaccines or wild type virulent pathogens have also been annotated and systematically compared. The bioinformatics annotation and analysis of virmugens helps to elucidate enriched virmugen profiles and the mechanisms of protective immunity, and further supports rational vaccine design.

  5. The administration of intranasal live attenuated influenza vaccine induces changes in the nasal microbiota and nasal epithelium gene expression profiles.

    Science.gov (United States)

    Tarabichi, Y; Li, K; Hu, S; Nguyen, C; Wang, X; Elashoff, D; Saira, K; Frank, Bryan; Bihan, Monika; Ghedin, E; Methé, Barbara A; Deng, Jane C

    2015-12-15

    Viral infections such as influenza have been shown to predispose hosts to increased colonization of the respiratory tract by pathogenic bacteria and secondary bacterial pneumonia. To examine how viral infections and host antiviral immune responses alter the upper respiratory microbiota, we analyzed nasal bacterial composition by 16S ribosomal RNA (rRNA) gene sequencing in healthy adults at baseline and at 1 to 2 weeks and 4 to 6 weeks following instillation of live attenuated influenza vaccine or intranasal sterile saline. A subset of these samples was submitted for microarray host gene expression profiling. We found that live attenuated influenza vaccination led to significant changes in microbial community structure, diversity, and core taxonomic membership as well as increases in the relative abundances of Staphylococcus and Bacteroides genera (both p < 0.05). Hypergeometric testing for the enrichment of gene ontology terms in the vaccinated group reflected a robust up-regulation of type I and type II interferon-stimulated genes in the vaccinated group relative to controls. Translational murine studies showed that poly I:C administration did in fact permit greater nasal Staphylococcus aureus persistence, a response absent in interferon alpha/beta receptor deficient mice. Collectively, our findings demonstrate that although the human nasal bacterial community is heterogeneous and typically individually robust, activation of a type I interferon (IFN)-mediated antiviral response may foster the disproportionate emergence of potentially pathogenic species such as S. aureus. This study was registered with Clinicaltrials.gov on 11/3/15, NCT02597647 .

  6. Enhanced expression of HIV and SIV vaccine antigens in the structural gene region of live attenuated rubella viral vectors and their incorporation into virions.

    Science.gov (United States)

    Virnik, Konstantin; Ni, Yisheng; Berkower, Ira

    2013-04-19

    Despite the urgent need for an HIV vaccine, its development has been hindered by virus variability, weak immunogenicity of conserved epitopes, and limited durability of the immune response. For other viruses, difficulties with immunogenicity were overcome by developing live attenuated vaccine strains. However, there is no reliable method of attenuation for HIV, and an attenuated strain would risk reversion to wild type. We have developed rubella viral vectors, based on the live attenuated vaccine strain RA27/3, which are capable of expressing important HIV and SIV vaccine antigens. The rubella vaccine strain has demonstrated safety, immunogenicity, and long lasting protection in millions of children. Rubella vectors combine the growth and immunogenicity of live rubella vaccine with the antigenicity of HIV or SIV inserts. This is the first report showing that live attenuated rubella vectors can stably express HIV and SIV vaccine antigens at an insertion site located within the structural gene region. Unlike the Not I site described previously, the new site accommodates a broader range of vaccine antigens without interfering with essential viral functions. In addition, antigens expressed at the structural site were controlled by the strong subgenomic promoter, resulting in higher levels and longer duration of antigen expression. The inserts were expressed as part of the structural polyprotein, processed to free antigen, and incorporated into rubella virions. The rubella vaccine strain readily infects rhesus macaques, and these animals will be the model of choice for testing vector growth in vivo and immunogenicity.

  7. Development of a Live Attenuated Bivalent Oral Vaccine Against Shigella sonnei Shigellosis and Typhoid Fever.

    Science.gov (United States)

    Wu, Yun; Chakravarty, Sumana; Li, Minglin; Wai, Tint T; Hoffman, Stephen L; Sim, B Kim Lee

    2017-01-15

    Shigella sonnei and Salmonella Typhi cause significant morbidity and mortality. We exploited the safety record of the oral, attenuated S. Typhi vaccine (Ty21a) by using it as a vector to develop a bivalent oral vaccine to protect against S. sonnei shigellosis and typhoid fever. We recombineered the S. sonnei form I O-antigen gene cluster into the Ty21a chromosome to create Ty21a-Ss, which stably expresses S. sonnei form I O antigen. To enhance survivability in the acid environment of the stomach, we created an acid-resistant strain, Ty21a-AR-Ss, by inserting Shigella glutaminase-glutamate decarboxylase systems coexpressed with S. sonnei form I O-antigen gene. Mice immunized intranasally with Ty21a-AR-Ss produced antibodies against S. sonnei and S. Typhi, and survived lethal intranasal S. sonnei challenge. This paves the way for proposed good manufacturing practices manufacture and clinical trials intended to test the clinical effectiveness of Ty21a-AR-Ss in protecting against S. sonnei shigellosis and typhoid fever, as compared with the current Ty21a vaccine. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  8. Development of a live, oral, attenuated vaccine against El Tor cholera.

    Science.gov (United States)

    Taylor, D N; Killeen, K P; Hack, D C; Kenner, J R; Coster, T S; Beattie, D T; Ezzell, J; Hyman, T; Trofa, A; Sjogren, M H

    1994-12-01

    Vibrio cholerae El Tor strains from Peru, Bangladesh, and Bahrain were attenuated by deletion of a genetic element that encodes virulence factors and RS1. The B subunit of ctx (ctxB) was reintroduced into the recA gene of the deletion mutants, rendering them unable to recombine with exogenous genetic elements and generating Peru-3, Bang-3, and Bah-3. Fifteen volunteers received one dose of various vaccine strains at 4 x 10(6) to 1 x 10(8) cfu. All strains colonized the gut. A > or = 4-fold rise in vibriocidal titer was observed in 14 volunteers, with titers of > or = 1600 in 13. Peru-3 was the least reactogenic, but 2 of 6 volunteers had loose stools. Peru-14, a filamentous motility-deficient mutant of Peru-3, was well tolerated and colonized 18 of 21 volunteers at doses of 2 x 10(6) to 1 x 10(9) cfu. Also, when 8 Peru-3 or Peru-5 vaccinees, 5 Peru-14 vaccinees, and 8 controls were challenged with 2 x 10(6) cfu V. cholerae El Tor Inaba (N16961), 11 vaccinees were protected compared with no controls. Peru-14 shows promise as a safe, effective, single-dose oral vaccine against El Tor cholera.

  9. Streptococcus iniae M-Like Protein Contributes to Virulence in Fish and Is a Target for Live Attenuated Vaccine Development

    Science.gov (United States)

    Locke, Jeffrey B.; Aziz, Ramy K.; Vicknair, Mike R.; Nizet, Victor; Buchanan, John T.

    2008-01-01

    Background Streptococcus iniae is a significant pathogen in finfish aquaculture, though knowledge of virulence determinants is lacking. Through pyrosequencing of the S. iniae genome we have identified two gene homologues to classical surface-anchored streptococcal virulence factors: M-like protein (simA) and C5a peptidase (scpI). Methodology/Principal Findings S. iniae possesses a Mga-like locus containing simA and a divergently transcribed putative mga-like regulatory gene, mgx. In contrast to the Mga locus of group A Streptococcus (GAS, S. pyogenes), scpI is located distally in the chromosome. Comparative sequence analysis of the Mgx locus revealed only one significant variant, a strain with an insertion frameshift mutation in simA and a deletion mutation in a region downstream of mgx, generating an ORF which may encode a second putative mga-like gene, mgx2. Allelic exchange mutagenesis of simA and scpI was employed to investigate the potential role of these genes in S. iniae virulence. Our hybrid striped bass (HSB) and zebrafish models of infection revealed that M-like protein contributes significantly to S. iniae pathogenesis whereas C5a peptidase-like protein does not. Further, in vitro cell-based analyses indicate that SiMA, like other M family proteins, contributes to cellular adherence and invasion and provides resistance to phagocytic killing. Attenuation in our virulence models was also observed in the S. iniae isolate possessing a natural simA mutation. Vaccination of HSB with the ΔsimA mutant provided 100% protection against subsequent challenge with a lethal dose of wild-type (WT) S. iniae after 1,400 degree days, and shows promise as a target for live attenuated vaccine development. Conclusions/Significance Analysis of M-like protein and C5a peptidase through allelic replacement revealed that M-like protein plays a significant role in S. iniae virulence, and the Mga-like locus, which may regulate expression of this gene, has an unusual arrangement

  10. Streptococcus iniae M-like protein contributes to virulence in fish and is a target for live attenuated vaccine development.

    Directory of Open Access Journals (Sweden)

    Jeffrey B Locke

    Full Text Available BACKGROUND: Streptococcus iniae is a significant pathogen in finfish aquaculture, though knowledge of virulence determinants is lacking. Through pyrosequencing of the S. iniae genome we have identified two gene homologues to classical surface-anchored streptococcal virulence factors: M-like protein (simA and C5a peptidase (scpI. METHODOLOGY/PRINCIPAL FINDINGS: S. iniae possesses a Mga-like locus containing simA and a divergently transcribed putative mga-like regulatory gene, mgx. In contrast to the Mga locus of group A Streptococcus (GAS, S. pyogenes, scpI is located distally in the chromosome. Comparative sequence analysis of the Mgx locus revealed only one significant variant, a strain with an insertion frameshift mutation in simA and a deletion mutation in a region downstream of mgx, generating an ORF which may encode a second putative mga-like gene, mgx2. Allelic exchange mutagenesis of simA and scpI was employed to investigate the potential role of these genes in S. iniae virulence. Our hybrid striped bass (HSB and zebrafish models of infection revealed that M-like protein contributes significantly to S. iniae pathogenesis whereas C5a peptidase-like protein does not. Further, in vitro cell-based analyses indicate that SiMA, like other M family proteins, contributes to cellular adherence and invasion and provides resistance to phagocytic killing. Attenuation in our virulence models was also observed in the S. iniae isolate possessing a natural simA mutation. Vaccination of HSB with the Delta simA mutant provided 100% protection against subsequent challenge with a lethal dose of wild-type (WT S. iniae after 1,400 degree days, and shows promise as a target for live attenuated vaccine development. CONCLUSIONS/SIGNIFICANCE: Analysis of M-like protein and C5a peptidase through allelic replacement revealed that M-like protein plays a significant role in S. iniae virulence, and the Mga-like locus, which may regulate expression of this gene, has an

  11. Development of a human live attenuated West Nile infectious DNA vaccine: Suitability of attenuating mutations found in SA14-14-2 for WN vaccine design.

    Science.gov (United States)

    Yamshchikov, Vladimir; Manuvakhova, Marina; Rodriguez, Efrain

    2016-01-01

    Direct attenuation of West Nile (WN) virus strain NY99 for the purpose of vaccine development is not feasible due to its high virulence and pathogenicity. Instead, we created highly attenuated chimeric virus W1806 with the serological identity of NY99. To further attenuate W1806, we investigated effects of mutations found in Japanese encephalitis virus vaccine SA14-14-2. WN viruses carrying all attenuating mutations lost infectivity in mammalian, but not in mosquito cells. No single reversion restored infectivity in mammalian cells, although increased infectivity in mosquito cells was observed. To identify a subset of mutations suitable for further attenuation of W1806, we analyzed effects of E138K and K279M changes on virulence, growth properties, and immunogenicity of derivatized W956, from which chimeric W1806 inherited its biological properties and attenuation profile. Despite strong dominant attenuating effect, introduction of only two mutations was not sufficient for attenuating W1806 to the safety level acceptable for human use.

  12. Long-term safety assessment of live attenuated tetravalent dengue vaccines: deliberations from a WHO technical consultation.

    Science.gov (United States)

    Bentsi-Enchill, Adwoa D; Schmitz, Julia; Edelman, Robert; Durbin, Anna; Roehrig, John T; Smith, Peter G; Hombach, Joachim; Farrar, Jeremy

    2013-05-28

    Dengue is a rapidly growing public health threat with approximately 2.5 billion people estimated to be at risk. Several vaccine candidates are at various stages of pre-clinical and clinical development. Thus far, live dengue vaccine candidates have been administered to several thousands of volunteers and were well-tolerated, with minimal short-term safety effects reported in Phase I and Phase II clinical trials. Based on the natural history of dengue, a theoretical possibility of an increased risk of severe dengue as a consequence of vaccination has been hypothesized but not yet observed. In October 2011, the World Health Organization (WHO) convened a consultation of experts in dengue, vaccine regulation and vaccine safety to review the current scientific evidence regarding safety concerns associated with live attenuated dengue vaccines and, in particular, to consider methodological approaches for their long-term evaluation. In this paper we summarize the scientific background and methodological considerations relevant to the safety assessment of these vaccines. Careful planning and a coordinated approach to safety assessment are recommended to ensure adequate long-term evaluation of dengue vaccines that will support their introduction and continued use.

  13. Revaccination of Guinea Pigs With the Live Attenuated Mycobacterium tuberculosis Vaccine MTBVAC Improves BCG's Protection Against Tuberculosis.

    Science.gov (United States)

    Clark, Simon; Lanni, Faye; Marinova, Dessislava; Rayner, Emma; Martin, Carlos; Williams, Ann

    2017-09-01

    The need for an effective vaccine against human tuberculosis has driven the development of different candidates and vaccination strategies. Novel live attenuated vaccines are being developed that promise greater safety and efficacy than BCG against tuberculosis. We combined BCG with the vaccine MTBVAC to evaluate whether the efficacy of either vaccine would be affected upon revaccination. In a well-established guinea pig model of aerosol infection with Mycobacterium tuberculosis, BCG and MTBVAC delivered via various prime-boost combinations or alone were compared. Efficacy was determined by a reduction in bacterial load 4 weeks after challenge. Efficacy data suggests MTBVAC-associated immunity is longer lasting than that of BCG when given as a single dose. Long and short intervals between BCG prime and MTBVAC boost resulted in improved efficacy in lungs, compared with BCG given alone. A shorter interval between MTBVAC prime and BCG boost resulted in improved efficacy in lungs, compared with BCG given alone. A longer interval resulted in protection equivalent to that of BCG given alone. These data indicate that, rather than boosting the waning efficacy of BCG, a vaccination schedule involving a combination of the 2 vaccines yielded stronger immunity to M. tuberculosis infection. This work supports development of MTBVAC use as a revaccination strategy to improve on the effects of BCG in vaccinated people living in tuberculosis-endemic countries.

  14. Pathology resulting from the administration of a live attenuated anti-Schistosoma haematobium vaccine in baboons.

    Science.gov (United States)

    Byram, J E; Harrison, R A; von Lichtenberg, F; Webbe, G; Sturrock, R F

    1989-01-01

    Baboons (Papio anubis) were injected in the leg muscle with 18,000 20 Krad irradiated schistosomula of Schistosoma haematobium. Four protocols were followed: single, primary injection; single injection into animals primed by patent S. haematobium infection; secondary vaccine injection following an earlier injection; and single injection following praziquantel treatment of infected animals. Injection of the putative vaccine elicited localized mixed inflammatory infiltration at the site of injection which was both intense and prolonged. Three grades of tissue reaction were seen: the relatively mild primary response; the response in infected animals which had enhanced tissue eosinophilia; and the response in animals primed by prior injection and drug-treated prior infection. The latter 2 showed intensification of eosinophilia, stellate abscesses in the lesion centers, and perischistosomular Hoeppli precipitates. Intramuscular lesions peaked at 14 days for the primary response and at 7 days for all secondary responses. Traces of the milder lesions persisted beyond 4 weeks; more severe reactions healed more rapidly. Some schistosomula survived for 14 days in the milder reactions. A few larvae were deposited in the skin by backflushing of the injectate which produced local inflammation. Compared to mice, live schistosome vaccines injected into baboons elicited greater local inflammation; however, while evidence suggested that sporadic vaccine schistosomula did reach the lymphatic nodes draining the injection sites, no systemic lesions were found and the injection sites healed in approximately 5-6 weeks without permanent damage.

  15. A Phase II, Randomized, Safety and Immunogenicity Trial of a Re-Derived, Live-Attenuated Dengue Virus Vaccine in Healthy Children and Adults Living in Puerto Rico

    Science.gov (United States)

    Bauer, Kristen; Esquilin, Ines O.; Cornier, Alberto Santiago; Thomas, Stephen J.; Quintero del Rio, Ana I.; Bertran-Pasarell, Jorge; Morales Ramirez, Javier O.; Diaz, Clemente; Carlo, Simon; Eckels, Kenneth H.; Tournay, Elodie; Toussaint, Jean-Francois; De La Barrera, Rafael; Fernandez, Stefan; Lyons, Arthur; Sun, Wellington; Innis, Bruce L.

    2015-01-01

    This was a double-blind, randomized, controlled, phase II clinical trial, two dose study of re-derived, live-attenuated, tetravalent dengue virus (TDEN) vaccine (two formulations) or placebo in subjects 1–50 years of age. Among the 636 subjects enrolled, 331 (52%) were primed, that is, baseline seropositive to at least one dengue virus (DENV) type. Baseline seropositivity prevalence increased with age (10% [< 2 years], 26% [2–4 years], 60% [5–20 years], and 93% [21–50 years]). Safety profiles of TDEN vaccines were similar to placebo regardless of priming status. No vaccine-related serious adverse events (SAEs) were reported. Among unprimed subjects, immunogenicity (geometric mean antibody titers [GMT] and seropositivity rates) for each DENV increased substantially in both TDEN vaccine groups with at least 74.6% seropositive for four DENV types. The TDEN vaccine candidate showed an acceptable safety and immunogenicity profile in children and adults ranging from 1 to 50 years of age, regardless of priming status. ClinicalTrials.gov: NCT00468858. PMID:26175027

  16. Safety and immunogenicity of a rederived, live-attenuated dengue virus vaccine in healthy adults living in Thailand: a randomized trial.

    Science.gov (United States)

    Watanaveeradej, Veerachai; Gibbons, Robert V; Simasathien, Sriluck; Nisalak, Ananda; Jarman, Richard G; Kerdpanich, Angkool; Tournay, Elodie; De La Barrerra, Rafael; Dessy, Francis; Toussaint, Jean-François; Eckels, Kenneth H; Thomas, Stephen J; Innis, Bruce L

    2014-07-01

    Safety and immunogenicity of two formulations of a live-attenuated tetravalent dengue virus (TDEN) vaccine produced using rederived master seeds from a precursor vaccine were tested against a placebo control in a phase II, randomized, double blind trial (NCT00370682). Two doses were administered 6 months apart to 120 healthy, predominantly flavivirus-primed adults (87.5% and 97.5% in the two vaccine groups and 92.5% in the placebo group). Symptoms and signs reported after vaccination were mild to moderate and transient. There were no vaccine-related serious adverse events or dengue cases reported. Asymptomatic, low-level viremia (dengue virus type 2 [DENV-2], DENV-3, or DENV-4) was detected in 5 of 80 vaccine recipients. One placebo recipient developed a subclinical natural DENV-1 infection. All flavivirus-unprimed subjects and at least 97.1% of flavivirus-primed subjects were seropositive to antibodies against all four DENV types 1 and 3 months post-TDEN dose 2. The TDEN vaccine was immunogenic with an acceptable safety profile in flavivirus-primed adults.

  17. Live, attenuated influenza A H5N1 candidate vaccines provide broad cross-protection in mice and ferrets.

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    Amorsolo L Suguitan

    2006-09-01

    Full Text Available BACKGROUND: Recent outbreaks of highly pathogenic influenza A H5N1 viruses in humans and avian species that began in Asia and have spread to other continents underscore an urgent need to develop vaccines that would protect the human population in the event of a pandemic. METHODS AND FINDINGS: Live, attenuated candidate vaccines possessing genes encoding a modified H5 hemagglutinin (HA and a wild-type (wt N1 neuraminidase from influenza A H5N1 viruses isolated in Hong Kong and Vietnam in 1997, 2003, and 2004, and remaining gene segments derived from the cold-adapted (ca influenza A vaccine donor strain, influenza A/Ann Arbor/6/60 ca (H2N2, were generated by reverse genetics. The H5N1 ca vaccine viruses required trypsin for efficient growth in vitro, as predicted by the modification engineered in the gene encoding the HA, and possessed the temperature-sensitive and attenuation phenotypes specified by the internal protein genes of the ca vaccine donor strain. More importantly, the candidate vaccines were immunogenic in mice. Four weeks after receiving a single dose of 10(6 50% tissue culture infectious doses of intranasally administered vaccines, mice were fully protected from lethality following challenge with homologous and antigenically distinct heterologous wt H5N1 viruses from different genetic sublineages (clades 1, 2, and 3 that were isolated in Asia between 1997 and 2005. Four weeks after receiving two doses of the vaccines, mice and ferrets were fully protected against pulmonary replication of homologous and heterologous wt H5N1 viruses. CONCLUSIONS: The promising findings in these preclinical studies of safety, immunogenicity, and efficacy of the H5N1 ca vaccines against antigenically diverse H5N1 vaccines provide support for their careful evaluation in Phase 1 clinical trials in humans.

  18. Generation and characterization of a cold-adapted attenuated live H3N2 subtype influenza virus vaccine candidate

    Institute of Scientific and Technical Information of China (English)

    AN Wen-qi; LIU Xiu-fan; WANG Xi-liang; YANG Peng-hui; DUAN Yue-qiang; LUO De-yan; TANG Chong; JIA Wei-hong; XING Li; SHI Xin-fu; ZHANG Yu-jing

    2009-01-01

    Background H3N2 subtype influenza A viruses have been identified in humans worldwide, raising concerns about their pandemic potential and prompting the development of candidate vaccines to protect humans against this subtype of influenza A virus. The aim of this study was to establish a system for rescuing of a cold-adapted high-yielding H3N2 subtype human influenza virus by reverse genetics. Methods In order to generate better and safer vaccine candidate viruses, a cold-adapted high yielding reassortant H3N2 influenza A virus was genetically constructed by reverse genetics and was designated as rgAA-H3N2. The rgAA-H3N2 virus contained HA and NA genes from an epidemic strain A/Wisconsin/67/2005 (H3N2) in a background of internal genes derived from the master donor viruses (MDV), cold-adapted (ca), temperature sensitive (te), live attenuated influenza virus strain A/Ann Arbor/6/60 (MDV-A). Results In this presentation, the virus HA titer of rgAA-H3N2 in the allantoic fluid from infected embryonated eggs was as high as 1:1024. A fluorescent focus assay (FFU) was performed 24-36 hours post-infection using a specific antibody and bright staining was used for determining the virus titer. The allantoic fluid containing the recovered influenza virus was analyzed in a hemagglutination inhibition (HI) test and the specific inhibition was found. Conclusion The results mentioned above demonstrated that cold-adapted, attenuated reassortant H3N2 subtype influenza A virus was successfully generated, which laid a good foundation for the further related research.

  19. Early biodistribution and persistence of a protective live attenuated SIV vaccine elicits localised innate responses in multiple lymphoid tissues.

    Directory of Open Access Journals (Sweden)

    Deborah Ferguson

    Full Text Available Vaccination of Mauritian cynomolgus macaques with the attenuated nef-truncated C8 variant of SIVmac251/32H (SIVmacC8 induces early, potent protection against pathogenic, heterologous challenge before the maturation of cognate immunity. To identify processes that contribute to early protection in this model the pathogenesis, anatomical distribution and viral vaccine kinetics were determined in relation to localised innate responses triggered by vaccination. The early biodistribution of SIVmacC8 was defined by rapid, widespread dissemination amongst multiple lymphoid tissues, detectable after 3 days. Cell-associated viral RNA dynamics identified mesenteric lymph nodes (MLN and spleen, as well as the gut mucosae, as early major contributors of systemic virus burden. Rapid, localised infection was populated by discrete foci of persisting virus-infected cells. Localised productive infection triggered a broad innate response, with type-1 interferon sensitive IRF-7, STAT-1, TRIM5α and ApoBEC3G genes all upregulated during the acute phase but induction did not prevent viral persistence. Profound changes in vaccine-induced cell-surface markers of immune activation were detected on macrophages, B-cells and dendritic cells (DC-SIGN, S-100, CD40, CD11c, CD123 and CD86. Notably, high DC-SIGN and S100 staining for follicular and interdigitating DCs respectively, in MLN and spleen were detected by 3 days, persisting 20 weeks post-vaccination. Although not formally evaluated, the early biodistribution of SIVmacC8 simultaneously targets multiple lymphoid tissues to induce strong innate immune responses coincident at the same sites critical for early protection from wild-type viruses. HIV vaccines which stimulate appropriate innate, as well as adaptive responses, akin to those generated by live attenuated SIV vaccines, may prove the most efficacious.

  20. Evaluation of eight live attenuated vaccine candidates for protection against challenge with virulent Mycobacterium avium subspecies paratuberculosis in mice

    Directory of Open Access Journals (Sweden)

    John P Bannantine

    2014-07-01

    Full Text Available Johne’s disease is caused by Mycobacterium avium subsp. paratuberculosis (MAP, which results in serious economic losses worldwide in farmed livestock such as cattle, sheep and goats. To control this disease, an effective vaccine with minimal adverse effects is needed. In order to identify a live vaccine for Johne’s disease, we evaluated eight attenuated mutant strains of MAP using a C57BL/6 mouse model. The persistence of the vaccine candidates was measured at 6, 12, and 18 weeks post vaccination. Only strains 320, 321 and 329 colonized both the liver and spleens up until the 12-week time point. The remaining five mutants showed no survival in those tissues, indicating their complete attenuation in the mouse model. The candidate vaccine strains demonstrated different levels of protection based on colonization of the challenge strain in liver and spleen tissues at 12 and 18 weeks post vaccination. Based on total MAP burden in both tissues at both time points, strain 315 (MAP1566::Tn5370 was the most protective whereas strain 318 (intergenic Tn5367 insertion between MAP0282c and MAP0283c had the most colonization. Mice vaccinated with an undiluted commercial vaccine preparation displayed the highest bacterial burden as well as enlarged spleens indicative of a strong infection. Selected vaccine strains that showed promise in the mouse model were moved forward into a goat challenge model. The results suggest that the mouse trial, as conducted, may have a relatively poor predictive value for protection in a ruminant host such as goats.

  1. Heterotypic Dengue Infection with Live Attenuated Monotypic Dengue Virus Vaccines: Implications for Vaccination of Populations in Areas Where Dengue Is Endemic

    OpenAIRE

    Anna P Durbin; Schmidt, Alexander; Elwood, Dan; Wanionek, Kimberli A.; Lovchik, Janece; Thumar, Bhavin; Murphy, Brian R.; Whitehead, Stephen S.

    2011-01-01

    Background. Because infection with any of the 4 Dengue virus serotypes may elicit both protective neutralizing antibodies and nonneutralizing antibodies capable of enhancing subsequent heterotypic Dengue virus infections, the greatest risk for severe dengue occurs during a second, heterotypic Dengue virus infection. It remains unclear whether the replication of live attenuated vaccine viruses will be similarly enhanced when administered to Dengue-immune individuals.

  2. Construction and evaluation of V. cholerae O139 mutant, VCUSM21P, as a safe live attenuated cholera vaccine.

    Science.gov (United States)

    Murugaiah, Chandrika; Nik Mohd Noor, Nik Zuraina; Mustafa, Shyamoli; Manickam, Ravichandran; Pattabhiraman, Lalitha

    2014-01-01

    Cholera is a major infectious disease, affecting millions of lives annually. In endemic areas, implementation of vaccination strategy against cholera is vital. As the use of safer live vaccine that can induce protective immunity against Vibrio cholerae O139 infection is a promising approach for immunization, we have designed VCUSM21P, an oral cholera vaccine candidate, which has ctxA that encodes A subunit of ctx and mutated rtxA/C, ace and zot mutations. VCUSM21P was found not to disassemble the actin of HEp2 cells. It colonized the mice intestine approximately 1 log lower than that of the Wild Type (WT) strain obtained from Hospital Universiti Sains Malaysia. In the ileal loop assay, unlike WT challenge, 1×10⁶ and 1×10⁸ colony forming unit (CFU) of VCUSM21P was not reactogenic in non-immunized rabbits. Whereas, the reactogenicity caused by the WT in rabbits immunized with 1×10¹⁰ CFU of VCUSM21P was found to be reduced as evidenced by absence of fluid in loops administered with 1×10²-1×10⁷ CFU of WT. Oral immunization using 1×10¹⁰ CFU of VCUSM21P induced both IgA and IgG against Cholera Toxin (CT) and O139 lipopolysaccharides (LPS). The serum vibriocidal antibody titer had a peak rise of 2560 fold on week 4. Following Removable Intestinal Tie Adult Rabbit Diarrhoea (RITARD) experiment, the non-immunized rabbits were found not to be protected against lethal challenge with 1×10⁹ CFU WT, but 100% of immunized rabbits survived the challenge. In the past eleven years, V. cholerae O139 induced cholera has not been observed. However, attenuated VCUSM21P vaccine could be used for vaccination program against potentially fatal endemic or emerging cholera caused by V. cholerae O139.

  3. Gene deleted live attenuated Leishmania vaccine candidates against visceral leishmaniasis elicit pro-inflammatory cytokines response in human PBMCs

    Science.gov (United States)

    Avishek, Kumar; Kaushal, Himanshu; Gannavaram, Sreenivas; Dey, Ranadhir; Selvapandiyan, Angamuthu; Ramesh, V.; Negi, Narender Singh; Dubey, Uma S.; Nakhasi, Hira L.; Salotra, Poonam

    2016-01-01

    Currently no effective vaccine is available for human visceral leishmaniasis(VL) caused by Leishmania donovani. Previously, we showed that centrin1 and p27gene deleted live attenuated Leishmania parasites (LdCen1−/− and Ldp27−/−) are safe, immunogenic and protective in animal models. Here, to assess the correlates of protection, we evaluated immune responses induced by LdCen1−/− and Ldp27−/− in human blood samples obtained from healthy, healed VL (HVL), post kala-azar dermal leishmaniasis(PKDL) and VL subjects. Both parasites infected human macrophages, as effectively as the wild type parasites. Further, LdCen1−/− and Ldp27−/− strongly stimulated production of pro-inflammatory cytokines including, IL-12, IFN-γ, TNF-α, IL-2, IL-6 and IL-17 in the PBMCs obtained from individuals with a prior exposure to Leishmania (HVL and PKDL). There was no significant stimulation of anti-inflammatory cytokines (IL-4 and IL-10). Induction of Th1 biased immune responses was supported by a remarkable increase in IFN-γ secreting CD4+ and CD8+ T cells and IL-17 secreting CD4+ cells in PBMCs from HVL cases with no increase in IL-10 secreting T cells. Hence, LdCen1−/− and Ldp27−/− are promising as live vaccine candidates against VL since they elicit strong protective immune response in human PBMCs from HVL, similar to the wild type parasite infection, mimicking a naturally acquired protection following cure. PMID:27624408

  4. Development of Clade-Specific and Broadly Reactive Live Attenuated Influenza Virus Vaccines against Rapidly Evolving H5 Subtype Viruses.

    Science.gov (United States)

    Boonnak, Kobporn; Matsuoka, Yumiko; Wang, Weijia; Suguitan, Amorsolo L; Chen, Zhongying; Paskel, Myeisha; Baz, Mariana; Moore, Ian; Jin, Hong; Subbarao, Kanta

    2017-08-01

    We have developed pandemic live attenuated influenza vaccines (pLAIVs) against clade 1 H5N1 viruses on an Ann Arbor cold-adapted (ca) backbone that induced long-term immune memory. In 2015, many human infections caused by a new clade (clade 2.2.1.1) of goose/Guangdong (gs/GD) lineage H5N1 viruses were reported in Egypt, which prompted updating of the H5N1 pLAIV. We explored two strategies to generate suitable pLAIVs. The first approach was to modify the hemagglutinin gene of a highly pathogenic wild-type (wt) clade 2.2.1.1 virus, A/Egypt/N03434/2009 (Egy/09) (H5N1), with its unmodified neuraminidase (NA) gene; this virus was designated Egy/09 ca The second approach was to select a low-pathogenicity avian influenza H5 virus that elicited antibodies that cross-reacted with a broad range of H5 viruses, including the Egypt H5N1 viruses, and contained a novel NA subtype for humans. We selected the low-pathogenicity A/duck/Hokkaido/69/2000 (H5N3) (dk/Hok/00) virus for this purpose. Both candidate vaccines were attenuated and immunogenic in ferrets, inducing antibodies that neutralized homologous and heterologous H5 viruses with different degrees of cross-reactivity; Egy/09 ca vaccine antisera were more specific for the gs/GD lineage viruses but did not neutralize recent North American isolates (clade 2.3.4.4), whereas antisera from dk/Hok/69 ca-vaccinated ferrets cross-reacted with clade 2.3.4.4 and 2.2.1 viruses but not clade 1 or 2.1 viruses. When vaccinated ferrets were challenged with homologous and heterologous H5 viruses, challenge virus replication was reduced in the respiratory tract. Thus, the two H5 pLAIV candidates are suitable for clinical development to protect humans from infection with different clades of H5 viruses.IMPORTANCE In response to the continuing evolution of H5N1 avian influenza viruses and human infections, new candidate H5 live attenuated vaccines were developed by using two different approaches: one targeted a specific circulating strain in

  5. Comparison of the trivalent live attenuated vs. inactivated influenza vaccines among U.S. military service members.

    Science.gov (United States)

    Eick, Angelia A; Wang, Zhong; Hughes, Hayley; Ford, Stephen M; Tobler, Steven K

    2009-06-02

    Limited effectiveness data are available comparing live attenuated influenza vaccine (LAIV) to inactivated influenza vaccine (TIV) among adults. To compare the incidence of influenza-like illness following immunization of adults with LAIV vs. TIV, we conducted a retrospective cohort analysis of active component U.S. military personnel for the 2005-2006 and 2006-2007 influenza seasons. Recruits experienced a much higher burden of disease compared to non-recruits, with crude incidence rates of influenza-like illness 2-16 times higher than non-recruits depending on the season and cohort. For both seasons, a slightly greater protection from influenza-like illness was found for non-recruits who received TIV compared to LAIV (adjusted incidence rate ratio, 1.17 (95% CI, 1.14-1.20) and 1.33 (95% CI, 1.30-1.36), 2005-2006 and 2006-2007 influenza seasons, respectively). However, for Army and Air Force recruits, LAIV was found to provide significantly greater protection from influenza-like illnesses compared to TIV, with adjusted incidence rates of influenza-like illness 22-51% and 18-47% lower among LAIV compared to TIV recipients for the 2005-2006 and 2006-2007 influenza seasons, respectively. Possible reasons for differences in recruit and non-recruit findings include differences in pre-existing influenza antibody levels, differing respiratory disease burden, and/or unmeasured confounding. Consideration of these findings should be made when developing influenza immunization policies.

  6. Recent advances in the study of live attenuated cell-cultured smallpox vaccine LC16m8.

    Science.gov (United States)

    Eto, Akiko; Saito, Tomoya; Yokote, Hiroyuki; Kurane, Ichiro; Kanatani, Yasuhiro

    2015-11-01

    LC16m8 is a live, attenuated, cell-cultured smallpox vaccine that was developed and licensed in Japan in the 1970s, but was not used in the campaign to eradicate smallpox. In the early 2000s, the potential threat of bioterrorism led to reconsideration of the need for a smallpox vaccine. Subsequently, LC16m8 production was restarted in Japan in 2002, requiring re-evaluation of its safety and efficacy. Approximately 50,000 children in the 1970s and about 3500 healthy adults in the 2000s were vaccinated with LC16m8 in Japan, and 153 adults have been vaccinated with LC16m8 or Dryvax in phase I/II clinical trials in the USA. These studies confirmed the safety and efficacy of LC16m8, while several studies in animal models have shown that LC16m8 protects the host against viral challenge. The World Health Organization Strategic Advisory Group of Experts on Immunization recommended LC16m8, together with ACAM2000, as a stockpile vaccine in 2013. In addition, LC16m8 is expected to be a viable alternative to first-generation smallpox vaccines to prevent human monkeypox.

  7. PRODUCTION OF HOMOLOGOUS LIVE ATTENUATED CELL CULTURE VACCINE FOR THE CONTROL OF PESTE DES PETITS RUMINANTS IN SMALL RUMINANTS

    Directory of Open Access Journals (Sweden)

    M. ASIM, A. RASHID, A. H. CHAUDHARY AND M. S. NOOR

    2009-05-01

    Full Text Available Antibody response of a live-attenuated Peste des Petits Ruminants (PPR cell culture vaccine was studied at Veterinary Research Institute, Lahore, Pakistan. For this purpose, one group of five sheep and 5 goats each was vaccinated subcutaneously with 1 ml reconstituted PPR vaccine and second group of five sheep and 5 goats was inoculated with 1 ml saline solution. Blood samples were collected before and after vaccination, sera were obtained and analyzed for antibodies against PPR by competitive ELISA (cELISA. Findings suggested that antibody titres at day zero, 21 and 45 were 24.762 ± 2.69, 65.467 ± 2.29 and 83.012 ± 2.11 in sheep and 18.723 ± 2.27, 59.162 ± 1.53 and 72.176 ± 2.93 in goats, respectively. No untoward reactions were observed following vaccination. All vaccinated animals developed high titre of antibodies (PI>50.

  8. Genetic variations of live attenuated plague vaccine strains (Yersinia pestis EV76 lineage) during laboratory passages in different countries.

    Science.gov (United States)

    Cui, Yujun; Yang, Xianwei; Xiao, Xiao; Anisimov, Andrey P; Li, Dongfang; Yan, Yanfeng; Zhou, Dongsheng; Rajerison, Minoarisoa; Carniel, Elisabeth; Achtman, Mark; Yang, Ruifu; Song, Yajun

    2014-08-01

    Plague, one of the most devastating infectious diseases in human history, is caused by the bacterial species Yersinia pestis. A live attenuated Y. pestis strain (EV76) has been widely used as a plague vaccine in various countries around the world. Here we compared the whole genome sequence of an EV76 strain used in China (EV76-CN) with the genomes of Y. pestis wild isolates to identify genetic variations specific to the EV76 lineage. We identified 6 SNPs and 6 Indels (insertions and deletions) differentiating EV76-CN from its counterparts. Then, we screened these polymorphic sites in 28 other strains of EV76 lineage that were stored in different countries. Based on the profiles of SNPs and Indels, we reconstructed the parsimonious dissemination history of EV76 lineage. This analysis revealed that there have been at least three independent imports of EV76 strains into China. Additionally, we observed that the pyrE gene is a mutation hotspot in EV76 lineages. The fine comparison results based on whole genome sequence in this study provide better understanding of the effects of laboratory passages on the accumulation of genetic polymorphisms in plague vaccine strains. These variations identified here will also be helpful in discriminating different EV76 derivatives. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. Successful cross-protective efficacy induced by heat-adapted live attenuated nephropathogenic infectious bronchitis virus derived from a natural recombinant strain.

    Science.gov (United States)

    Lim, Tae-Hyun; Youn, Ha-Na; Yuk, Seong-Su; Kwon, Jung-Hoon; Hong, Woo-Tack; Gwon, Gyeong-Bin; Lee, Jung-Ah; Lee, Joong-Bok; Lee, Sang-Won; Song, Chang-Seon

    2015-12-16

    A natural recombinant nephropathogenic K40/09 strain of infectious bronchitis virus (IBV) was heat-adapted for possible future use as live attenuated vaccine. The K40/09 strain was selected during successive serial passages in specific-pathogen free (SPF) embryonated eggs at sub-optimal higher temperature (56°C). Unlike the parental strain, the attenuated strain, designated K40/09 HP50, was found to be safe in 1-day-old SPF chicks, which showed neither mortality nor signs of morbidity, and rarely induced ciliostasis or histological changes in the trachea and kidney after intraocular and fine-spray administration. K40/09 HP50 provided almost complete protection against two distinct subgroups of a nephropathogenic strain (KM91-like and QX-like subgroup) and elicited the production of high titers of neutralizing antibody (neutralization index of 3.6). We conclude that the K40/09 HP50 vaccine virus is rapidly attenuated by heat adaptation and exhibits the desired level of attenuation, immunogenicity, and protective efficacy required for a live attenuated vaccine. These results indicate that the K40/09 vaccine could be helpful for the reduction of economic losses caused by recently emergent nephropathogenic IBV infection in many countries.

  10. MMR (measles, mumps, and rubella) vaccine - what you need to know

    Science.gov (United States)

    ... taken in its entirety from the CDC MMR (Measles, Mumps, & Rubella) Vaccine Information Statement (VIS): www.cdc. ... Why get vaccinated? Measles, mumps, and rubella are serious ... common, especially among children. Measles Measles virus causes ...

  11. Mumps vaccine effectiveness in primary schools and households, the Netherlands, 2008

    NARCIS (Netherlands)

    Snijders, B.E.; Lier, A. van; Kassteele, J. van de; Fanoy, E.B.; Ruijs, W.L.M.; Hulshof, F.; Blauwhof, A.; Schipper, M.; Binnendijk, R. van; Boot, H.J.; Melker, H.E. de; Hahne, S.J.

    2012-01-01

    To estimate the mumps vaccine effectiveness (VE) during a large genotype D mumps outbreak, we conducted a cross-sectional study in eight primary schools and associated households in the Netherlands. Questionnaires were used to collect information on the occurrence of mumps. Multivariate analyses wer

  12. Early Transcriptional Signatures of the Immune Response to a Live Attenuated Tetravalent Dengue Vaccine Candidate in Non-human Primates

    Science.gov (United States)

    Strouts, Fiona R.; Popper, Stephen J.; Partidos, Charalambos D.; Stinchcomb, Dan T.; Osorio, Jorge E.; Relman, David A.

    2016-01-01

    Background The development of a vaccine against dengue faces unique challenges, including the complexity of the immune responses to the four antigenically distinct serotypes. Genome-wide transcriptional profiling provides insight into the pathways and molecular features that underlie responses to immune system stimulation, and may facilitate predictions of immune protection. Methodology/Principal Findings In this study, we measured early transcriptional responses in the peripheral blood of cynomolgus macaques following vaccination with a live, attenuated tetravalent dengue vaccine candidate, TDV, which is based on a DENV-2 backbone. Different doses and routes of vaccine administration were used, and viral load and neutralizing antibody titers were measured at different time-points following vaccination. All 30 vaccinated animals developed a neutralizing antibody response to each of the four dengue serotypes, and only 3 of these animals had detectable serum viral RNA after challenge with wild-type dengue virus (DENV), suggesting protection of vaccinated animals to DENV infection. The vaccine induced statistically significant changes in 595 gene transcripts on days 1, 3, 5 and 7 as compared with baseline and placebo-treated animals. Genes involved in the type I interferon (IFN) response, including IFI44, DDX58, MX1 and OASL, exhibited the highest fold-change in transcript abundance, and this response was strongest following double dose and subcutaneous (versus intradermal) vaccine administration. In addition, modules of genes involved in antigen presentation, dendritic cell activation, and T cell activation and signaling were enriched following vaccination. Increased abundance of gene transcripts related to T cell activation on day 5, and the type I IFN response on day 7, were significantly correlated with the development of high neutralizing antibody titers on day 30. Conclusions/Significance These results suggest that early transcriptional responses may be

  13. Effect of broccoli sprouts on nasal response to live attenuated influenza virus in smokers: a randomized, double-blind study.

    Directory of Open Access Journals (Sweden)

    Terry L Noah

    Full Text Available Smokers have increased susceptibility and altered innate host defense responses to influenza virus infection. Broccoli sprouts are a source of the Nrf2 activating agentsulforaphane, and short term ingestion of broccoli sprout homogenates (BSH has been shown to reduce nasal inflammatory responses to oxidant pollutants.Assess the effects of BSH on nasal cytokines, virus replication, and Nrf2-dependent enzyme expression in smokers and nonsmokers.We conducted a randomized, double-blind, placebo-controlled trial comparing the effects of BSH on serially sampled nasal lavage fluid (NLF cytokines, viral sequence quantity, and Nrf2-dependent enzyme expression in NLF cells and biopsied epithelium. Healthy young adult smokers and nonsmokers ingested BSH or placebo (alfalfa sprout homogenate for 4 days, designated Days -1, 0, 1, 2. On Day 0 they received standard vaccine dose of live attenuated influenza virus (LAIV intranasally. Nasal lavage fluids and nasal biopsies were collected serially to assess response to LAIV.In area under curve analyses, post-LAIV IL-6 responses (P = 0.03 and influenza sequences (P = 0.01 were significantly reduced in NLF from BSH-treated smokers, whilequinoneoxidoreductasein NLF cells was significantly increased. In nonsmokers, a similar trend for reduction in virus quantity with BSH did not reach statistical significance.In smokers, short term ingestion of broccoli sprout homogenates appears to significantly reduce some virus-induced markers of inflammation, as well as reducing virus quantity. Nutritional antioxidant interventions have promise as a safe, low-cost strategy for reducing influenza risk among smokers and other at risk populations.ClinicalTrials.gov NCT01269723.

  14. Haloarchaeal gas vesicle nanoparticles displaying Salmonella SopB antigen reduce bacterial burden when administered with live attenuated bacteria.

    Science.gov (United States)

    DasSarma, Priya; Negi, Vidya Devi; Balakrishnan, Arjun; Karan, Ram; Barnes, Susan; Ekulona, Folasade; Chakravortty, Dipshikha; DasSarma, Shiladitya

    2014-07-31

    Innovative vaccines against typhoid and other Salmonella diseases that are safe, effective, and inexpensive are urgently needed. In order to address this need, buoyant, self-adjuvating gas vesicle nanoparticles (GVNPs) from the halophilic archaeon Halobacterium sp. NRC-1 were bioengineered to display the highly conserved Salmonella enterica antigen SopB, a secreted inosine phosphate effector protein injected by pathogenic bacteria during infection into the host cell. Two highly conserved sopB gene segments near the 3'-coding region, named sopB4 and B5, were each fused to the gvpC gene, and resulting GVNPs were purified by centrifugally accelerated flotation. Display of SopB4 and B5 antigenic epitopes on GVNPs was established by Western blotting analysis using antisera raised against short synthetic peptides of SopB. Immunostimulatory activities of the SopB4 and B5 nanoparticles were tested by intraperitoneal administration of recombinant GVNPs to BALB/c mice which had been immunized with S. enterica serovar Typhimurium 14028 ΔpmrG-HM-D (DV-STM-07), a live attenuated vaccine strain. Proinflammatory cytokines IFN-γ, IL-2, and IL-9 were significantly induced in mice boosted with SopB5-GVNPs, consistent with a robust Th1 response. After challenge with virulent S. enterica serovar Typhimurium 14028, bacterial burden was found to be diminished in spleen of mice boosted with SopB4-GVNPs and absent or significantly diminished in liver, mesenteric lymph node, and spleen of mice boosted with SopB5-GVNPs, indicating that the C-terminal portions of SopB displayed on GVNPs elicit a protective response to Salmonella infection in mice. SopB antigen-GVNPs were found to be stable at elevated temperatures for extended periods without refrigeration in Halobacterium cells. The results all together show that bioengineered GVNPs are likely to represent a valuable platform for the development of improved vaccines against Salmonella diseases.

  15. Early Transcriptional Signatures of the Immune Response to a Live Attenuated Tetravalent Dengue Vaccine Candidate in Non-human Primates.

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    Fiona R Strouts

    2016-05-01

    Full Text Available The development of a vaccine against dengue faces unique challenges, including the complexity of the immune responses to the four antigenically distinct serotypes. Genome-wide transcriptional profiling provides insight into the pathways and molecular features that underlie responses to immune system stimulation, and may facilitate predictions of immune protection.In this study, we measured early transcriptional responses in the peripheral blood of cynomolgus macaques following vaccination with a live, attenuated tetravalent dengue vaccine candidate, TDV, which is based on a DENV-2 backbone. Different doses and routes of vaccine administration were used, and viral load and neutralizing antibody titers were measured at different time-points following vaccination. All 30 vaccinated animals developed a neutralizing antibody response to each of the four dengue serotypes, and only 3 of these animals had detectable serum viral RNA after challenge with wild-type dengue virus (DENV, suggesting protection of vaccinated animals to DENV infection. The vaccine induced statistically significant changes in 595 gene transcripts on days 1, 3, 5 and 7 as compared with baseline and placebo-treated animals. Genes involved in the type I interferon (IFN response, including IFI44, DDX58, MX1 and OASL, exhibited the highest fold-change in transcript abundance, and this response was strongest following double dose and subcutaneous (versus intradermal vaccine administration. In addition, modules of genes involved in antigen presentation, dendritic cell activation, and T cell activation and signaling were enriched following vaccination. Increased abundance of gene transcripts related to T cell activation on day 5, and the type I IFN response on day 7, were significantly correlated with the development of high neutralizing antibody titers on day 30.These results suggest that early transcriptional responses may be predictive of development of adaptive immunity to TDV

  16. Live attenuated African swine fever viruses as ideal tools to dissect the mechanisms involved in viral pathogenesis and immune protection.

    Science.gov (United States)

    Lacasta, Anna; Monteagudo, Paula L; Jiménez-Marín, Ángeles; Accensi, Francesc; Ballester, María; Argilaguet, Jordi; Galindo-Cardiel, Iván; Segalés, Joaquim; Salas, María L; Domínguez, Javier; Moreno, Ángela; Garrido, Juan J; Rodríguez, Fernando

    2015-11-20

    African swine fever virus (ASFV) is the causal agent of African swine fever, a hemorrhagic and often lethal porcine disease causing enormous economical losses in affected countries. Endemic for decades in most of the sub-Saharan countries and Sardinia, the risk of ASFV-endemicity in Europe has increased since its last introduction into Europe in 2007. Live attenuated viruses have been demonstrated to induce very efficient protective immune responses, albeit most of the time protection was circumscribed to homologous ASFV challenges. However, their use in the field is still far from a reality, mainly due to safety concerns. In this study we compared the course of the in vivo infection caused by two homologous ASFV strains: the virulent E75 and the cell cultured adapted strain E75CV1, obtained from adapting E75 to grow in the CV1 cell-line. Interestingly, the kinetics of both viruses not only differed on the clinical signs that they caused and in the virus loads found, but also in the immunological pathways activated throughout the infections. Furthermore, E75CV1 confirmed its protective potential against the homologous E75 virus challenge and allowed the demonstration of poor cross-protection against BA71, thus defining it as heterologous. The in vitro specificity of the CD8(+) T-cells present at the time of lethal challenge showed a clear activation against the homologous virus (E75) but not against BA71. These findings will be of utility for a better understanding of ASFV pathogenesis and for the rational designing of safe and efficient vaccines against this virus.

  17. Immunogenicity of live attenuated B. pertussis BPZE1 producing the universal influenza vaccine candidate M2e.

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    Hana Kammoun

    Full Text Available BACKGROUND: Intranasal delivery of vaccines directed against respiratory pathogens is an attractive alternative to parenteral administration. However, using this delivery route for inactivated vaccines usually requires the use of potent mucosal adjuvants, and no such adjuvant has yet been approved for human use. METHODOLOGY/PRINCIPAL FINDINGS: We have developed a live attenuated Bordetella pertussis vaccine, called BPZE1, and show here that it can be used to present the universal influenza virus epitope M2e to the mouse respiratory tract to prime for protective immunity against viral challenge. Three copies of M2e were genetically fused to the N-terminal domain of filamentous hemagglutinin (FHA and produced in recombinant BPZE1 derivatives in the presence or absence of endogenous full-length FHA. Only in the absence of FHA intranasal administration of the recombinant BPZE1 derivative induced antibody responses to M2e and effectively primed BALB/c mice for protection against influenza virus-induced mortality and reduced the viral load after challenge. Strong M2e-specific antibody responses and protection were observed after a single nasal administration with the recombinant BPZE1 derivative, followed by a single administration of M2e linked to a virus-like particle without adjuvant, whereas priming alone with the vaccine strain did not protect. CONCLUSIONS/SIGNIFICANCE: Using recombinant FHA-3M2e-producing BPZE1 derivatives for priming and the universal influenza M2e peptide linked to virus-like particles for boosting may constitute a promising approach for needle-free and adjuvant-free nasal vaccination against influenza.

  18. The live attenuated dengue vaccine TV003 elicits complete protection against dengue in a human challenge model.

    Science.gov (United States)

    Kirkpatrick, Beth D; Whitehead, Stephen S; Pierce, Kristen K; Tibery, Cecilia M; Grier, Palmtama L; Hynes, Noreen A; Larsson, Catherine J; Sabundayo, Beulah P; Talaat, Kawsar R; Janiak, Anna; Carmolli, Marya P; Luke, Catherine J; Diehl, Sean A; Durbin, Anna P

    2016-03-16

    A dengue human challenge model can be an important tool to identify candidate dengue vaccines that should be further evaluated in large efficacy trials in endemic areas. Dengue is responsible for about 390 million infections annually. Protective efficacy results for the most advanced dengue vaccine candidate (CYD) were disappointing despite its ability to induce neutralizing antibodies against all four dengue virus (DENV) serotypes. TV003 is a live attenuated tetravalent DENV vaccine currently in phase 2 evaluation. To better assess the protective efficacy of TV003, a randomized double-blind, placebo-controlled trial in which recipients of TV003 or placebo were challenged 6 months later with a DENV-2 strain, rDEN2Δ30, was conducted. The primary endpoint of the trial was protection against dengue infection, defined as rDEN2Δ30 viremia. Secondary endpoints were protection against rash and neutropenia. All 21 recipients of TV003 who were challenged with rDEN2Δ30 were protected from infection with rDEN2Δ30. None developed viremia, rash, or neutropenia after challenge. In contrast, 100% of the 20 placebo recipients who were challenged with rDEN2Δ30 developed viremia, 80% developed rash, and 20% developed neutropenia. TV003 induced complete protection against challenge with rDEN2Δ30 administered 6 months after vaccination. TV003 will be further evaluated in dengue-endemic areas. The controlled dengue human challenge model can accelerate vaccine development by evaluating the protection afforded by the vaccine, thereby eliminating poor candidates from further consideration before the initiation of large efficacy trials.

  19. Post-marketing safety surveillance for inactivated and live-attenuated Japanese encephalitis vaccines in China, 2008-2013.

    Science.gov (United States)

    Wu, Wendi; Liu, Dawei; Li, Keli; Nuorti, J Pekka; Nohynek, Hanna M; Xu, Disha; Ye, Jiakai; Zheng, Jingshan; Wang, Huaqing

    2017-06-22

    Two types of Japanese encephalitis (JE) vaccines, inactivated JE vaccine (JE-I) and live-attenuated JE vaccine (JE-L), are available and used in China. In particular, one JE-L, produced by a domestic manufacturer in China, was prequalified by WHO in 2013. We assessed the safety of JE vaccines in China during 2008-2013 using the Chinese National Adverse Events Following Immunization Information System (CNAEFIS) data. We retrieved AEFI reporting data about JE vaccines from CNAEFIS, 2008-2013, examined demographic characteristics of AEFI cases, and used administrative data on vaccine doses as denominator to calculate and compare crude reporting rates. We also used disproportionality reporting analysis between JE-I and JE-L to assess potential safety signals. A total of 34,879 AEFIs related with JE-I and JE-L were reported, with a ratio of male to female as 1.3:1; 361 (1.0%) cases were classified as serious. JE vaccines were administered concurrently with one or more other vaccines in 13,592 (39.0%) of cases. The overall AEFI reporting rates were 214.4 per million vaccination doses for JE-L and 176.9 for JE-I (rate ratio [RR]: 1.2, 95% confidence interval [CI]: 1.1-1.3) in 2010-2013. Febrile convulsions (FC) following JE-I was found as a signal of disproportionate reporting (SDR). However, there was no significant difference between the reporting rates of FC of JE-I and JE-L (0.3 per million vaccination doses for JE-L, 0.4 for JE-I, p=0.05). While our analysis did not find apparent safety concern of JE vaccines in China, further study should consider JE-I vaccines and febrile convulsion, and taking more sensitive methods to detect signals. Copyright © 2017. Published by Elsevier Ltd.

  20. Magnetic Resonance Imaging Findings of Mumps Meningoencephalitis with Bilateral Hippocampal Lesions without Preceding Acute Parotitis: A Case Report.

    Science.gov (United States)

    Woo, Ah Reum; Lee, Ha Young; Lim, Myung Kwan; Kang, Young Hye; Cho, Soon Gu; Choi, Seong Hye; Baek, Ji Hyeon

    2017-01-01

    Meningitis is a common central nervous system (CNS) complication of the mumps, a viral infection, but encephalitis and meningoencephalitis are less common in mumps. We describe magnetic resonance imaging findings of acute mumps meningoencephalitis in a 32-year-old male who showed bilateral hippocampal lesions without preceding parotitis. Although it is rare, hippocampal involvement should be considered a CNS complication of mumps infection.

  1. Magnetic resonance imaging findings of mumps meningoencephalitis with bilateral hippocampal lesions without preceding acute parotitis: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Woo, Ah Reum; Lee, Ha Young; Lim, Myung Kwan; Kang, Young Hye; Cho, Soon Gu; Choi, Seong Hye; Baek, Ji Hyeon [Inha University School of Medicine, Incheon (Korea, Republic of)

    2017-04-15

    Meningitis is a common central nervous system (CNS) complication of the mumps, a viral infection, but encephalitis and meningoencephalitis are less common in mumps. We describe magnetic resonance imaging findings of acute mumps meningoencephalitis in a 32-year-old male who showed bilateral hippocampal lesions without preceding parotitis. Although it is rare, hippocampal involvement should be considered a CNS complication of mumps infection.

  2. Generation and preclinical evaluation of a DENV-1/2 prM+E chimeric live attenuated vaccine candidate with enhanced prM cleavage.

    Science.gov (United States)

    Keelapang, Poonsook; Nitatpattana, Narong; Suphatrakul, Amporn; Punyahathaikul, Surat; Sriburi, Rungtawan; Pulmanausahakul, Rojjanaporn; Pichyangkul, Sathit; Malasit, Prida; Yoksan, Sutee; Sittisombut, Nopporn

    2013-10-17

    In the absence of a vaccine or sustainable vector control measures, illnesses caused by dengue virus infection remain an important public health problem in many tropical countries. During the export of dengue virus particles, furin-mediated cleavage of the prM envelope protein is usually incomplete, thus generating a mixture of immature, partially mature and mature extracellular particles. Variations in the arrangement and conformation of the envelope proteins among these particles may be associated with their different roles in shaping the antibody response. In an attempt to improve upon live, attenuated dengue vaccine approaches, a mutant chimeric virus, with enhanced prM cleavage, was generated by introducing a cleavage-enhancing substitution into a chimeric DENV-1/2 virus genome, encoding the prM+E sequence of a recent DENV-1 isolate under an attenuated DENV-2 genetic background. A modest increase in virus specific infectivity observed in the mutant chimeric virus affected neither the attenuation phenotype, when assessed in the suckling mouse neurovirulence model, nor multiplication in mosquitoes. The two chimeric viruses induced similar levels of anti-DENV-1 neutralizing antibody response in mice and rhesus macaques, but more efficient control of viremia during viral challenge was observed in macaques immunized with the mutant chimeric virus. These results indicate that the DENV-1/2 chimeric virus, with enhanced prM cleavage, could be useful as an alternative live, attenuated vaccine candidate for further tests in humans.

  3. Next-Generation Bacillus anthracis Live Attenuated Spore Vaccine Based on the htrA(-) (High Temperature Requirement A) Sterne Strain.

    Science.gov (United States)

    Chitlaru, Theodor; Israeli, Ma'ayan; Bar-Haim, Erez; Elia, Uri; Rotem, Shahar; Ehrlich, Sharon; Cohen, Ofer; Shafferman, Avigdor

    2016-01-06

    Anthrax is a lethal disease caused by the gram-positive spore-producing bacterium Bacillus anthracis. Live attenuated vaccines, such as the nonencapsulated Sterne strain, do not meet the safety standards mandated for human use in the Western world and are approved for veterinary purposes only. Here we demonstrate that disrupting the htrA gene, encoding the chaperone/protease HtrA (High Temperature Requirement A), in the virulent Bacillus anthracis Vollum strain results in significant virulence attenuation in guinea pigs, rabbits and mice, underlying the universality of the attenuated phenotype associated with htrA knockout. Accordingly, htrA disruption was implemented for the development of a Sterne-derived safe live vaccine compatible with human use. The novel B. anthracis SterneΔhtrA strain secretes functional anthrax toxins but is 10-10(4)-fold less virulent than the Sterne vaccine strain depending on animal model (mice, guinea pigs, or rabbits). In spite of this attenuation, double or even single immunization with SterneΔhtrA spores elicits immune responses which target toxaemia and bacteremia resulting in protection from subcutaneous or respiratory lethal challenge with a virulent strain in guinea pigs and rabbits. The efficacy of the immune-protective response in guinea pigs was maintained for at least 50 weeks after a single immunization.

  4. A live attenuated H7N7 candidate vaccine virus induces neutralizing antibody that confers protection from challenge in mice, ferrets and monkeys

    Science.gov (United States)

    A live attenuated H7N7 candidate vaccine virus was generated by reverse genetics using the modified hemagglutinin (HA) and neuraminidase (NA) genes of HP A/Netherlands/219/03 (NL/03) (H7N7) wild-type (wt) virus and the six internal protein genes of the cold-adapted (ca) A/Ann Arbor/6/60 ca (AA ca) (...

  5. The new temperature-sensitive mutation PA-F35S for developing recombinant avian live attenuated H5N1 influenza vaccine

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    Zhang Wenting

    2012-05-01

    Full Text Available Abstract Background H5N1 highly pathogenic avian influenza virus (HPAIV is continuously circulating in many Asian countries and threatening poultry industry and human population. Vaccination is the best strategy to control H5N1 HPAIV infection in poultry and transmission to human population. The aim of this study is to identify new temperature-sensitive (ts mutations for developing recombinant avian live attenuated H5N1 influenza vaccine. Findings A “6 + 2” recombinant virus C4/W1 that contained NA gene and modified HA gene from virus A/chicken/Hubei/327/2004 (H5N1 (C4, and six internal genes from virus A/duck/Hubei/W1/2004 (H9N2 (W1 was generated using reverse genetics and subsequently passaged in chicken eggs at progressively lower temperatures (32°C, 28°C and 25°C. The resulting virus acquired ts phenotype and one of its amino acid mutations, PA (F35S, was identified as ts mutation. Furthermore, when used as live attenuated vaccine, the recombinant virus with this ts mutation PA (F35S provided efficient protection for chickens against H5N1 HPAIV infection. Conclusions These findings highlight the potential of the new ts mutation PA (F35S in developing recombinant avian live attenuated H5N1 influenza vaccine.

  6. Is it Right Time to Introduce Mumps Vaccine in Indias Universal Immunization Program?

    Science.gov (United States)

    Vaidya, S R; Hamde, V S

    2016-06-08

    Measles, mumps and rubella are vaccine preventable diseases. However, morbidity and mortality due to these diseases remain largely unnoticed in India. Measles has received much attention; mumps and rubella still need to garner attention. According to the World Health Organization, near-elimination of mumps could be achieved by maintaining high vaccine coverage using a two-dose strategy. However, Government of India has not yet decided on mumps vaccine. In this review, we have reviewed sero-prevalence studies, vaccine studies, outbreak investigations, virus isolation and virus genotyping studies on mumps. Overall, mumps seems to be a significant public health problem in India, but does not garner attention due to the absence of a surveillance and documentation system. Thus, inclusion of mumps antigen in the Universal immunization program would have added advantages, the economic burden imposed by the cost of the vaccine offset by a reduction in disease burden.

  7. Dietary live yeast and mannan-oligosaccharide supplementation attenuate intestinal inflammation and barrier dysfunction induced by Escherichia coli in broilers.

    Science.gov (United States)

    Wang, Weiwei; Li, Zhui; Han, Qiqi; Guo, Yuming; Zhang, Bo; D'inca, Romain

    2016-12-01

    The effects of live yeast (LY) and mannan-oligosaccharide (MOS) supplementation on intestinal disruption induced by Escherichia coli in broilers were investigated. The experimental design was a 3×2 factorial arrangement with three dietary treatments (control, 0·5 g/kg LY (Saccharomyces cerevisiae, 1·0×1010 colony-forming units/g), 0·5 g/kg MOS) and two immune treatments (with or without E. coli challenge from 7 to 11 d of age). Samples were collected at 14 d of age. The results showed that E. coli challenge impaired (P<0·05) growth performance during the grower period (1-21 d) and the overall period (1-35 d) of broilers, increased (P<0·05) serum endotoxin and diamine oxidase levels coupled with ileal myeloperoxidase and lysozyme activities, whereas reduced (P<0·05) maltase activity, and compromised the morphological structure of the ileum. Besides, it increased (P<0·05) the mRNA expressions of several inflammatory genes and reduced occludin expression in the ileum. Dietary treatment with both LY and MOS reduced (P<0·05) serum diamine oxidase and ileal myeloperoxidase levels, but elevated villus height (P<0·10) and the ratio of villus height:crypt depth (P<0·05) of the ileum. It also alleviated (P<0·05) E. coli-induced increases (P<0·05) in ileal Toll-like receptor 4, NF-κ B and IL-1 β expressions. Moreover, LY supplementation reduced (P<0·05) feed conversion ratio of birds during the grower period and enhanced (P<0·05) the community diversity (Shannon and Simpson indices) of ileal microbiota, whereas MOS addition counteracted (P<0·05) the decreased ileal IL-10 and occludin expressions in challenged birds. In conclusion, both LY and MOS supplementation could attenuate E. coli-induced intestinal disruption by alleviating intestinal inflammation and barrier dysfunction in broilers. Moreover, LY addition could improve intestinal microbial community structure and feed efficiency of broilers.

  8. Safety Overview of a Recombinant Live-Attenuated Tetravalent Dengue Vaccine: Pooled Analysis of Data from 18 Clinical Trials.

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    Sophia Gailhardou

    2016-07-01

    Full Text Available A recombinant live attenuated tetravalent dengue vaccine (CYD-TDV has been shown to be efficacious in preventing virologically-confirmed dengue disease, severe dengue disease and dengue hospitalization in children aged 2-16 years in Asia and Latin America. We analyzed pooled safety data from 18 phase I, II and III clinical trials in which the dengue vaccine was administered to participants aged 2-60 years, including long-term safety follow-up in three efficacy trials. The participants were analyzed according to their age at enrollment. The percentage of participants aged 2-60 years reporting ≥1 solicited injection-site or systemic reactions was slightly higher in the CYD-TDV group than in the placebo group. The most common solicited injection-site reactions were pain. Headache and malaise were the most common solicited systemic reactions. In both groups 0.3% of participants discontinued for safety reasons. The most common unsolicited adverse events were injection-site reactions, gastrointestinal disorders, and infections. Reactogenicity did not increase with successive doses of CYD-TDV. The frequency and nature of SAEs occurring within 28 days of any dose were similar in the CYD-TDV and placebo groups and were common medical conditions that could be expected as a function of age. Baseline dengue virus serostatus did not appear to influence the safety profile. No vaccine-related anaphylactic reactions, neurotropic events or viscerotropic events were reported. In year 3 after dose 1, an imbalance for dengue hospitalization, including for severe dengue, observed in participants aged <9 years in the CYD-TDV group compared with the placebo group was not observed for participants aged ≥9 years. In Year 4, this imbalance in participants aged <9 years was less marked, giving an overall lower risk of dengue hospitalization or severe dengue from dose 1 to Year 4 in the CYD-TDV group. These results have contributed to the definition of the target

  9. Mumps, measles and rubella vaccination in children with PFAPA syndrome.

    Science.gov (United States)

    Kraszewska-G Omba, Barbara; Matkowska-Kocjan, Agnieszka; Mi Kiewicz, Katarzyna; Szyma Ska-Toczek, Zofia; Wójcik, Marta; Bany, Dorota; Szenborn, Leszek

    2016-11-21

    There is no published data regarding immunologic response to vaccinations in children with PFAPA syndrome (periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis). The aim of this study was to evaluate mumps, measles and rubella immunity in children with PFAPA. 31 children with PFAPA syndrome and 22 healthy children (control group - CG) were recruited to the study. All children were previously vaccinated with one dose of MMR vaccine according to the Polish obligatory vaccination schedule. The patients from both groups were evaluated for anti-measles, anti-mumps and anti-rubella IgG antibodies concentrations (ELISA tests; the reference values for protective antibody levels were 150IU/L, 16RU/L and 11IU/ml respectively). The percentage of patients with protective antibodies levels was as follows: measles - 93.55% of PFAPA and 95.45% of CG patients (p=0.77); mumps - 74.19% of PFAPA and 95.45% of CG patients (p=0.02); rubella - 80.65% of PFAPA and 90.9% of CG patients (p=0.30). Children with PFAPA syndrome present a good response to the measles and rubella component of the MMR vaccine, however immunity against mumps after one dose of MMR may not be sufficient. Further investigation concerning immunity against vaccine-preventable diseases and the safety of vaccinations in children with periodic fever syndromes is required. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Ultrasonographic Findings of Mumps Orchitis and Epididymo-Orchitis

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    Ihn, Yeon Kwon; Chung, Jae Joon; Kim, Myeong Jin; Yoo, Hyung Sik; Lee, Jong Tae [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    1996-06-15

    To determine ultrasonographic findings of mumps epididymo-orchitis to differentiate from other causes of epididymo-orchitis. We retrospectively analyzed the sonographic findings of 11 cases of mumps epididymo-orchitis in 10 patients. US findings were analyzed in terms of echogenicity, size, hydrocele, and calcification. The age of patients ranged from 12 to 27 years (average 16.6 years). A total of 11 lesions were involved testis : 2 lesions were located in left, 7 lesions in right, and bilaterally inone patient. Sonographic findings consisted of diffusely enlarged homogenous hypoechoic in 6 cases, diffusely enlarged in homogenous hypoechoic in 3 cases, and diffusely enlarged isoechoic testis in 2 cases. A total of 7 cases were involved epididymis : 5 cases were located in the head, and 2 in the tail. The sonographic finding of epididymitis was enlarged epididymis with heterogeneous hypoechoic pattern. The hydroceles were also seen in 5 cases. It is difficult to differentiate mumps epidydimo-orchitis from other infectiou sepididymo-orchitis only on the basis of ultrasonographic findings, but the clinical history of mumps can be helpful in diagnosis of this disease

  11. Rescue of mumps virus from cDNA.

    Science.gov (United States)

    Clarke, D K; Sidhu, M S; Johnson, J E; Udem, S A

    2000-05-01

    A complete DNA copy of the genome of a Jeryl Lynn strain of mumps virus (15,384 nucleotides) was assembled from cDNA fragments such that an exact antigenome RNA could be generated following transcription by T7 RNA polymerase and cleavage by hepatitis delta virus ribozyme. The plasmid containing the genome sequence, together with support plasmids which express mumps virus NP, P, and L proteins under control of the T7 RNA polymerase promoter, were transfected into A549 cells previously infected with recombinant vaccinia virus (MVA-T7) that expressed T7 RNA polymerase. Rescue of infectious virus from the genome cDNA was demonstrated by amplification of mumps virus from transfected-cell cultures and by subsequent consensus sequencing of reverse transcription-PCR products generated from infected-cell RNA to verify the presence of specific nucleotide tags introduced into the genome cDNA clone. The only coding change (position 8502, A to G) in the cDNA clone relative to the consensus sequence of the Jeryl Lynn plaque isolate from which it was derived, resulting in a lysine-to-arginine substitution at amino acid 22 of the L protein, did not prevent rescue of mumps virus, even though an amino acid alignment for the L proteins of paramyxoviruses indicates that lysine is highly conserved at that position. This system may provide the basis of a safe and effective virus vector for the in vivo expression of immunologically and biologically active proteins, peptides, and RNAs.

  12. Low vaccine efficacy of mumps component among MMR vaccine recipients in Chennai, India

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    Jeevan Malaiyan

    2014-01-01

    Full Text Available Introduction of MMR vaccine was believed to have resulted in a decline in the incidence of measles, mumps and rubella infections. However, recent reports suggest the re-emergence of mumps infection worldwide in the vaccinated populations. It was proposed that the reason for this re-emergence was poor efficacy of MMR vaccine. The present study was aimed to investigate mumps infection in MMR vaccinated and non-vaccinated populations in Chennai, India. Blood samples were collected from acute mumps cases (n=74, 42<12 yr age, 54% males and investigated for IgM antibody against mumps, IgG antibody against measles, mumps and rubella viruses by ELISA. Sixty seven (91% patients had received MMR vaccine. All the 67 vaccinated cases were positive for parotitis, and mumps IgM. However, only 10 (15% were positive for IgG. All samples (100% were positive for rubella and measles IgG. These findings showed the occurrence of mumps infection among MMR vaccinated individuals in Chennai, India. The MMR vaccine failed to generate anti-mumps IgG. The reason may be low vaccine efficacy of the mumps component of the MMR vaccine used.

  13. Risks associated with the use of live-attenuated vaccine poliovirus strains and the strategies for control and eradication of paralytic poliomyelitis.

    Science.gov (United States)

    Pliaka, Vaia; Kyriakopoulou, Zaharoula; Markoulatos, Panayotis

    2012-05-01

    The Global Polio Eradication Initiative was launched in 1988 with the aim to eliminate paralytic poliomyelitis. Two effective vaccines are available: inactivated polio vaccine (IPV) and oral polio vaccine (OPV). Since 1964, OPV has been used instead of IPV in most countries due to several economic and biological advantages. However, in rare cases, the live-attenuated Sabin strains of OPV revert to neurovirulence and cause vaccine-associated paralytic poliomyelitis in vaccinees or lead to emergence of vaccine-derived poliovirus strains. Attenuating mutations and recombination events have been associated with the reversion of vaccine strains to neurovirulence. The substitution of OPV with an improved new-generation IPV and the availability of new specific drugs against polioviruses are considered as future strategies for outbreak control and the eradication of paralytic poliomyelitis worldwide.

  14. Construction, characterization and preclinical evaluation of MTBVAC, the first live-attenuated M. tuberculosis-based vaccine to enter clinical trials.

    Science.gov (United States)

    Arbues, Ainhoa; Aguilo, Juan I; Gonzalo-Asensio, Jesus; Marinova, Dessislava; Uranga, Santiago; Puentes, Eugenia; Fernandez, Conchita; Parra, Alberto; Cardona, Pere Joan; Vilaplana, Cristina; Ausina, Vicente; Williams, Ann; Clark, Simon; Malaga, Wladimir; Guilhot, Christophe; Gicquel, Brigitte; Martin, Carlos

    2013-10-01

    The development of a new tuberculosis vaccine is an urgent need due to the failure of the current vaccine, BCG, to protect against the respiratory form of the disease. MTBVAC is an attenuated Mycobacterium tuberculosis vaccine candidate genetically engineered to fulfil the Geneva consensus requirements to enter human clinical trials. We selected a M. tuberculosis clinical isolate to generate two independent deletions without antibiotic-resistance markers in the genes phoP, coding for a transcription factor key for the regulation of M. tuberculosis virulence, and fadD26, essential for the synthesis of the complex lipids phthiocerol dimycocerosates (DIM), one of the major mycobacterial virulence factors. The resultant strain MTBVAC exhibits safety and biodistribution profiles similar to BCG and confers superior protection in preclinical studies. These features have enabled MTBVAC to be the first live attenuated M. tuberculosis vaccine to enter clinical evaluation.

  15. Rational design of a live attenuated dengue vaccine: 2'-o-methyltransferase mutants are highly attenuated and immunogenic in mice and macaques.

    Directory of Open Access Journals (Sweden)

    Roland Züst

    Full Text Available Dengue virus is transmitted by Aedes mosquitoes and infects at least 100 million people every year. Progressive urbanization in Asia and South-Central America and the geographic expansion of Aedes mosquito habitats have accelerated the global spread of dengue, resulting in a continuously increasing number of cases. A cost-effective, safe vaccine conferring protection with ideally a single injection could stop dengue transmission. Current vaccine candidates require several booster injections or do not provide protection against all four serotypes. Here we demonstrate that dengue virus mutants lacking 2'-O-methyltransferase activity are highly sensitive to type I IFN inhibition. The mutant viruses are attenuated in mice and rhesus monkeys and elicit a strong adaptive immune response. Monkeys immunized with a single dose of 2'-O-methyltransferase mutant virus showed 100% sero-conversion even when a dose as low as 1,000 plaque forming units was administrated. Animals were fully protected against a homologous challenge. Furthermore, mosquitoes feeding on blood containing the mutant virus were not infected, whereas those feeding on blood containing wild-type virus were infected and thus able to transmit it. These results show the potential of 2'-O-methyltransferase mutant virus as a safe, rationally designed dengue vaccine that restrains itself due to the increased susceptibility to the host's innate immune response.

  16. A novel, live-attenuated vesicular stomatitis virus vector displaying conformationally intact, functional HIV-1 envelope trimers that elicits potent cellular and humoral responses in mice.

    Directory of Open Access Journals (Sweden)

    Svetlana Rabinovich

    Full Text Available Though vaccination with live-attenuated SIV provides the greatest protection from progressive disease caused by SIV challenge in rhesus macaques, attenuated HIV presents safety concerns as a vaccine; therefore, live viral vectors carrying HIV immunogens must be considered. We have designed a replication-competent vesicular stomatitis virus (VSV displaying immunogenic HIV-1 Env trimers and attenuating quantities of the native surface glycoprotein (G. The clade B Env immunogen is an Env-VSV G hybrid (EnvG in which the transmembrane and cytoplasmic tail regions are derived from G. Relocation of the G gene to the 5'terminus of the genome and insertion of EnvG into the natural G position induced a ∼1 log reduction in surface G, significant growth attenuation compared to wild-type, and incorporation of abundant EnvG. Western blot analysis indicated that ∼75% of incorporated EnvG was a mature proteolytically processed form. Flow cytometry showed that surface EnvG bound various conformationally- and trimer-specific antibodies (Abs, and in-vitro growth assays on CD4+CCR5+ cells demonstrated EnvG functionality. Neither intranasal (IN or intramuscular (IM administration in mice induced any observable pathology and all regimens tested generated potent Env-specific ELISA titers of 10(4-10(5, with an IM VSV prime/IN VSV boost regimen eliciting the highest binding and neutralizing Ab titers. Significant quantities of Env-specific CD4+ T cells were also detected, which were augmented as much as 70-fold by priming with IM electroporated plasmids encoding EnvG and IL-12. These data suggest that our novel vector can achieve balanced safety and immunogenicity and should be considered as an HIV vaccine platform.

  17. Development of prophylactic recombinant HPV58-attenuated Shigeila live vector vaccine and evaluation of its protective efficacy and immunogenicity in the guinea pig keratoconjunctivitis model

    Institute of Scientific and Technical Information of China (English)

    Wensheng Li; Hongli Liu; Xiaofeng Yang; Jin Zheng; Yili Wang; Lusheng Si

    2009-01-01

    To develop a prophylactic recombinant HPV58L1-attenuated Shigella live vector vaccine and evaluate its protective efficacy and immunogenicity in the guinea pig keratoconjunctivitis model, the HPV58L1 gene was cloned into vector pUCmt, and then subcloned into the suicide vector pCVD442. The recombinant plasmid pCVD442-HPV58L1 was introduced into attenuated Shigella (sf301:△virG) with the helper plasmid PRK2013 by filter mating. The positive colonies were harvested and confirmed by polymerase chain reaction. The expression of the HPV58L1 protein with a molecu-lar weight of 60 kDa was confirmed by western blot. The ability of the interested protein to self-assemble into virus-like particles was identified by transmission electron microscope, and murine erythrocyte hemagglu-tination assay. The guinea pig keratoconjunctivitis model was used to evaluate the protective efficacy and immunogenicity of the vaccine. Animal experiments showed that there was no keratoconjunctivitis occurred in the immunized group (HPV58-attenuated Shigella), and the serum levels of anti-HPV58L1-IgG and -IgA were obviously increased (P0.05). Enzyme-linked immunosorbent spot assay showed that HPV58L1-specific IgA-antibody-secreting cells (ASC) and IgG-ASC of spleen and lymph nodes were also obviously increased (P<0.01). In this study, a recombi-nant HPV58L1-attenuated Shigella live vector vaccine was successfully constructed, and it could induce strong humoral immune responses in the immunized animals, and induce protective antibody production.

  18. 国产水痘减毒活疫苗的稳定性观察%Stability of domestic live attenuated varicella vaccine

    Institute of Scientific and Technical Information of China (English)

    马相虎; 沈坚; 陈哲文; 王亮; 沈谊清; 晏子厚

    2014-01-01

    目的 观察国产水痘减毒活疫苗的稳定性.方法 取40批上海生物制品研究所有限责任公司(以下简称上海公司)2007~2013年生产的水痘减毒活疫苗,按照国家食品药品监督管理局批准的水痘减毒活疫苗注册标准和《中国药典》的要求进行各项检定:在0月进行热稳定性试验;在0和18月进行鉴别试验、物理检查、水分检测、无菌检查、异常毒性检查、牛血清白蛋白残留量检测、抗生素残留量检测(2010年10月以后生产的疫苗);在0、6、12、18月进行病毒滴定.结果 上海公司2007~2013年生产的水痘减毒活疫苗在有效期内各项指标检定结果均符合水痘减毒活疫苗注册标准和《中国药典》的相关要求.结论 上海公司生产的水痘减毒活疫苗质量稳定,安全有效.%Objective To evaluate the stability of domestic live attenuated varicella vaccine.Methods Forty batches of live attenuated varicella vaccine manufactured by Shanghai Institute of Biological Products Co.,Ltd.(SIBP) in 2007 ~ 2013 were subjected to overall control tests according to the standard for license of live attenuated varicella vaccine approved by the SFDA and the requirements in Chinese Pharmacopoeia (Volume Ⅲ,2010 edition).Heat stability test was performed at month 0,while identity test,physical examination,as well as tests for moisture,sterility,abnormal toxicity,residual bovine serum albumin and residual antibiotic (manufactured after October 2010) at months 0 and 18,and virus titration at months 0,6,12 and 18.Results All the quality indexes of live attenuated varicella vaccine manufactured by SIBP met the standard for license of live attenuated varicella vaccine and the requirements in Chinese Pharmacopoeia (Volume Ⅲ,2010 edition).Conclusion The live attenuated varicella vaccine manufactured by SIBP was stable,safe and effective.

  19. Determinants of students' willingness to accept a measles-mumps-rubella booster vaccination during a mumps outbreak: a cross-sectional study

    NARCIS (Netherlands)

    Donkers, H.W.; Hautvast, J.L.A.; Akkermans, R.P.; Swaan, C.M.; Ruijs, W.L.M.; Hulscher, M.E.J.L.

    2015-01-01

    BACKGROUND: Despite high vaccination coverage, a mumps outbreak that affected mainly vaccinated university students and their contacts took place in the Netherlands in the period 2009-2012. We presented university students with a hypothetical case in which we offered them a measles, mumps, and rubel

  20. Determinants of students' willingness to accept a measles-mumps-rubella booster vaccination during a mumps outbreak: a cross-sectional study

    NARCIS (Netherlands)

    Donkers, H.W.; Hautvast, J.L.A.; Akkermans, R.P.; Swaan, C.M.; Ruijs, W.L.M.; Hulscher, M.E.J.L.

    2015-01-01

    BACKGROUND: Despite high vaccination coverage, a mumps outbreak that affected mainly vaccinated university students and their contacts took place in the Netherlands in the period 2009-2012. We presented university students with a hypothetical case in which we offered them a measles, mumps, and rubel

  1. ADCC develops over time during persistent infection with live-attenuated SIV and is associated with complete protection against SIV(mac251 challenge.

    Directory of Open Access Journals (Sweden)

    Michael D Alpert

    Full Text Available Live-attenuated strains of simian immunodeficiency virus (SIV routinely confer apparent sterilizing immunity against pathogenic SIV challenge in rhesus macaques. Understanding the mechanisms of protection by live-attenuated SIV may provide important insights into the immune responses needed for protection against HIV-1. Here we investigated the development of antibodies that are functional against neutralization-resistant SIV challenge strains, and tested the hypothesis that these antibodies are associated with protection. In the absence of detectable neutralizing antibodies, Env-specific antibody-dependent cell-mediated cytotoxicity (ADCC emerged by three weeks after inoculation with SIVΔnef, increased progressively over time, and was proportional to SIVΔnef replication. Persistent infection with SIVΔnef elicited significantly higher ADCC titers than immunization with a non-persistent SIV strain that is limited to a single cycle of infection. ADCC titers were higher against viruses matched to the vaccine strain in Env, but were measurable against viruses expressing heterologous Env proteins. In two separate experiments, which took advantage of either the strain-specificity or the time-dependent maturation of immunity to overcome complete protection against SIV(mac251 challenge, measures of ADCC activity were higher among the SIVΔnef-inoculated macaques that remained uninfected than among those that became infected. These observations show that features of the antibody response elicited by SIVΔnef are consistent with hallmarks of protection by live-attenuated SIV, and reveal an association between Env-specific antibodies that direct ADCC and apparent sterilizing protection by SIVΔnef.

  2. Nested PCR for rapid detection of mumps virus in cerebrospinal fluid from patients with neurological diseases.

    Science.gov (United States)

    Poggio, G P; Rodriguez, C; Cisterna, D; Freire, M C; Cello, J

    2000-01-01

    In this study, we have developed a reverse transcription (RT)-nested polymerase chain reaction (n-PCR) for the detection of mumps virus RNA in cerebrospinal fluid (CSF) from patients with neurological infections. A specific 112-bp fragment was amplified by this method with primers from the nucleoprotein of the mumps virus genome. The mumps virus RT-n-PCR was capable of detecting 0.001 PFU/ml and 0.005 50% tissue culture infective dose/ml. This method was found to be specific, since no PCR product was detected in each of the CSF samples from patients with proven non-mumps virus-related meningitis or encephalitis. Mumps virus RNA was detected in all 18 CSF samples confirmed by culture to be infected with mumps virus. Positive PCR results were obtained for the CSF of 26 of 28 patients that were positive for signs of mumps virus infection (i.e., cultivable virus from urine or oropharyngeal samples or positivity for anti-mumps virus immunoglobulin M) but without cultivable virus in their CSF. Overall, mumps virus RNA was detected in CSF of 96% of the patients with a clinical diagnosis of viral central nervous system (CNS) disease and confirmed mumps virus infection, while mumps virus was isolated in CSF of only 39% of the patients. Furthermore, in a retrospective study, we were able to detect mumps virus RNA in 25 of 55 (46%) CSF samples from patients with a clinical diagnosis of viral CNS disease and negative laboratory evidence of viral infection including mumps virus infection. The 25 patients represent 12% of the 236 patients who had a clinical diagnosis of viral CNS infections and whose CSF was examined at our laboratory for a 2-year period. The findings confirm the importance of mumps virus as a causative agent of CNS infections in countries with low vaccine coverage rates. In summary, our study demonstrates the usefulness of the mumps virus RT-n-PCR for the diagnosis of mumps virus CNS disease and suggests that this assay may soon become the "gold standard" test

  3. An integrated, multistudy analysis of the safety of Ann Arbor strain live attenuated influenza vaccine in children aged 2–17 years

    OpenAIRE

    Ambrose, Christopher S.; Yi, Tingting; Falloon, Judith

    2011-01-01

    Background Trivalent, Ann Arbor strain, live attenuated influenza vaccine (LAIV) is approved in several countries for use in eligible children aged ≥2 years. Objective To describe the safety of Ann Arbor strain LAIV in children aged 2–17 years. Methods An integrated analysis of randomized, controlled trials of LAIV. Results A total of 4245 and 10 693 children received ≥1 dose of LAIV in year 1 of 6 trivalent inactivated influenza vaccine (TIV)-controlled and 14 placebo-controlled studies, res...

  4. Field Trial of Attenuated Salmonella Typhi Live Oral Vaccine TY21A in Liquid and Enteric-Coated Formulations and Epidemiological Survey for Incidence of Diarrhea due to Shigella Species

    Science.gov (United States)

    1989-03-01

    AD-A248 309 till AD FIELD TRIAL OF ATTENUATED SALMONELLA TYPHI LIVE ORAL VACCINE TY21A IN LIQUID AND ENTERIC-COATED FORMULATIONS AND EPIDEMIOLOGICAL...024 11- TITLE WL-* .S-wrYCIAo40 (U) Field Trial of Attenuated Salmonella typhi Live Oral Vaccine Ty2la in Liquid and Enteric-Coated Formulations and...Clements ML, Lanata C, Rooney J, Germanier R, Chilean Typhoid Cormmittee. The efficacy of attenuated Salmonella typhi oral vaccine strain Ty2la evaluated in

  5. Guillain-Barré syndrome and ethylene diamine tetraacetic acid-dependent pseudothrombocytopenia associated with mumps.

    Science.gov (United States)

    Sawazaki, A; Nakamura, N; Jyokaji, H; Minami, S; Nakamura, S; Matsuda, T

    1996-12-01

    A 35-year-old man with Guillain-Barré syndrome and ethylene diamine tetraacetic acid (EDTA)-dependent pseudothrombocytopenia associated with serologically-confirmed mumps is presented. A polyneuropathy developed 18 days after the onset of mumps, that improved with plasmapheresis. A decreased platelet count was observed 25 days after the onset of mumps attributed to platelet agglutination in blood anticoagulated with EDTA, and the agglutination was prevented by other anticoagulants. Guillain-Barré syndrome associated with mumps is rare and EDTA-dependent pseudothrombocytopenia following mumps has never been documented. This represents the first report of Guillain-Barré syndrome and EDTA-dependent pseudothrombocytopenia following mumps. Furthermore, our findings suggest activation of the humoral immune response as a potential pathogenesis.

  6. Introducing combined measles, mumps and rubella vaccine in Chandigarh, India: issues and concerns.

    Science.gov (United States)

    Bhatnagar, Nidhi; Kaur, Ravneet; Gupta, Madhu; Sharma, Deepak

    2014-06-01

    Cyclical outbreaks of mumps have been noticed across Chandigarh city during winter months. Chandigarh does not provide measles, mumps and rubella (MMR) vaccination in the State immunization schedule. Epidemiological shift in age at diagnosis of mumps was noticed with higher incidence in older children and adults. Increased occurrence of complications can be predicted with this age shift. Silent burden of rubella with serious outcomes in newborns further strengthen the case for MMR vaccine inclusion in routine immunization program of Chandigarh.

  7. Mumps vaccine associated orchitis: Evidence supporting a potential immune-mediated mechanism.

    Science.gov (United States)

    Clifford, Vanessa; Wadsley, Jane; Jenner, Bernard; Buttery, Jim P

    2010-03-19

    We report 3 cases of orchitis following vaccination with mumps-measles-rubella (MMR) vaccine, two with an onset within 3 days following vaccination. Orchitis is a common complication of mumps infection, particularly in post-pubertal males, and is also recognized as a very rare complication of mumps vaccination. These cases, discussed together with a comprehensive review of the existing literature regarding post-vaccine orchitis, highlight uncertainty regarding the pathogenesis of post-vaccine orchitis.

  8. CD8+ T-cell Responses in Flavivirus-Naive Individuals Following Immunization with a Live-Attenuated Tetravalent Dengue Vaccine Candidate.

    Science.gov (United States)

    Chu, Haiyan; George, Sarah L; Stinchcomb, Dan T; Osorio, Jorge E; Partidos, Charalambos D

    2015-11-15

    We are developing a live-attenuated tetravalent dengue vaccine (TDV) candidate based on an attenuated dengue 2 virus (TDV-2) and 3 chimeric viruses containing the premembrane and envelope genes of dengue viruses (DENVs) -1, -3, and -4 expressed in the context of the attenuated TDV-2 genome (TDV-1, TDV-3, and TDV-4, respectively). In this study, we analyzed and characterized the CD8(+) T-cell response in flavivirus-naive human volunteers vaccinated with 2 doses of TDV 90 days apart via the subcutaneous or intradermal routes. Using peptide arrays and intracellular cytokine staining, we demonstrated that TDV elicits CD8(+) T cells targeting the nonstructural NS1, NS3, and NS5 proteins of TDV-2. The cells were characterized by the production of interferon-γ, tumor necrosis factor-α, and to a lesser extent interleukin-2. Responses were highest on day 90 after the first dose and were still detectable on 180 days after the second dose. In addition, CD8(+) T cells were multifunctional, producing ≥2 cytokines simultaneously, and cross-reactive to NS proteins of the other 3 DENV serotypes. Overall, these findings describe the capacity of our candidate dengue vaccine to elicit cellular immune responses and support the further evaluation of T-cell responses in samples from future TDV clinical trials.

  9. Development of a dual-protective live attenuated vaccine against H5N1 and H9N2 avian influenza viruses by modifying the NS1 gene.

    Science.gov (United States)

    Choi, Eun-hye; Song, Min-Suk; Park, Su-Jin; Pascua, Philippe Noriel Q; Baek, Yun Hee; Kwon, Hyeok-il; Kim, Eun-Ha; Kim, Semi; Jang, Hyung-Kwan; Poo, Haryoung; Kim, Chul-Joong; Choi, Young Ki

    2015-07-01

    An increasing number of outbreaks of avian influenza H5N1 and H9N2 viruses in poultry have caused serious economic losses and raised concerns for human health due to the risk of zoonotic transmission. However, licensed H5N1 and H9N2 vaccines for animals and humans have not been developed. Thus, to develop a dual H5N1 and H9N2 live-attenuated influenza vaccine (LAIV), the HA and NA genes from a virulent mouse-adapted avian H5N2 (A/WB/Korea/ma81/06) virus and a recently isolated chicken H9N2 (A/CK/Korea/116/06) virus, respectively, were introduced into the A/Puerto Rico/8/34 backbone expressing truncated NS1 proteins (NS1-73, NS1-86, NS1-101, NS1-122) but still possessing a full-length NS gene. Two H5N2/NS1-LAIV viruses (H5N2/NS1-86 and H5N2/NS1-101) were highly attenuated compared with the full-length and remaining H5N2/NS-LAIV viruses in a mouse model. Furthermore, viruses containing NS1 modifications were found to induce more IFN-β activation than viruses with full-length NS1 proteins and were correspondingly attenuated in mice. Intranasal vaccination with a single dose (10(4.0) PFU/ml) of these viruses completely protected mice from a lethal challenge with the homologous A/WB/Korea/ma81/06 (H5N2), heterologous highly pathogenic A/EM/Korea/W149/06 (H5N1), and heterosubtypic highly virulent mouse-adapted H9N2 viruses. This study clearly demonstrates that the modified H5N2/NS1-LAIV viruses attenuated through the introduction of mutations in the NS1 coding region display characteristics that are desirable for live attenuated vaccines and hold potential as vaccine candidates for mammalian hosts.

  10. Vaccination of children with a live-attenuated, intranasal influenza vaccine – analysis and evaluation through a Health Technology Assessment

    Directory of Open Access Journals (Sweden)

    Andersohn, Frank

    2014-10-01

    Full Text Available [english] Background: Influenza is a worldwide prevalent infectious disease of the respiratory tract annually causing high morbidity and mortality in Germany. Influenza is preventable by vaccination and this vaccination is so far recommended by the (STIKO as a standard vaccination for people from the age of 60 onwards. Up to date a parenterally administered trivalent inactivated vaccine (TIV has been in use almost exclusively. Since 2011 however a live-attenuated vaccine (LAIV has been approved additionally. Consecutively, since 2013 the STIKO recommends LAIV (besides TIV for children from 2 to 17 years of age, within the scope of vaccination by specified indications. LAIV should be preferred administered in children from 2 to 6 of age. The objective of this Health Technology Assessment (HTA is to address various research issues regarding the vaccination of children with LAIV. The analysis was performed from a medical, epidemiological and health economic perspective, as well as from an ethical, social and legal point of view.Method: An extensive systematic database research was performed to obtain relevant information. In addition a supplementary research by hand was done. Identified literature was screened in two passes by two independent reviewers using predefined inclusion and exclusion criteria. Included literature was evaluated in full-text using acknowledged standards. Studies were graded with the highest level of evidence (1++, if they met the criteria of Results: For the medical section, the age of the study participants ranges from 6 months to 17 years. Regarding study efficacy, in children aged 6 months to ≤7 years, LAIV is superior to placebo as well as to a vac-cination with TIV (Relative Risk Reduction – RRR – of laboratory confirmed influenza infection approx. 80% and 50%, respectively. In children aged >7 to 17 years (= 18th year of their lives, LAIV is superior to a vaccination with TIV (RRR 32%. For this age group, no

  11. Vaccination of children with a live-attenuated, intranasal influenza vaccine - analysis and evaluation through a Health Technology Assessment.

    Science.gov (United States)

    Andersohn, Frank; Bornemann, Reinhard; Damm, Oliver; Frank, Martin; Mittendorf, Thomas; Theidel, Ulrike

    2014-01-01

    Influenza is a worldwide prevalent infectious disease of the respiratory tract annually causing high morbidity and mortality in Germany. Influenza is preventable by vaccination and this vaccination is so far recommended by the The German Standing Committee on Vaccination (STIKO) as a standard vaccination for people from the age of 60 onwards. Up to date a parenterally administered trivalent inactivated vaccine (TIV) has been in use almost exclusively. Since 2011 however a live-attenuated vaccine (LAIV) has been approved additionally. Consecutively, since 2013 the STIKO recommends LAIV (besides TIV) for children from 2 to 17 years of age, within the scope of vaccination by specified indications. LAIV should be preferred administered in children from 2 to 6 of age. The objective of this Health Technology Assessment (HTA) is to address various research issues regarding the vaccination of children with LAIV. The analysis was performed from a medical, epidemiological and health economic perspective, as well as from an ethical, social and legal point of view. An extensive systematic database research was performed to obtain relevant information. In addition a supplementary research by hand was done. Identified literature was screened in two passes by two independent reviewers using predefined inclusion and exclusion criteria. Included literature was evaluated in full-text using acknowledged standards. Studies were graded with the highest level of evidence (1++), if they met the criteria of European Medicines Agency (EMA)-Guidance: Points to consider on applications with 1. meta-analyses; 2. one pivotal study. For the medical section, the age of the study participants ranges from 6 months to 17 years. Regarding study efficacy, in children aged 6 months to ≤7 years, LAIV is superior to placebo as well as to a vac-cination with TIV (Relative Risk Reduction - RRR - of laboratory confirmed influenza infection approx. 80% and 50%, respectively). In children aged >7 to 17

  12. Anti-mumps virus activity by extracts of Mimosa pudica, a unique Indian medicinal plant.

    Science.gov (United States)

    Malayan, Jeevan; Selvaraj, Balaji; Warrier, Aparna; Shanmugam, Sambantham; Mathayan, Manikannan; Menon, Thangam

    2013-09-01

    Mumps is an acute and self-limiting disease characterized by parotitis, however in some cases it leads to aseptic meningitis, deafness, encephalitis and orchitis, which is a serious health concern. MMR vaccination was successful in eradicating the disease however, recent reports question the efficacy of MMR vaccine and countless outbreaks are observed in vaccinated populations throughout the world. Lack of specific treatment methods for mumps infection and inefficiency of MMR vaccine in vaccinated populations accentuates the need for the development of novel drugs to control mumps virus mediated serious infections. It was with this backdrop of information that the anti-mumps virus activity of Mimosa pudica was evaluated. Suspected mumps cases were collected to isolate a standard mumps virus by systematic laboratory testing which included IgM antibody assays, virus isolation, RT-PCR and phylogenetic analysis. The virus was quantified by TCID50 assay and anti-mumps virus property was evaluated by CPE reduction assay and cytotoxicity of the extract was measured by MTT assay and phytochemical analysis was done by gas chromatography-mass spectroscopy. The RT-PCR and phylogenetic tree analysis of the SH gene sequence of the clinical isolate showed it to be mumps virus genotype C. 150 μg/ml concentration of M. pudica completely inhibited mumps virus and the drug was found to be non-toxic up to 2 mg/ml. M. pudica was thus found to be a potent inhibitor of MuV.

  13. Long term follow-up study to evaluate immunogenicity and safety of a single dose of live attenuated hepatitis a vaccine in children.

    Science.gov (United States)

    Mitra, Monjori; Shah, Nitin; Faridi, Mma; Ghosh, Apurba; Sankaranarayanan, V S; Aggarwal, Anju; Chatterjee, Suparna; Bhattacharyya, Nisha; Kadhe, Ganesh; Vishnoi, Gaurav; Mane, Amey

    2015-01-01

    Worldwide, viral hepatitis continues to be a cause of considerable morbidity and mortality. Mass immunization with a single dose of live attenuated HAV has been shown to significantly reduce disease burden in the community. This was a phase IV, 5-year follow up study carried out at 4 centers (Kolkata, Delhi, Mumbai and Chennai) across India. The subjects with antibody titer 20 mIU/mL). The seroconversion rates considering seroprotection levels of anti-HAV antibody titer >20 mIU/mL, following vaccination starting from 6 weeks, 6 months, 12 months, 24 months, 36 months, 48 months and 60 months were 95.1%, 97.9%, 98.3%, 96.2%, 97.8%, 92.6% and 97.3%, respectively. The geometric mean concentration (GMC) over the years increased from 64.9 mIU/mL at 6 weeks to 38.1 mIU/mL and 135.2 mIU/mL at 6 months and 12 months, respectively and was maintained at 127.1 mIU/mL at 60 months. In conclusion, the result of this 5-year follow up study showed that the single dose of live attenuated vaccine is well tolerated and provides long-term immunogenicity in healthy Indian children.

  14. Improved hatchability and efficient protection after in ovo vaccination with live-attenuated H7N2 and H9N2 avian influenza viruses

    Directory of Open Access Journals (Sweden)

    Shao Hongxia

    2011-01-01

    Full Text Available Abstract Mass in ovo vaccination with live attenuated viruses is widely used in the poultry industry to protect against various infectious diseases. The worldwide outbreaks of low pathogenic and highly pathogenic avian influenza highlight the pressing need for the development of similar mass vaccination strategies against avian influenza viruses. We have previously shown that a genetically modified live attenuated avian influenza virus (LAIV was amenable for in ovo vaccination and provided optimal protection against H5 HPAI viruses. However, in ovo vaccination against other subtypes resulted in poor hatchability and, therefore, seemed impractical. In this study, we modified the H7 and H9 hemagglutinin (HA proteins by substituting the amino acids at the cleavage site for those found in the H6 HA subtype. We found that with this modification, a single dose in ovo vaccination of 18-day old eggs provided complete protection against homologous challenge with low pathogenic virus in ≥70% of chickens at 2 or 6 weeks post-hatching. Further, inoculation of 19-day old egg embryos with 106 EID50 of LAIVs improved hatchability to ≥90% (equivalent to unvaccinated controls with similar levels of protection. Our findings indicate that the strategy of modifying the HA cleavage site combined with the LAIV backbone could be used for in ovo vaccination against avian influenza. Importantly, with protection conferred as early as 2 weeks post-hatching, with this strategy birds would be protected prior to or at the time of delivery to a farm or commercial operation.

  15. Construction of Prophylactic Human Papillomavirus Type 16 L1 Capsid Protein Vaccine Delivered by Live Attenuated Shigella flexneri Strain sh42

    Institute of Scientific and Technical Information of China (English)

    Xiao-Feng YANG; Xin-Zhong QU; Kai WANG; Jin ZHENG; Lü-Sheng SI; Xiao-Ping DONG; Yi-Li WANG

    2005-01-01

    To express human papillomavirus (HPV) L1 capsid protein in the recombinant strain of Shigella and study the potential of a live attenuated Shigella-based HPV prophylactic vaccine in preventing HPV infection, the icsA/virG fragment of Shigella-based prokaryotic expression plasmid pHS3199 was constructed.HPV type 16 L 1 (HPV 16L 1) gene was inserted into plasmid pHS 3199 to form the pHS3199-HPV 16L1construct, and pHS3199-HPV16L1 was electroporated into a live attenuated Shigella strain sh42. Western blotting analysis showed that HPV 16L1 could be expressed stably in the recombinant strain sh42-HPV 16L1.Sereny test results were negative, which showed that the sh42-HPV16L1 lost virulence. However, the attenuated recombinant strain partially maintained the invasive property as indicated by the HeLa cell infection assay. Specific IgG, IgA antibody against HPV16L1 virus-like particles (VLPs) were detected in the sera,intestinal lavage and vaginal lavage from animals immunized by sh42-HPV 16L 1. The number of antibodysecreting cells in the spleen and draining lymph nodes were increased significantly compared with the control group. Sera from immunized animals inhibited murine hemagglutination induced by HPV16L1 VLPs, which indicated that the candidate vaccine could stimulate an efficient immune response in guinea pig's mucosal sites. This may be an effective strategy for the development of an HPV prophylactic oral vaccine.

  16. Salmonella enterica serovar typhimurium trxA mutants are protective against virulent challenge and induce less inflammation than the live-attenuated vaccine strain SL3261.

    Science.gov (United States)

    Peters, S E; Paterson, G K; Bandularatne, E S D; Northen, H C; Pleasance, S; Willers, C; Wang, J; Foote, A K; Constantino-Casas, F; Scase, T J; Blacklaws, B A; Bryant, C E; Mastroeni, P; Charles, I G; Maskell, D J

    2010-01-01

    In Salmonella enterica serovar Typhimurium, trxA encodes thioredoxin 1, a small, soluble protein with disulfide reductase activity, which catalyzes thiol disulfide redox reactions in a variety of substrate proteins. Thioredoxins are involved as antioxidants in defense against oxidative stresses, such as exposure to hydrogen peroxide and hydroxyl radicals. We have made a defined, complete deletion of trxA in the mouse-virulent S. Typhimurium strain SL1344 (SL1344 trxA), replacing the gene with a kanamycin resistance gene cassette. SL1344 trxA was attenuated for virulence in BALB/c mice by the oral and intravenous routes and when used in immunization experiments provided protection against challenge with the virulent parent strain. SL1344 trxA induced less inflammation in murine spleens and livers than SL3261, the aroA mutant, live attenuated vaccine strain. The reduced splenomegaly observed following infection with SL1344 trxA was partially attributed to a reduction in the number of both CD4(+) and CD8(+) T cells and B lymphocytes in the spleen and reduced infiltration by CD11b(+) cells into the spleen compared with spleens from mice infected with SL3261. This less severe pathological response indicates that a trxA mutation might be used to reduce reactogenicity of live attenuated vaccine strains. We tested this by deleting trxA in SL3261. SL3261 trxA was also less inflammatory than SL3261 but was slightly less effective as a vaccine strain than either the SL3261 parent strain or SL1344 trxA.

  17. Generation of Live Attenuated Novel Influenza Virus A/California/7/09 (H1N1) Vaccines with High Yield in Embryonated Chicken Eggs ▿

    Science.gov (United States)

    Chen, Zhongying; Wang, Weijia; Zhou, Helen; Suguitan, Amorsolo L.; Shambaugh, Cindy; Kim, Lomi; Zhao, Jackie; Kemble, George; Jin, Hong

    2010-01-01

    Several live attenuated influenza virus A/California/7/09 (H1N1) (CA09) candidate vaccine variants that possess the hemagglutinin (HA) and neuraminidase (NA) gene segments from the CA09 virus and six internal protein gene segments from the cold-adapted influenza virus A/Ann Arbor/6/60 (H2N2) virus were generated by reverse genetics. The reassortant viruses replicated relatively poorly in embryonated chicken eggs. To improve virus growth in eggs, reassortants expressing the HA and NA of CA09 were passaged in MDCK cells and variants exhibiting large-plaque morphology were isolated. These variants replicated at levels approximately 10-fold higher than the rate of replication of the parental strains in embryonated chicken eggs. Sequence analysis indicated that single amino acid changes at positions 119, 153, 154, and 186 were responsible for the improved growth properties in MDCK cells and eggs. In addition, the introduction of a mutation at residue 155 that was previously shown to enhance the replication of a 1976 swine influenza virus also significantly improved the replication of the CA09 virus in eggs. Each variant was further evaluated for receptor binding preference, antigenicity, attenuation phenotype, and immunogenicity. Mutations at residues 153, 154, and 155 drastically reduced viral antigenicity, which made these mutants unsuitable as vaccine candidates. However, changes at residues 119 and 186 did not affect virus antigenicity or immunogenicity, justifying their inclusion in live attenuated vaccine candidates to protect against the currently circulating 2009 swine origin H1N1 viruses. PMID:19864389

  18. Generation of live attenuated novel influenza virus A/California/7/09 (H1N1) vaccines with high yield in embryonated chicken eggs.

    Science.gov (United States)

    Chen, Zhongying; Wang, Weijia; Zhou, Helen; Suguitan, Amorsolo L; Shambaugh, Cindy; Kim, Lomi; Zhao, Jackie; Kemble, George; Jin, Hong

    2010-01-01

    Several live attenuated influenza virus A/California/7/09 (H1N1) (CA09) candidate vaccine variants that possess the hemagglutinin (HA) and neuraminidase (NA) gene segments from the CA09 virus and six internal protein gene segments from the cold-adapted influenza virus A/Ann Arbor/6/60 (H2N2) virus were generated by reverse genetics. The reassortant viruses replicated relatively poorly in embryonated chicken eggs. To improve virus growth in eggs, reassortants expressing the HA and NA of CA09 were passaged in MDCK cells and variants exhibiting large-plaque morphology were isolated. These variants replicated at levels approximately 10-fold higher than the rate of replication of the parental strains in embryonated chicken eggs. Sequence analysis indicated that single amino acid changes at positions 119, 153, 154, and 186 were responsible for the improved growth properties in MDCK cells and eggs. In addition, the introduction of a mutation at residue 155 that was previously shown to enhance the replication of a 1976 swine influenza virus also significantly improved the replication of the CA09 virus in eggs. Each variant was further evaluated for receptor binding preference, antigenicity, attenuation phenotype, and immunogenicity. Mutations at residues 153, 154, and 155 drastically reduced viral antigenicity, which made these mutants unsuitable as vaccine candidates. However, changes at residues 119 and 186 did not affect virus antigenicity or immunogenicity, justifying their inclusion in live attenuated vaccine candidates to protect against the currently circulating 2009 swine origin H1N1 viruses.

  19. Introduction of silent mutations into the NP gene of influenza A viruses as a possible strategy for the creation of a live attenuated vaccine.

    Science.gov (United States)

    Anhlan, Darisuren; Hrincius, Eike-Roman; Scholtissek, Christoph; Ludwig, Stephan

    2012-06-22

    The nucleoprotein (NP) of influenza A virus (IAV) is associated with many different functions including host range restriction. Multiple sequence alignment analyses of 748 NP gene sequences from GenBank revealed a highly conserved region of 60 nucleotides within the ORF at the 3'-ends of the cRNA, in some codons even silent mutations were not found. This suggests that the RNA structure integrity within this region is crucial for IAV replication. To explore the impact of these conserved nucleotides for viral replication we created mutant viruses with one or more silent mutations in the respective region of the NP gene of the IAV strain A/WSN/33 (H1N1) (WSN). Assessment of viral replication of these WSN mutant viruses showed significant growth disadvantages when compared to the corresponding parental strain. On the basis of these findings we tested whether the attenuation of IAV by introduction of silent mutations into the NP gene may serve as a strategy to create a live attenuated vaccine. Mice vaccinated with the attenuated WSN mutant survived a lethal challenge dose of wild type WSN virus or the mouse adapted pandemic H1N1v strain A/Hamburg/4/2009. Thus, introduction of silent mutations in the NP of IAV is a feasible approach for a novel vaccination strategy allowing attenuation of the master strain but leaves the antigenicity of the gene product unaltered. This principle is potentially applicable for all viruses with segmented genomes. Copyright © 2012 Elsevier Ltd. All rights reserved.

  20. Comparative sequence analysis of the P-, M- and L-coding region of the measles virus CAM-70 live attenuated vaccine strain

    Directory of Open Access Journals (Sweden)

    P.R. Santos

    2003-11-01

    Full Text Available Measles virus is a highly contagious agent which causes a major health problem in developing countries. The viral genomic RNA is single-stranded, nonsegmented and of negative polarity. Many live attenuated vaccines for measles virus have been developed using either the prototype Edmonston strain or other locally isolated measles strains. Despite the diverse geographic origins of the vaccine viruses and the different attenuation methods used, there was remarkable sequence similarity of H, F and N genes among all vaccine strains. CAM-70 is a Japanese measles attenuated vaccine strain widely used in Brazilian children and produced by Bio-Manguinhos since 1982. Previous studies have characterized this vaccine biologically and genomically. Nevertheless, only the F, H and N genes have been sequenced. In the present study we have sequenced the remaining P, M and L genes (approximately 1.6, 1.4 and 6.5 kb, respectively to complete the genomic characterization of CAM-70 and to assess the extent of genetic relationship between CAM-70 and other current vaccines. These genes were amplified using long-range or standard RT-PCR techniques, and the cDNA was cloned and automatically sequenced using the dideoxy chain-termination method. The sequence analysis comparing previously sequenced genotype A strains with the CAM-70 Bio-Manguinhos strain showed a low divergence among them. However, the CAM-70 strains (CAM-70 Bio-Manguinhos and a recently sequenced CAM-70 submaster seed strain were assigned to a specific group by phylogenetic analysis using the neighbor-joining method. Information about our product at the genomic level is important for monitoring vaccination campaigns and for future studies of measles virus attenuation.

  1. Live Cell Analysis and Mathematical Modeling Identify Determinants of Attenuation of Dengue Virus 2'-O-Methylation Mutant.

    Directory of Open Access Journals (Sweden)

    Bianca Schmid

    2015-12-01

    Full Text Available Dengue virus (DENV is the most common mosquito-transmitted virus infecting ~390 million people worldwide. In spite of this high medical relevance, neither a vaccine nor antiviral therapy is currently available. DENV elicits a strong interferon (IFN response in infected cells, but at the same time actively counteracts IFN production and signaling. Although the kinetics of activation of this innate antiviral defense and the timing of viral counteraction critically determine the magnitude of infection and thus disease, quantitative and kinetic analyses are lacking and it remains poorly understood how DENV spreads in IFN-competent cell systems. To dissect the dynamics of replication versus antiviral defense at the single cell level, we generated a fully viable reporter DENV and host cells with authentic reporters for IFN-stimulated antiviral genes. We find that IFN controls DENV infection in a kinetically determined manner that at the single cell level is highly heterogeneous and stochastic. Even at high-dose, IFN does not fully protect all cells in the culture and, therefore, viral spread occurs even in the face of antiviral protection of naïve cells by IFN. By contrast, a vaccine candidate DENV mutant, which lacks 2'-O-methylation of viral RNA is profoundly attenuated in IFN-competent cells. Through mathematical modeling of time-resolved data and validation experiments we show that the primary determinant for attenuation is the accelerated kinetics of IFN production. This rapid induction triggered by mutant DENV precedes establishment of IFN-resistance in infected cells, thus causing a massive reduction of virus production rate. In contrast, accelerated protection of naïve cells by paracrine IFN action has negligible impact. In conclusion, these results show that attenuation of the 2'-O-methylation DENV mutant is primarily determined by kinetics of autocrine IFN action on infected cells.

  2. A live-attenuated HSV-2 ICP0 virus elicits 10 to 100 times greater protection against genital herpes than a glycoprotein D subunit vaccine.

    Directory of Open Access Journals (Sweden)

    William P Halford

    Full Text Available Glycoprotein D (gD-2 is the entry receptor of herpes simplex virus 2 (HSV-2, and is the immunogen in the pharmaceutical industry's lead HSV-2 vaccine candidate. Efforts to prevent genital herpes using gD-2 subunit vaccines have been ongoing for 20 years at a cost in excess of $100 million. To date, gD-2 vaccines have yielded equivocal protection in clinical trials. Therefore, using a small animal model, we sought to determine if a live-attenuated HSV-2 ICP0⁻ virus would elicit better protection against genital herpes than a gD-2 subunit vaccine. Mice immunized with gD-2 and a potent adjuvant (alum+monophosphoryl lipid A produced high titers of gD-2 antibody. While gD-2-immunized mice possessed significant resistance to HSV-2, only 3 of 45 gD-2-immunized mice survived an overwhelming challenge of the vagina or eyes with wild-type HSV-2 (MS strain. In contrast, 114 of 115 mice immunized with a live HSV-2 ICP0⁻ virus, 0ΔNLS, survived the same HSV-2 MS challenges. Likewise, 0ΔNLS-immunized mice shed an average 125-fold less HSV-2 MS challenge virus per vagina relative to gD-2-immunized mice. In vivo imaging demonstrated that a luciferase-expressing HSV-2 challenge virus failed to establish a detectable infection in 0ΔNLS-immunized mice, whereas the same virus readily infected naïve and gD-2-immunized mice. Collectively, these results suggest that a HSV-2 vaccine might be more likely to prevent genital herpes if it contained a live-attenuated HSV-2 virus rather than a single HSV-2 protein.

  3. Use of a live attenuated Salmonella enterica serovar Typhimurium vaccine on farrow-to-finish pig farms.

    Science.gov (United States)

    De Ridder, L; Maes, D; Dewulf, J; Butaye, P; Pasmans, F; Boyen, F; Haesebrouck, F; Van der Stede, Y

    2014-11-01

    Salmonella enterica infection in pigs is economically important and poses a zoonotic risk. In this study, the efficacy of an attenuated S. enterica serovar Typhimurium strain was evaluated in three farrow-to-finish pig herds. In each herd, 120 piglets were vaccinated orally at 3 and 24 days of age, while 120 piglets served as unvaccinated controls. Faeces, ileocaecal lymph nodes and caecal contents were examined for S. Typhimurium by isolation and serum was analysed for antibodies against S. Typhimurium by ELISA. All pigs were weighed at pre-weaning and slaughter to determine daily weight gain. In vaccinated pigs prior to slaughter, significantly fewer animals excreted S. enterica, there was a significantly lower S. enterica-specific mean antibody titre and there was a significantly higher mean daily weight gain compared to unvaccinated controls. In two herds, there were significantly lower proportions of S. enterica positive ileocaecal lymph nodes and caecal contents at slaughter between the vaccinated and control groups, but this difference was not significant across all three herds. S. enterica with the same auxotrophic characteristics and genotype as the vaccine strain was isolated from several samples of faeces, ileocaecal lymph nodes and caecal contents from vaccinated pigs. These findings indicate that vaccination with an attenuated S. Typhimurium strain reduces S. enterica shedding, but the reduction is not consistent and the vaccine strain may persist in tissues. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Association of the Host Immune Response with Protection Using a Live Attenuated African Swine Fever Virus Model

    Science.gov (United States)

    Carlson, Jolene; O’Donnell, Vivian; Alfano, Marialexia; Velazquez Salinas, Lauro; Holinka, Lauren G.; Krug, Peter W.; Gladue, Douglas P.; Higgs, Stephen; Borca, Manuel V.

    2016-01-01

    African swine fever (ASF) is a lethal hemorrhagic disease of swine caused by a double-stranded DNA virus, ASF virus (ASFV). There is no vaccine to prevent the disease and current control measures are limited to culling and restricting animal movement. Swine infected with attenuated strains are protected against challenge with a homologous virulent virus, but there is limited knowledge of the host immune mechanisms generating that protection. Swine infected with Pretoriuskop/96/4 (Pret4) virus develop a fatal severe disease, while a derivative strain lacking virulence-associated gene 9GL (Pret4Δ9GL virus) is completely attenuated. Swine infected with Pret4Δ9GL virus and challenged with the virulent parental virus at 7, 10, 14, 21, and 28 days post infection (dpi) showed a progressive acquisition of protection (from 40% at 7 dpi to 80% at 21 and 28 dpi). This animal model was used to associate the presence of host immune response (ASFV-specific antibody and interferon (IFN)-γ responses, or specific cytokine profiles) and protection against challenge. With the exception of ASFV-specific antibodies in survivors challenged at 21 and 28 dpi, no association between the parameters assessed and protection could be established. These results, encompassing data from 65 immunized swine, underscore the complexity of the system under study, suggesting that protection relies on the concurrence of different host immune mechanisms. PMID:27782090

  5. Association of the Host Immune Response with Protection Using a Live Attenuated African Swine Fever Virus Model

    Directory of Open Access Journals (Sweden)

    Jolene Carlson

    2016-10-01

    Full Text Available African swine fever (ASF is a lethal hemorrhagic disease of swine caused by a double-stranded DNA virus, ASF virus (ASFV. There is no vaccine to prevent the disease and current control measures are limited to culling and restricting animal movement. Swine infected with attenuated strains are protected against challenge with a homologous virulent virus, but there is limited knowledge of the host immune mechanisms generating that protection. Swine infected with Pretoriuskop/96/4 (Pret4 virus develop a fatal severe disease, while a derivative strain lacking virulence-associated gene 9GL (Pret4Δ9GL virus is completely attenuated. Swine infected with Pret4Δ9GL virus and challenged with the virulent parental virus at 7, 10, 14, 21, and 28 days post infection (dpi showed a progressive acquisition of protection (from 40% at 7 dpi to 80% at 21 and 28 dpi. This animal model was used to associate the presence of host immune response (ASFV-specific antibody and interferon (IFN-γ responses, or specific cytokine profiles and protection against challenge. With the exception of ASFV-specific antibodies in survivors challenged at 21 and 28 dpi, no association between the parameters assessed and protection could be established. These results, encompassing data from 65 immunized swine, underscore the complexity of the system under study, suggesting that protection relies on the concurrence of different host immune mechanisms.

  6. Dengue type 4 live-attenuated vaccine viruses passaged in vero cells affect genetic stability and dengue-induced hemorrhaging in mice.

    Directory of Open Access Journals (Sweden)

    Hsiang-Chi Lee

    Full Text Available Most live-attenuated tetravalent dengue virus vaccines in current clinical trials are produced from Vero cells. In a previous study we demonstrated that an infectious cDNA clone-derived dengue type 4 (DEN-4 virus retains higher genetic stability in MRC-5 cells than in Vero cells. For this study we investigated two DEN-4 viruses: the infectious cDNA clone-derived DEN-4 2A and its derived 3' NCR 30-nucleotide deletion mutant DEN-4 2AΔ30, a vaccine candidate. Mutations in the C-prM-E, NS2B-NS3, and NS4B-NS5 regions of the DEN genome were sequenced and compared following cell passages in Vero and MRC-5 cells. Our results indicate stronger genetic stability in both viruses following MRC-5 cell passages, leading to significantly lower RNA polymerase error rates when the DEN-4 virus is used for genome replication. Although no significant increases in virus titers were observed following cell passages, DEN-4 2A and DEN-4 2AΔ30 virus titers following Vero cell passages were 17-fold to 25-fold higher than titers following MRC-5 cell passages. Neurovirulence for DEN-4 2A and DEN-4 2AΔ30 viruses increased significantly following passages in Vero cells compared to passages in MRC-5 cells. In addition, more severe DEN-induced hemorrhaging in mice was noted following DEN-4 2A and DEN-4 2AΔ30 passages in Vero cells compared to passages in MRC-5 cells. Target mutagenesis performed on the DEN-4 2A infectious clone indicated that single point mutation of E-Q(438H, E-V(463L, NS2B-Q(78H, and NS2B-A(113T imperatively increased mouse hemorrhaging severity. The relationship between amino acid mutations acquired during Vero cell passage and enhanced DEN-induced hemorrhages in mice may be important for understanding DHF pathogenesis, as well as for the development of live-attenuated dengue vaccines. Taken together, the genetic stability, virus yield, and DEN-induced hemorrhaging all require further investigation in the context of live-attenuated DEN vaccine

  7. Mumps Virus: Modification of the Identify-Isolate-Inform Tool for Frontline Healthcare Providers

    Directory of Open Access Journals (Sweden)

    Kristi L. Koenig

    2016-09-01

    Full Text Available Mumps is a highly contagious viral infection that became rare in most industrialized countries following the introduction of measles-mumps-rubella (MMR vaccine in 1967. The disease, however, has been re-emerging with several outbreaks over the past decade. Many clinicians have never seen a case of mumps. To assist frontline healthcare providers with detecting potential cases and initiating critical actions, investigators modified the “Identify-Isolate-Inform” tool for mumps infection. The tool is applicable to regions with rare incidences or local outbreaks, especially seen in college students, as well as globally in areas where vaccination is less common. Mumps begins with a prodrome of low-grade fever, myalgias and malaise/anorexia, followed by development of nonsuppurative parotitis, which is the pathognomonic finding associated with acute mumps infection. Orchitis and meningitis are the two most common serious complications, with hearing loss and infertility occurring rarely. Providers should consider mumps in patients with exposure to a known case or international travel to endemic regions who present with consistent signs and symptoms. If mumps is suspected, healthcare providers must immediately implement standard and droplet precautions and notify the local health department and hospital infection control personnel.

  8. A comparison of LISP and MUMPS as implementation languages for knowledge-based systems.

    Science.gov (United States)

    Curtis, A C

    1984-10-01

    Major components of knowledge-based systems are summarized, along with the programming language features generally useful in their implementation. LISP and MUMPS are briefly described and compared as vehicles for building knowledge-based systems. The paper concludes with suggestions for extensions to MUMPS that might increase its usefulness in artificial intelligence applications without affecting the essential nature of the language.

  9. 口服轮状病毒疫苗及其保护效果%Oral live attenuated rotavirus vaccines and their protective efficacy

    Institute of Scientific and Technical Information of China (English)

    何泗涛

    2011-01-01

    Human rotavirus is the most common pathogen of childhood diarrhea,and vaccination is an effective way to reduce the morbidity of rotavirus diseases.This review briefly introduces the epidemiological and clinical characteristics of rotavirus diseases,and summarizes the protection efficacy of oral live attenuated rotavirus vaccines.%人轮状病毒是引起婴幼儿腹泻最常见的病原体,疫苗接种是降低轮状病毒疾病发病率的有效方法.此文简要介绍了轮状病毒疾病的流行病学和临床特征,并对口服轮状病毒减毒活疫苗的保护效果做一综述.

  10. Major histocompatibility complex-linked immune response of young chickens vaccinated with an attenuated live infectious bursal disease virus vaccine followed by an infection

    DEFF Research Database (Denmark)

    Juul-Madsen, Helle; Nielsen, O.L.; Krogh-Maibom, T.

    2002-01-01

    The influence of the MHC on infectious bursal disease virus (IBDV) vaccine response in chickens was investigated in three different chicken lines containing four different MHC haplotypes. Two MHC haplotypes were present in all three lines with one haplotype (1319) shared between the lines. Line I...... further contains the BW1 haplotype isolated from a Red jungle Fowl. Line 131 further contains the B131 haplotype isolated from a meat-type chicken, Finally, Line 21 further contains the international B21 haplotype. The chickens were vaccinated with live attenuated commercial IBDV vaccine at 3 wk of age...... (mean 5,243), B21 (5,570), and B131 (5,333) at 8 d postinfection, How-ever, a virus-neutralizing antibody test did not reflect this result. Nevertheless, the MHC haplotype-associated protective immunity was further supported by the bursa of Fabricius (bursa) recovery from the disease, as measured...

  11. Safety and immunogenicity of a mutagenized, live attenuated Rift Valley fever vaccine, MP-12, in a Phase 1 dose escalation and route comparison study in humans.

    Science.gov (United States)

    Pittman, Phillip R; McClain, David; Quinn, Xiaofei; Coonan, Kevin M; Mangiafico, Joseph; Makuch, Richard S; Morrill, John; Peters, Clarence J

    2016-01-20

    Rift Valley fever (RVF) poses a risk as a potential agent in bioterrorism or agroterrorism. A live attenuated RVF vaccine (RVF MP-12) has been shown to be safe and protective in animals and showed promise in two initial clinical trials. In the present study, healthy adult human volunteers (N=56) received a single injection of (a) RVF MP-12, administered subcutaneously (SQ) at a concentration of 10(4.7) plaque-forming units (pfu) (SQ Group); (b) RVF MP-12, administered intramuscularly (IM) at 10(3.4)pfu (IM Group 1); (c) RVF MP-12, administered IM at 10(4.4)pfu (IM Group 2); or (d) saline (Placebo Group). The vaccine was well tolerated by volunteers in all dose and route groups. Infrequent and minor adverse events were seen among recipients of both placebo and RVF MP-12. One subject had viremia detectable by direct plaque assay, and six subjects from IM Group 2 had transient low-titer viremia detectable only by nucleic acid amplification. Of the 43 vaccine recipients, 40 (93%) achieved neutralizing antibodies (measured as an 80% plaque reduction neutralization titer [PRNT80]) as well as RVF-specific IgM and IgG. The highest peak geometric mean PRNT80 titers were observed in IM Group 2. Of 34 RVF MP-12 recipients available for testing 1 year following inoculation, 28 (82%) remained seropositive (PRNT80≥1:20); this included 20 of 23 vaccinees (87%) from IM Group 2. The live attenuated RVF MP-12 vaccine was safe and immunogenic at the doses and routes studied. Given the need for an effective vaccine against RVF virus, further evaluation in humans is warranted.

  12. A live attenuated Salmonella Enteritidis secreting detoxified heat labile toxin enhances mucosal immunity and confers protection against wild-type challenge in chickens.

    Science.gov (United States)

    Lalsiamthara, Jonathan; Kamble, Nitin Machindra; Lee, John Hwa

    2016-06-04

    A live attenuated Salmonella Enteritidis (SE) capable of constitutively secreting detoxified double mutant Escherichia coli heat labile toxin (dmLT) was developed. The biologically adjuvanted strain was generated via transformation of a highly immunogenic SE JOL1087 with a plasmid encoding dmLT gene cassette; the resultant strain was designated JOL1641. A balanced-lethal host-vector system stably maintained the plasmid via auxotrophic host complementation with a plasmid encoded aspartate semialdehyde dehydrogenase (asd) gene. Characterization by western blot assay revealed the dmLT subunit proteins in culture supernatants of JOL1641. For the investigation of adjuvanticity and protective efficacy, chickens were immunized via oral or intramuscular routes with PBS, JOL1087 and JOL1641. Birds immunized with JOL1641 showed significant (P ≤ 0.05) increases in intestinal SIgA production at the 1(st) and 2(nd) weeks post-immunization via oral and intramuscular routes, respectively. Interestingly, while both strains showed significant splenic protection via intramuscular immunization, JOL1641 outperformed JOL1087 upon oral immunization. Oral immunization of birds with JOL1641 significantly reduced splenic bacterial counts. The reduction in bacterial counts may be correlated with an adjuvant effect of dmLT that increases SIgA secretion in the intestines of immunized birds. The inclusion of detoxified dmLT in the strain did not cause adverse reactions to birds, nor did it extend the period of bacterial fecal shedding. In conclusion, we report here that dmLT could be biologically incorporated in the secretion system of a live attenuated Salmonella-based vaccine, and that this construction is safe and could enhance mucosal immunity, and protect immunized birds against wild-type challenge.

  13. Evaluating the effectiveness, impact and safety of live attenuated and seasonal inactivated influenza vaccination: protocol for the Seasonal Influenza Vaccination Effectiveness II (SIVE II) study

    Science.gov (United States)

    Lone, Nazir I; Kavanagh, Kimberley; Robertson, Chris; McMenamin, Jim; von Wissmann, Beatrix; Vasileiou, Eleftheria; Butler, Chris; Ritchie, Lewis D; Gunson, Rory; Schwarze, Jürgen; Sheikh, Aziz

    2017-01-01

    Introduction Seasonal (inactivated) influenza vaccination is recommended for all individuals aged 65+ and in individuals under 65 who are at an increased risk of complications of influenza infection, for example, people with asthma. Live attenuated influenza vaccine (LAIV) was recommended for children as they are thought to be responsible for much of the transmission of influenza to the populations at risk of serious complications from influenza. A phased roll-out of the LAIV pilot programme began in 2013/2014. There is limited evidence for vaccine effectiveness (VE) in the populations targeted for influenza vaccination. The aim of this study is to examine the safety and effectiveness of the live attenuated seasonal influenza vaccine programme in children and the inactivated seasonal influenza vaccination programme among different age and at-risk groups of people. Methods and analysis Test negative and cohort study designs will be used to estimate VE. A primary care database covering 1.25 million people in Scotland for the period 2000/2001 to 2015/2016 will be linked to the Scottish Immunisation Recall Service (SIRS), Health Protection Scotland virology database, admissions to Scottish hospitals and the Scottish death register. Vaccination status (including LAIV uptake) will be determined from the primary care and SIRS database. The primary outcome will be influenza-positive real-time PCR tests carried out in sentinel general practices and other healthcare settings. Secondary outcomes include influenza-like illness and asthma-related general practice consultations, hospitalisations and death. An instrumental variable analysis will be carried out to account for confounding. Self-controlled study designs will be used to estimate the risk of adverse events associated with influenza vaccination. Ethics and dissemination We obtained approval from the National Research Ethics Service Committee, West Midlands—Edgbaston. The study findings will be presented at

  14. LcrV delivered via type III secretion system of live attenuated Yersinia pseudotuberculosis enhances immunogenicity against pneumonic plague.

    Science.gov (United States)

    Sun, Wei; Sanapala, Shilpa; Henderson, Jeremy C; Sam, Shandiin; Olinzock, Joseph; Trent, M Stephen; Curtiss, Roy

    2014-10-01

    Here, we constructed a Yersinia pseudotuberculosis mutant strain with arabinose-dependent regulated and delayed shutoff of crp expression (araC P(BAD) crp) and replacement of the msbB gene with the Escherichia coli msbB gene to attenuate it. Then, we inserted the asd mutation into this construction to form χ10057 [Δasd-206 ΔmsbB868::P(msbB) msbB(EC) ΔP(crp21)::TT araC P(BAD) crp] for use with a balanced-lethal Asd-positive (Asd(+)) plasmid to facilitate antigen synthesis. A hybrid protein composed of YopE (amino acids [aa]1 to 138) fused with full-length LcrV (YopE(Nt138)-LcrV) was synthesized in χ10057 harboring an Asd(+) plasmid (pYA5199, yopE(Nt138)-lcrV) and could be secreted through a type III secretion system (T3SS) in vitro and in vivo. Animal studies indicated that mice orally immunized with χ10057(pYA5199) developed titers of IgG response to whole-cell lysates of Y. pestis (YpL) and subunit LcrV similar to those seen with χ10057(pYA3332) (χ10057 plus an empty plasmid). However, only immunization of mice with χ10057(pYA5199) resulted in a significant secretory IgA response to LcrV. χ10057(pYA5199) induced a higher level of protection (80% survival) against intranasal (i.n.) challenge with ~240 median lethal doses (LD50) (2.4 × 10(4) CFU) of Y. pestis KIM6+(pCD1Ap) than χ10057(pYA3332) (40% survival). Splenocytes from mice vaccinated with χ10057(pYA5199) produced significant levels of gamma interferon (IFN-γ), tumor necrosis factor alpha (TNF-α), and interleukin-17 (IL-17) after restimulation with LcrV and YpL antigens. Our results suggest that it is possible to use an attenuated Y. pseudotuberculosis strain delivering the LcrV antigen via the T3SS as a potential vaccine candidate against pneumonic plague.

  15. CD8 Knockout Mice Are Protected from Challenge by Vaccination with WR201, a Live Attenuated Mutant of Brucella melitensis

    Directory of Open Access Journals (Sweden)

    Samuel L. Yingst

    2013-01-01

    Full Text Available CD8+ T cells have been reported to play an important role in defense against B. abortus infection in mouse models. In the present report, we use CD8 knockout mice to further elucidate the role of these cells in protection from B. melitensis infection. Mice were immunized orally by administration of B. melitensis WR201, a purine auxotrophic attenuated vaccine strain, then challenged intranasally with B. melitensis 16M. In some experiments, persistence of WR201 in the spleens of CD8 knockout mice was slightly longer than that in the spleens of normal mice. However, development of anti-LPS serum antibody, antigen-induced production of γ-interferon (IFN-γ by immune splenic lymphocytes, protection against intranasal challenge, and recovery of nonimmunized animals from intranasal challenge were similar between normal and knockout animals. Further, primary Brucella infection was not exacerbated in perforin knockout and Fas-deficient mice and these animals’ anti-Brucella immune responses were indistinguishable from those of normal mice. These results indicate that CD8+ T cells do not play an essential role as either cytotoxic cells or IFN-γ producers, yet they do participate in a specific immune response to immunization and challenge in this murine model of B. melitensis infection.

  16. Limited potential for mosquito transmission of genetically engineered, live-attenuated western equine encephalitis virus vaccine candidates.

    Science.gov (United States)

    Turell, Michael J; O'Guinn, Monica L; Parker, Michael D

    2003-02-01

    Specific mutations associated with attenuation of Venezuelan equine encephalitis (VEE) virus in rodent models were identified during efforts to develop an improved VEE vaccine. Analogous mutations were produced in full-length cDNA clones of the Cba 87 strain of western equine encephalitis (WEE) virus by site-directed mutagenesis in an attempt to develop an improved WEE vaccine. Isogenic viral strains with these mutations were recovered after transfection of baby hamster kidney cells with infectious RNA. We evaluated two of these strains (WE2102 and WE2130) for their ability to replicate in and be transmitted by Culex tarsalis, the principal natural vector of WEE virus in the United States. Each of the vaccine candidates contained a deletion of the PE2 furin cleavage site and a secondary mutation in the E1 or E2 glycoprotein. Both of these potential candidates replicated in mosquitoes significantly less efficiently than did either wild-type WEE (Cba 87) virus or the parental clone (WE2000). Likewise, after intrathoracic inoculation, mosquitoes transmitted the vaccine candidate strains significantly less efficiently than they transmitted either the wild-type or the parental clone. One-day-old chickens vaccinated with either of the two vaccine candidates did not become viremic when challenged with virulent WEE virus two weeks later. Mutations that result in less efficient replication in or transmission by mosquitoes should enhance vaccine safety and reduce the possibility of accidental introduction of the vaccine strain to unintentional hosts.

  17. Analysis of serum th1/th2 cytokine levels in patients with acute mumps infection

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    Jeevan Malaiyan

    2016-01-01

    Full Text Available Background: The mumps virus is frequently the causative agent of parotitis. There has been no study on serum cytokine levels of acute mumps parotitis except for a few which document cytokine levels in cerebrospinal fluid of mumps meningitis. It is with this notion, our study aimed to find Th1/Th2 cytokine levels from patients with acute mumps parotitis. Materials and Methods: Concentrations of mumps-specific IgM, mumps, measles, rubella-specific IgG antibody, and Th1/Th2 cytokines, namely interferon-g (IFN-g, interleukin-2 (IL-2, IL-4, and IL-10 were measured simultaneously in serum from 74 patients (42 pediatric and 32 adult cases, 40 healthy subjects (20 pediatric and 20 adults and in the supernatant of peripheral blood mononuclear cells stimulated with mumps virus genotype C which served as the positive control. Statistical significance was analyzed between each group by means of Mann-Whitney U-test, Kruskal-Wallis test, and Spearman′s rank correlation coefficient test. Results: IgM positivity confirmed acute infection in all 74 patients and of these 67 were vaccinated cases; however, very few of them (10/67 were positive for mumps IgG. We found that IFN-g, IL-2, and IL-10 showed a statistically significant increase in both pediatric and adult patients with acute mumps infection when compared to healthy controls and values were comparable to the positive control. Conclusion: The Th1 cells play important roles during the acute phase of mumps parotitis.

  18. Three amino acid substitutions in the L protein of the human parainfluenza virus type 3 cp45 live attenuated vaccine candidate contribute to its temperature-sensitive and attenuation phenotypes.

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    Skiadopoulos, M H; Durbin, A P; Tatem, J M; Wu, S L; Paschalis, M; Tao, T; Collins, P L; Murphy, B R

    1998-03-01

    Studies were initiated to define the genetic basis of the temperature-sensitive (ts), cold adaptation (ca), and attenuation (att) phenotypes of the human parainfluenza virus type 3 (PIV3) cp45 live attenuated vaccine candidate. Genetic data had previously suggested that the L polymerase protein of cp45, which contains three amino acid substitutions at positions 942, 992, and 1558, contributed to its temperature sensitivity (R. Ray, M. S. Galinski, B. R. Heminway, K. Meyer, F. K. Newman, and R. B. Belshe, J. Virol. 70:580-584, 1996; A. Stokes, E. L. Tierney, C. M. Sarris, B. R. Murphy, and S. L. Hall, Virus Res. 30:43-52, 1993). To study the individual and aggregate contributions that these amino acid substitutions make to the ts, att, and ca phenotypes of cp45, seven PIV3 recombinant viruses (three single, three double, and one triple mutant) representing all possible combinations of the three amino acid substitutions were recovered from full-length antigenomic cDNA and analyzed for their ts, att, and ca phenotypes. None of the seven mutant recombinant PIVs was cold adapted. The substitutions at L protein amino acid positions 992 and 1558 each specified a 105-fold reduction in plaque formation in cell culture at 40 degrees C, whereas the substitution at position 942 specified a 300-fold reduction. Thus, each of the three mutations contributes individually to the ts phenotype. The triple recombinant which possesses an L protein with all three mutations was almost as temperature sensitive as cp45, indicating that these mutations are the major contributors to the ts phenotype of cp45. The three individual mutations in the L protein each contributed to restricted replication in the upper or lower respiratory tract of hamsters, and this likely contributes to the observed stability of the ts and att phenotypes of cp45 during replication in vivo. Importantly, the recombinant virus possessing L protein with all three mutations was as restricted in replication as was the cp

  19. Refined live attenuated Salmonella enterica serovar Typhimurium and Enteritidis vaccines mediate homologous and heterologous serogroup protection in mice.

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    Tennant, Sharon M; Schmidlein, Patrick; Simon, Raphael; Pasetti, Marcela F; Galen, James E; Levine, Myron M

    2015-12-01

    Invasive nontyphoidal Salmonella (NTS) infections constitute a major health problem among infants and toddlers in sub-Saharan Africa; these infections also occur in infants and the elderly in developed countries. We genetically engineered a Salmonella enterica serovar Typhimurium strain of multilocus sequence type 313, the predominant genotype circulating in sub-Saharan Africa. We evaluated the capacities of S. Typhimurium and Salmonella enterica serovar Enteritidis ΔguaBA ΔclpX live oral vaccines to protect mice against a highly lethal challenge dose of the homologous serovar and determined protection against other group B and D serovars circulating in sub-Saharan Africa. The vaccines S. Typhimurium CVD 1931 and S. Enteritidis CVD 1944 were immunogenic and protected BALB/c mice against 10,000 50% lethal doses (LD50) of S. Typhimurium or S. Enteritidis, respectively. S. Typhimurium CVD 1931 protected mice against the group B serovar Salmonella enterica serovar Stanleyville (91% vaccine efficacy), and S. Enteritidis CVD 1944 protected mice against the group D serovar Salmonella enterica serovar Dublin (85% vaccine efficacy). High rates of survival were observed when mice were infected 12 weeks postimmunization, indicating that the vaccines elicited long-lived protective immunity. Whereas CVD 1931 did not protect against S. Enteritidis R11, CVD 1944 did mediate protection against S. Typhimurium D65 (81% efficacy). These findings suggest that a bivalent (S. Typhimurium and S. Enteritidis) vaccine would provide broad protection against the majority of invasive NTS infections in sub-Saharan Africa.

  20. Frequency of lymphocytic meningitis associated with mumps before and after a mass campaign for mumps vaccination in children from Salvador, Northeast Brazil

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    Nascimento-Carvalho Cristiana M.

    2003-01-01

    Full Text Available OBJECTIVE: To describe the frequency of lymphocytic meningitis(LM concomitant with mumps, before and after the mumps mass immunization campaign in 1997. METHOD: Demographic, clinical and cerebrospinal fluid(CSF information was collected from the chart of all patients aged from 2 to 59 months, whose CSF exam was performed at the CSF Lab/FJS, between 1989 and 2001. LM was defined as pleocytosis composed by lymphomononuclear cells and negative exams for bacterial or mycologic infection. RESULTS: Of 1,519 patients, 894(58.9% had normal exams. LM was present in 301(19.8% patients, out of which 22(7.3% had concomitant mumps. The frequency of LM ranged from 15.8% in 1989 to 19.7% in 2001 and of LM with concomitant Mumps ranged from 10.5% in 1989 to 4.7% in 1995, when the last cases were registered. CONCLUSION: It is probable that the mumps vaccine campaign has influenced the absence of LM with concomitant Mumps, from 1996 to 2001.

  1. Use of mchI Encoding Immunity to the Antimicrobial Peptide Microcin H47 as a Plasmid Selection Marker in Attenuated Bacterial Live Vectors▿

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    Fang, Chee-Mun; Wang, Jin Yuan; Chinchilla, Magaly; Levine, Myron M.; Blackwelder, William C.; Galen, James E.

    2008-01-01

    Live attenuated bacterial strains expressing heterologous antigens represent an attractive vaccine development strategy. However, the use of drug resistance genes for the selection of expression plasmids introduced into live vectors poses theoretical health risks. Therefore, we developed a novel approach for plasmid selection based on immunity to the antimicrobial peptide microcin H47 (MccH47). Two expression plasmids encoding the reporter green fluorescent protein (GFPuv) were constructed; selection markers comprised either mchI, conferring immunity to MccH47 (pGEN222I), or bla (encoding β-lactamase), conferring conventional resistance to ampicillin (pGEN222). GFPuv-specific serum immunoglobulin G (IgG) antibody responses were analyzed in mice immunized intranasally either with Salmonella enterica serovar Typhi CVD 908-htrA or Shigella flexneri 2a CVD 1208S live vector and were boosted parenterally with purified GFPuv. Similar IgG antibody responses were observed for both pGEN222 and pGEN222I when either CVD 1208S or CVD 908-htrA(pGEN222I) was used as the carrier. Interestingly, CVD 908-htrA(pGEN222I) elicited a significantly higher IgG response than CVD 908-htrA(pGEN222). We also compared the priming potential of homologous priming either with CVD 908-htrA(pGEN222I) or CVD 1208S(pGEN222I) to heterologous priming first with CVD 908-htrA(pGEN222I) and then with CVD 1208S(pGEN222I) and vice versa. Immunization with two unrelated live vectors significantly enhanced the IgG responses compared to responses engendered by homologous CVD 908-htrA(pGEN222I) but not to those of CVD 1208S(pGEN222I). MccH47 offers an alternate system for plasmid selection in bacterial live vectors that greatly improves their clinical acceptability. Furthermore, the success of the heterologous priming strategy supports the feasibility of the future development of multivalent live vector-based immunization strategies against multiple human pathogens. PMID:18663003

  2. Long-Lived αMUPA Mice Show Attenuation of Cardiac Aging and Leptin-Dependent Cardioprotection.

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    Esther Levy

    Full Text Available αMUPA transgenic mice spontaneously consume less food compared with their wild type (WT ancestors due to endogenously increased levels of the satiety hormone leptin. αMUPA mice share many benefits with mice under caloric restriction (CR including an extended life span. To understand mechanisms linked to cardiac aging, we explored the response of αMUPA hearts to ischemic conditions at the age of 6, 18, or 24 months. Mice were subjected to myocardial infarction (MI in vivo and to ischemia/reperfusion ex vivo. Compared to WT mice, αMUPA showed functional and histological advantages under all experimental conditions. At 24 months, none of the WT mice survived the first ischemic day while αMUPA mice demonstrated 50% survival after 7 ischemic days. Leptin, an adipokine decreasing under CR, was consistently ~60% higher in αMUPA sera at baseline. Leptin levels gradually increased in both genotypes 24h post MI but were doubled in αMUPA. Pretreatment with leptin neutralizing antibodies or with inhibitors of leptin signaling (AG-490 and Wortmannin abrogated the αMUPA benefits. The antibodies also reduced phosphorylation of the leptin signaling components STAT3 and AKT specifically in the αMUPA myocardium. αMUPA mice did not show elevation in adiponectin, an adipokine previously implicated in CR-induced cardioprotection. WT mice treated for short-term CR exhibited cardioprotection similar to that of αMUPA, however, along with increased adiponectin at baseline. Collectively, the results demonstrate a life-long increased ischemic tolerance in αMUPA mice, indicating the attenuation of cardiac aging. αMUPA cardioprotection is mediated through endogenous leptin, suggesting a protective pathway distinct from that elicited under CR.

  3. Peru-15 (Choleragarde(®)), a live attenuated oral cholera vaccine, is safe and immunogenic in human immunodeficiency virus (HIV)-seropositive adults in Thailand.

    Science.gov (United States)

    Ratanasuwan, W; Kim, Y H; Sah, B K; Suwanagool, S; Kim, D R; Anekthananon, A; Lopez, A L; Techasathit, W; Grahek, S L; Clemens, J D; Wierzba, T F

    2015-09-11

    Many areas with endemic and epidemic cholera report significant levels of HIV transmission. According to the World Health Organization (WHO), over 95% of reported cholera cases occur in Africa, which also accounts for nearly 70% of people living with HIV/AIDS globally. Peru-15, a promising single dose live attenuated oral cholera vaccine (LA-OCV), was previously found to be safe and immunogenic in cholera endemic areas. However, no data on the vaccine's safety among HIV-seropositive adults had been collected. This study was a double-blinded, individually randomized, placebo-controlled trial enrolling HIV-seropositive adults, 18-45 years of age, conducted in Bangkok, Thailand, to assess the safety of Peru-15 in a HIV-seropositive cohort. 32 HIV infected subjects were randomized to receive either a single oral dose of the Peru-15 vaccine with a buffer or a placebo (buffer only). No serious adverse events were reported during the follow-up period in either group. The geometric mean fold (GMF) rise in V. cholerae O1 El Tor specific antibody titers between baseline and 7 days after dosing was 32.0 (pvaccine group compared to 1.6 (pvaccine strain. There were no significant changes in HIV viral load or CD4 T-cell counts between vaccine and placebo groups. Peru-15 was shown to be safe and immunogenic in HIV-seropositive Thai adults. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Vaccination of pigs against Aujeszky's disease by the intradermal route using live attenuated and inactivated virus vaccines.

    Science.gov (United States)

    Vannier, P; Cariolet, R

    1989-09-01

    A study was undertaken of the protection induced by inactivated and live Aujeszky's disease virus vaccines. The vaccines were administered using a special device which, without the use of a needle, delivered the preparation intradermally. The trials were performed on 88 pigs which were vaccinated at the beginning of the fattening period both in experimental conditions and in pig herds. All the pigs were challenged at the end of the fattening period in isolation units. The results obtained were compared with those obtained using the same vaccines injected intramuscularly. It was shown that vaccination via the intradermal route induced good protection in the vaccinated animals and was similar to that conferred by live virus vaccine injected intramuscularly. The results, with the inactivated virus vaccine, were not so good when it was injected via the intradermal route. Studies with intradermal vaccination showed no local lesion or very small nodules strictly localized to the dermis. The results also confirmed that the effects of challenge exposure depended on the health status of animals prior to infection and show the necessity to use a synthetic value (delta G) to interpret the data and mainly to compare the results objectively. In fattening pigs this vaccination procedure is attractive because (i) less animal constraint is needed than would be for intramuscular injections, (ii) injection can be checked by the presence of a visible papula at the site of inoculation and, (iii) pigs can be vaccinated in the ham while they are feeding. Injection without a needle also contributes to avoiding bacterial contamination under practical farm conditions of vaccination.

  5. Single HA2 mutation increases the infectivity and immunogenicity of a live attenuated H5N1 intranasal influenza vaccine candidate lacking NS1.

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    Brigitte M Krenn

    Full Text Available BACKGROUND: H5N1 influenza vaccines, including live intranasal, appear to be relatively less immunogenic compared to seasonal analogs. The main influenza virus surface glycoprotein hemagglutinin (HA of highly pathogenic avian influenza viruses (HPAIV was shown to be more susceptible to acidic pH treatment than that of human or low pathogenic avian influenza viruses. The acidification machinery of the human nasal passageway in response to different irritation factors starts to release protons acidifying the mucosal surface (down to pH of 5.2. We hypothesized that the sensitivity of H5 HA to the acidic environment might be the reason for the low infectivity and immunogenicity of intranasal H5N1 vaccines for mammals. METHODOLOGY/PRINCIPAL FINDINGS: We demonstrate that original human influenza viruses infect primary human nasal epithelial cells at acidic pH (down to 5.4, whereas H5N1 HPAIVs lose infectivity at pH ≤ 5.6. The HA of A/Vietnam/1203/04 was modified by introducing the single substitution HA2 58K→I, decreasing the pH of the HA conformational change. The H5N1 reassortants containing the indicated mutation displayed an increased resistance to acidic pH and high temperature treatment compared to those lacking modification. The mutation ensured a higher viral uptake as shown by immunohistochemistry in the respiratory tract of mice and 25 times lower mouse infectious dose₅₀. Moreover, the reassortants keeping 58K→I mutation designed as a live attenuated vaccine candidate lacking an NS1 gene induced superior systemic and local antibody response after the intranasal immunization of mice. CONCLUSION/SIGNIFICANCE: Our finding suggests that an efficient intranasal vaccination with a live attenuated H5N1 virus may require a certain level of pH and temperature stability of HA in order to achieve an optimal virus uptake by the nasal epithelial cells and induce a sufficient immune response. The pH of the activation of the H5 HA protein may

  6. Immunogenicity of viral vector, prime-boost SIV vaccine regimens in infant rhesus macaques: attenuated vesicular stomatitis virus (VSV) and modified vaccinia Ankara (MVA) recombinant SIV vaccines compared to live-attenuated SIV.

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    Van Rompay, Koen K A; Abel, Kristina; Earl, Patricia; Kozlowski, Pamela A; Easlick, Juliet; Moore, Joseph; Buonocore-Buzzelli, Linda; Schmidt, Kimberli A; Wilson, Robert L; Simon, Ian; Moss, Bernard; Rose, Nina; Rose, John; Marthas, Marta L

    2010-02-10

    In a previously developed infant macaque model mimicking HIV infection by breast-feeding, we demonstrated that intramuscular immunization with recombinant poxvirus vaccines expressing simian immunodeficiency virus (SIV) structural proteins provided partial protection against infection following oral inoculation with virulent SIV. In an attempt to further increase systemic but also local antiviral immune responses at the site of viral entry, we tested the immunogenicity of different orally administered, replicating vaccines. One group of newborn macaques received an oral prime immunization with a recombinant vesicular stomatitis virus expressing SIVmac239 gag, pol and env (VSV-SIVgpe), followed 2 weeks later by an intramuscular boost immunization with MVA-SIV. Another group received two immunizations with live-attenuated SIVmac1A11, administered each time both orally and intravenously. Control animals received mock immunizations or non-SIV VSV and MVA control vectors. Analysis of SIV-specific immune responses in blood and lymphoid tissues at 4 weeks of age demonstrated that both vaccine regimens induced systemic antibody responses and both systemic and local cell-mediated immune responses. The safety and immunogenicity of the VSV-SIVgpe+MVA-SIV immunization regimen described in this report provide the scientific incentive to explore the efficacy of this vaccine regimen against virulent SIV exposure in the infant macaque model.

  7. Evaluation of live-attenuated Salmonella vaccines expressing Campylobacter antigens for control of C. jejuni in poultry.

    Science.gov (United States)

    Buckley, Anthony M; Wang, Jinhong; Hudson, Debra L; Grant, Andrew J; Jones, Michael A; Maskell, Duncan J; Stevens, Mark P

    2010-01-22

    Campylobacter jejuni is a zoonotic bacterial pathogen of worldwide importance. It is estimated that 460,000 human infections occur in the United Kingdom per annum and these involve acute enteritis and may be complicated by severe systemic sequelae. Such infections are frequently associated with the consumption of contaminated poultry meat and strategies to control C. jejuni in poultry are expected to limit pathogen entry into the food chain and the incidence of human disease. Toward this aim, a total of 840 Light Sussex chickens were used to evaluate a Salmonella enterica serovar Typhimurium DeltaaroA vaccine expressing the C. jejuni amino acid binding protein CjaA as a plasmid-borne fusion to the C-terminus of fragment C of tetanus toxin. Chickens were given the vaccine at 1-day-old and two weeks later by oral gavage, then challenged after a further two weeks with C. jejuni. Across six biological replicates, statistically significant reductions in caecal C. jejuni of c. 1.4log(10) colony-forming units/g were observed at three and four weeks post-challenge relative to age-matched unvaccinated birds. Protection was associated with the induction of CjaA-specific serum IgY and biliary IgA. Protection was not observed using a vaccine strain containing the empty plasmid. Vaccination with recombinant CjaA subcutaneously at the same intervals significantly reduced the caecal load of C. jejuni at three and four weeks post-challenge. Taken together these data imply that responses directed against CjaA, rather than competitive or cross-protective effects mediated by the carrier, confer protection. The impact of varying parameters on the efficacy of the S. Typhimurium DeltaaroA vaccine expressing TetC-CjaA was also tested. Delaying the age at primary vaccination had little impact on protection or humoral responses to CjaA. The use of the parent strain as carrier or changing the attenuating mutation of the carrier to DeltaspaS or DeltassaU enhanced the protective effect

  8. Mucosal immunization with live attenuated Francisella novicida U112ΔiglB protects against pulmonary F. tularensis SCHU S4 in the Fischer 344 rat model.

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    Aimee L Signarovitz

    Full Text Available The need for an efficacious vaccine against Francisella tularensis is a consequence of its low infectious dose and high mortality rate if left untreated. This study sought to characterize a live attenuated subspecies novicida-based vaccine strain (U112ΔiglB in an established second rodent model of pulmonary tularemia, namely the Fischer 344 rat using two distinct routes of vaccination (intratracheal [i.t.] and oral. Attenuation was verified by comparing replication of U112ΔiglB with wild type parental strain U112 in F344 primary alveolar macrophages. U112ΔiglB exhibited an LD(50>10(7 CFU compared to the wild type (LD(50 = 5 × 10(6 CFU i.t.. Immunization with 10(7 CFU U112ΔiglB by i.t. and oral routes induced antigen-specific IFN-γ and potent humoral responses both systemically (IgG2a>IgG1 in serum and at the site of mucosal vaccination (respiratory/intestinal compartment. Importantly, vaccination with U112ΔiglB by either i.t. or oral routes provided equivalent levels of protection (50% survival in F344 rats against a subsequent pulmonary challenge with ~25 LD(50 (1.25 × 10(4 CFU of the highly human virulent strain SCHU S4. Collectively, these results provide further evidence on the utility of a mucosal vaccination platform with a defined subsp. novicida U112ΔiglB vaccine strain in conferring protective immunity against pulmonary tularemia.

  9. A rapid immunization strategy with a live attenuated tetravalent dengue vaccine elicits protective neutralizing antibody responses in non-human primates

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    Yuping eAmbuel

    2014-06-01

    Full Text Available Dengue viruses (DENVs cause approximately 390 million cases of DENV infections annually and over 3 billion people worldwide are at risk of infection. No dengue vaccine is currently available nor is there an antiviral therapy for DENV infections. We have developed a tetravalent live-attenuated DENV vaccine (TDV that consists of a molecularly characterized attenuated DENV-2 strain (TDV-2 and three chimeric viruses containing the pre-membrane and envelope genes of DENV-1, -3 and -4 expressed in the context of the TDV-2 genome. To impact dengue vaccine delivery in endemic areas and immunize travelers, a simple and rapid immunization strategy (RIS is preferred. We investigated RIS consisting of two full vaccine doses being administered subcutaneously or intradermally on the initial vaccination visit (day 0 at two different anatomical locations with a needle-free disposable syringe jet injection (DSJI delivery devices (PharmaJet in non-human primates (NHP. This vaccination strategy resulted in efficient priming and induction of neutralizing antibody responses to all four DENV serotypes comparable to those elicited by the traditional prime and boost (two months later vaccination schedule. In addition, the vaccine induced CD4+ and CD8+ T cells producing IFN-γ, IL-2, and TNF-α, and targeting the DENV-2 NS1, NS3 and NS5 proteins. Moreover, vaccine-specific T cells were cross-reactive with the non-structural NS3 and NS5 proteins of DENV-4. When animals were challenged with DENV-2 they were protected with no detectable viremia, and exhibited sterilizing immunity (no increase of neutralizing titers post- challenge. RIS could decrease vaccination visits and provide quick immune response to all four DENV serotypes. This strategy could increase vaccination compliance and would be especially advantageous for travelers into endemic areas.

  10. Substrate specificity of the neuraminidase of different mumps virus strains.

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    Klamm, H; Pollex, G

    1984-11-01

    The hydrolysis of neuraminlactose, fetuin, ovomucoid, kappa-caseinglycopeptide and mucine from the bovine submaxillary gland with the neuraminidase (NA) of mumps virus strains Jeryl Lynn, Enders and Berlin 9/76 was investigated to determine the pH-dependence of the reaction with the different substrates. The corresponding curves showed splitting into several peaks with reaction maxima ranging from pH 4.7 to pH 6.7. This occurred probably due to the heterogeneity of the virus samples. The NA of each virus strain had the best reaction affinity to neuraminlactose followed by decreasing affinities to ovomucoid, fetuin and kappa-caseinglycopeptide. The mucine from bovine submaxillary gland was not digested at all. The highest hydrolysis of each substrate was found with the Jeryl Lynn strain, which also possessed the lowest substrate specificity. It was followed by that of strain Enders and finally by isolate Berlin 9/76 which, in turn, had the highest substrate specificity. The lower substrate specificity of mumps virus NA seemed to correlate with a lower degree of its cytopathogenicity for hamster ependyma cells.

  11. Nested PCR for Rapid Detection of Mumps Virus in Cerebrospinal Fluid from Patients with Neurological Diseases

    OpenAIRE

    Poggio, Gustavo Palacios; Rodriguez, Claudia; Cisterna, Daniel; Freire, María Cecilia; Cello, Jerónimo

    2000-01-01

    In this study, we have developed a reverse transcription (RT)-nested polymerase chain reaction (n-PCR) for the detection of mumps virus RNA in cerebrospinal fluid (CSF) from patients with neurological infections. A specific 112-bp fragment was amplified by this method with primers from the nucleoprotein of the mumps virus genome. The mumps virus RT–n-PCR was capable of detecting 0.001 PFU/ml and 0.005 50% tissue culture infective dose/ml. This method was found to be specific, since no PCR pro...

  12. Cellular Immune Responses to Live Attenuated Japanese Encephalitis (JE Vaccine SA14-14-2 in Adults in a JE/Dengue Co-Endemic Area.

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    Lance Turtle

    2017-01-01

    Full Text Available Japanese encephalitis (JE virus (JEV causes severe epidemic encephalitis across Asia, for which the live attenuated vaccine SA14-14-2 is being used increasingly. JEV is a flavivirus, and is closely related to dengue virus (DENV, which is co-endemic in many parts of Asia, with clinically relevant interactions. There is no information on the human T cell response to SA14-14-2, or whether responses to SA14-14-2 cross-react with DENV. We used live attenuated JE vaccine SA14-14-2 as a model for studying T cell responses to JEV infection in adults, and to determine whether these T cell responses are cross-reactive with DENV, and other flaviviruses.We conducted a single arm, open label clinical trial (registration: clinicaltrials.gov NCT01656200 to study T cell responses to SA14-14-2 in adults in South India, an area endemic for JE and dengue.Ten out of 16 (62.5% participants seroconverted to JEV SA14-14-2, and geometric mean neutralising antibody (NAb titre was 18.5. Proliferation responses were commonly present before vaccination in the absence of NAb, indicating a likely high degree of previous flavivirus exposure. Thirteen of 15 (87% participants made T cell interferon-gamma (IFNγ responses against JEV proteins. In four subjects tested, at least some T cell epitopes mapped cross-reacted with DENV and other flaviviruses.JEV SA14-14-2 was more immunogenic for T cell IFNγ than for NAb in adults in this JE/DENV co-endemic area. The proliferation positive, NAb negative combination may represent a new marker of long term immunity/exposure to JE. T cell responses can cross-react between JE vaccine and DENV in a co-endemic area, illustrating a need for greater knowledge on such responses to inform the development of next-generation vaccines effective against both diseases.clinicaltrials.gov (NCT01656200.

  13. Cellular Immune Responses to Live Attenuated Japanese Encephalitis (JE) Vaccine SA14-14-2 in Adults in a JE/Dengue Co-Endemic Area.

    Science.gov (United States)

    Turtle, Lance; Tatullo, Filippo; Bali, Tanushka; Ravi, Vasanthapuram; Soni, Mohammed; Chan, Sajesh; Chib, Savita; Venkataswamy, Manjunatha M; Fadnis, Prachi; Yaïch, Mansour; Fernandez, Stefan; Klenerman, Paul; Satchidanandam, Vijaya; Solomon, Tom

    2017-01-01

    Japanese encephalitis (JE) virus (JEV) causes severe epidemic encephalitis across Asia, for which the live attenuated vaccine SA14-14-2 is being used increasingly. JEV is a flavivirus, and is closely related to dengue virus (DENV), which is co-endemic in many parts of Asia, with clinically relevant interactions. There is no information on the human T cell response to SA14-14-2, or whether responses to SA14-14-2 cross-react with DENV. We used live attenuated JE vaccine SA14-14-2 as a model for studying T cell responses to JEV infection in adults, and to determine whether these T cell responses are cross-reactive with DENV, and other flaviviruses. We conducted a single arm, open label clinical trial (registration: clinicaltrials.gov NCT01656200) to study T cell responses to SA14-14-2 in adults in South India, an area endemic for JE and dengue. Ten out of 16 (62.5%) participants seroconverted to JEV SA14-14-2, and geometric mean neutralising antibody (NAb) titre was 18.5. Proliferation responses were commonly present before vaccination in the absence of NAb, indicating a likely high degree of previous flavivirus exposure. Thirteen of 15 (87%) participants made T cell interferon-gamma (IFNγ) responses against JEV proteins. In four subjects tested, at least some T cell epitopes mapped cross-reacted with DENV and other flaviviruses. JEV SA14-14-2 was more immunogenic for T cell IFNγ than for NAb in adults in this JE/DENV co-endemic area. The proliferation positive, NAb negative combination may represent a new marker of long term immunity/exposure to JE. T cell responses can cross-react between JE vaccine and DENV in a co-endemic area, illustrating a need for greater knowledge on such responses to inform the development of next-generation vaccines effective against both diseases. clinicaltrials.gov (NCT01656200).

  14. Cellular Immune Responses to Live Attenuated Japanese Encephalitis (JE) Vaccine SA14-14-2 in Adults in a JE/Dengue Co-Endemic Area

    Science.gov (United States)

    Tatullo, Filippo; Bali, Tanushka; Ravi, Vasanthapuram; Soni, Mohammed; Chan, Sajesh; Chib, Savita; Venkataswamy, Manjunatha M.; Fadnis, Prachi; Yaïch, Mansour; Fernandez, Stefan; Klenerman, Paul; Satchidanandam, Vijaya; Solomon, Tom

    2017-01-01

    Background Japanese encephalitis (JE) virus (JEV) causes severe epidemic encephalitis across Asia, for which the live attenuated vaccine SA14-14-2 is being used increasingly. JEV is a flavivirus, and is closely related to dengue virus (DENV), which is co-endemic in many parts of Asia, with clinically relevant interactions. There is no information on the human T cell response to SA14-14-2, or whether responses to SA14-14-2 cross-react with DENV. We used live attenuated JE vaccine SA14-14-2 as a model for studying T cell responses to JEV infection in adults, and to determine whether these T cell responses are cross-reactive with DENV, and other flaviviruses. Methods We conducted a single arm, open label clinical trial (registration: clinicaltrials.gov NCT01656200) to study T cell responses to SA14-14-2 in adults in South India, an area endemic for JE and dengue. Results Ten out of 16 (62.5%) participants seroconverted to JEV SA14-14-2, and geometric mean neutralising antibody (NAb) titre was 18.5. Proliferation responses were commonly present before vaccination in the absence of NAb, indicating a likely high degree of previous flavivirus exposure. Thirteen of 15 (87%) participants made T cell interferon-gamma (IFNγ) responses against JEV proteins. In four subjects tested, at least some T cell epitopes mapped cross-reacted with DENV and other flaviviruses. Conclusions JEV SA14-14-2 was more immunogenic for T cell IFNγ than for NAb in adults in this JE/DENV co-endemic area. The proliferation positive, NAb negative combination may represent a new marker of long term immunity/exposure to JE. T cell responses can cross-react between JE vaccine and DENV in a co-endemic area, illustrating a need for greater knowledge on such responses to inform the development of next-generation vaccines effective against both diseases. Trial Registration clinicaltrials.gov (NCT01656200) PMID:28135273

  15. Drug: D05089 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D05089 Drug Freeze-dried live attenuated mumps vaccine (JP16); Freeze-dried live attenuated mumps vaccine... (TN) vaccine [DS:H00396] Therapeutic category: 6313 ATC code: J07BE01 map07044 Antivi...asites 63 Biological preparations 631 Vaccines 6313 Viral vaccines D05089 Freeze-...dried live attenuated mumps vaccine (JP16) Anatomical Therapeutic Chemical (ATC) classification [BR:br08303]... J ANTIINFECTIVES FOR SYSTEMIC USE J07 VACCINES J07B VIRAL VACCINES J07BE Mumps vaccines J07BE01 Mumps, live

  16. Comparisons of the humoral and cellular immunity induced by live A16R attenuated spore and AVA-like anthrax vaccine in mice.

    Science.gov (United States)

    Lv, Jin; Zhang, Ying-Ying; Lu, Xun; Zhang, Hao; Wei, Lin; Gao, Jun; Hu, Bin; Hu, Wen-Wei; Hu, Dun-Zhong; Jia, Na; Feng, Xin

    2017-03-01

    The live attenuated anthrax vaccine and anthrax vaccine adsorbed (AVA) are two main types of anthrax vaccines currently used in human. However, the immunoprotective mechanisms are not fully understood. In this study, we compared humoral and cellular immunity induced by live A16R spore vaccine and A16R strain derived AVA-like vaccine in mice peripheral blood, spleen and bone marrow. Both A16R spores and AVA-like vaccines induced a sustained IgG antibody response with IgG1/IgG2b subtype dominance. However, A16R spores vaccine induced higher titer of IgG2a compared with AVA-like vaccine, indicating a stronger Th1 response to A16R spores. Using antigen-specific ELISpot assay, we observed a significant response of ASCs (antibody secreting cells) and IL4-CSCs (cytokine secreting cells) in mice. Specially, there was a positive correlation between the frequencies of antigen specific ASCs and IL4-CSCs in bone marrow derived cells, either by A16R spore or AVA-like vaccine vaccination. Moreover, we also found A16R spore vaccine, not AVA-like vaccine, could induce sustained frequency of IFN-γ-CSCs in bone marrow derived cells. Collectively, both the vaccines induced a mixed Th1/Th2 response with Th2 dominance in mice and A16R spore vaccine might provide a more comprehensive protection because of humoral and cellular immunity induced in bone marrow. Copyright © 2017 International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.

  17. Construction of a Streptococcus iniae sortase A mutant and evaluation of its potential as an attenuated modified live vaccine in Nile tilapia (Oreochromis niloticus).

    Science.gov (United States)

    Wang, J; Zou, L L; Li, A X

    2014-10-01

    Streptococcus iniae is a major Gram-positive aquatic pathogen, which causes invasive diseases in cultured fish worldwide. The identification of potential virulence determinants of streptococcal infections will help to understand and control this disease, but only a few have been confirmed in S. iniae. Sortase A (srtA) is the key enzyme that anchors pre-mature cell wall-attached proteins to peptidoglycan and it can affect the correct positioning of surface proteins, as well as the course of Gram-positive bacterial infection, thereby making it a potential target in the study of virulence factors and disease control. In this study, the 759 bp srtA gene was cloned from pathogenic S. iniae TBY-1 strain and the mutant strain TBY-1ΔsrtA was constructed via allelic exchange mutagenesis. We found that srtA shares high similarities with sortase A from other Streptococcus spp. Direct survival rate assay and challenge experiments were performed, which showed that the mutant strain TBY-1ΔsrtA had a lower survival capacity in healthy tilapia blood and it was less virulent than the wild type strain in tilapia, thereby indicating that the deletion of sortase A affects the virulence and infectious capacity of S. iniae. The mutant strain TBY-1ΔsrtA was used as a live vaccine, which was administered via intraperitoneal injection, and it provided the relative percent survival value of 95.5% in Nile tilapia, thereby demonstrating its high potential as an effective attenuated live vaccine candidate.

  18. A bivalent live-attenuated influenza vaccine for the control and prevention of H3N8 and H3N2 canine influenza viruses.

    Science.gov (United States)

    Rodriguez, Laura; Nogales, Aitor; Murcia, Pablo R; Parrish, Colin R; Martínez-Sobrido, Luis

    2017-08-03

    Canine influenza viruses (CIVs) cause a contagious respiratory disease in dogs. CIV subtypes include H3N8, which originated from the transfer of H3N8 equine influenza virus (EIV) to dogs; and the H3N2, which is an avian-origin virus adapted to infect dogs. Only inactivated influenza vaccines (IIVs) are currently available against the different CIV subtypes. However, the efficacy of these CIV IIVs is not optimal and improved vaccines are necessary for the efficient prevention of disease caused by CIVs in dogs. Since live-attenuated influenza vaccines (LAIVs) induce better immunogenicity and protection efficacy than IIVs, we have combined our previously described H3N8 and H3N2 CIV LAIVs to create a bivalent vaccine against both CIV subtypes. Our findings show that, in a mouse model of infection, the bivalent CIV LAIV is safe and able to induce, upon a single intranasal immunization, better protection than that induced by a bivalent CIV IIV against subsequent challenge with H3N8 or H3N2 CIVs. These protection results also correlated with the ability of the bivalent CIV LAIV to induce better humoral immune responses. This is the first description of a bivalent LAIV for the control and prevention of H3N8 and H3N2 CIV infections in dogs. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Identification of immunogenic proteins associated with protection against haemorrhagic septicaemia after vaccination of calves with a live-attenuated aroA derivative of Pasteurella multocida B:2.

    Science.gov (United States)

    Ataei, Saeed; Burchmore, Richard; Christopher Hodgson, J; Finucane, Anna; Parton, Roger; Coote, John G

    2009-10-01

    Pasteurella multocida serotype B:2 is the causative agent of haemorrhagic septicaemia (HS), a fatal disease of cattle and buffaloes. As a step towards the identification of individual antigens that may protect against HS, proteins present in a sonicated cell extract (SCE) and outer-membrane protein (OMP) preparation of a wild-type P. multocida serotype B:2 were investigated by immunoblotting with sera from calves which had been protected against challenge with a virulent strain of P. multocida B:2 by vaccination with a live-attenuated aroA derivative of the challenge strain. Five proteins in SCE, of approximately 50, 37, 30, 26 and 16 kDa, were recognised by the sera. In an OMP preparation, two bands, at 37 and 50 kDa, were recognised as strongly immunogenic. Mass spectrometry analysis of proteins corresponding in size to those detected by immunoblotting identified the 37 kDa band as OmpA, but the band at 50 kDa was not identified with certainty. A major 30 kDa OMP, identified as OmpH, was not strongly immunogenic.

  20. Comparison of the immunogenicity and safety of measles vaccine administered alone or with live, attenuated Japanese encephalitis SA 14-14-2 vaccine in Philippine infants.

    Science.gov (United States)

    Gatchalian, Salvacion; Yao, Yafu; Zhou, Benli; Zhang, Lei; Yoksan, Sutee; Kelly, Kim; Neuzil, Kathleen M; Yaïch, Mansour; Jacobson, Julie

    2008-04-24

    Japanese encephalitis (JE) virus is a major cause of disease, disability, and death in Asia. An effective, live, attenuated JE vaccine (LJEV) is available; however, its use in routine immunization schedules is hampered by lack of data on concomitant administration with measles vaccine (MV). This study evaluated the immunogenicity and reactogenicity of LJEV and MV when administered at the same or separate study visits in infants younger than 1 year of age. Three groups of healthy infants were randomized to receive LJEV at age of 8 months and MV at 9 months (Group 1; n=100); MV and LJEV together at 9 months (Group 2; n=236); or MV and LJEV at 9 and 10 months, respectively (Group 3; n=235). Blood was obtained 4 weeks after each vaccine administration to determine antibody levels for measles and JE. Reactogenicity was assessed by parental diaries and clinic visits. Four weeks after immunization, measles seroprotection rates (defined as > or =340 mIU/ml) were high and comparable in all three groups and specifically, rates in the combined MV-LJEV (Group 2) were not statistically inferior to those in Group 3 receiving MV separately (96% versus 100%, respectively). Likewise, the LJEV seroprotection rates were high and similar between the three groups. The reactogenicity profiles of the three vaccine schedules were also analogous. LJEV and MV administered together are well tolerated and immunogenic in infants younger than 1 year. These results should facilitate incorporation of LJEV into routine immunization schedules with MV.

  1. A live attenuated strain of Yersinia pestis ΔyscB provides protection against bubonic and pneumonic plagues in mouse model.

    Science.gov (United States)

    Zhang, Xuecan; Qi, Zhizhen; Du, Zongmin; Bi, Yujing; Zhang, Qingwen; Tan, Yafang; Yang, Huiying; Xin, Youquan; Yang, Ruifu; Wang, Xiaoyi

    2013-05-24

    To develop a safe and effective live plague vaccine, the ΔyscB mutant was constructed based on Yersinia pestis biovar Microtus strain 201 that is avirulent to humans, but virulent to mice. The virulence, immunogenicity and protective efficacy of the ΔyscB mutant were evaluated in this study. The results showed that the ΔyscB mutant was severely attenuated, elicited a higher F1-specific antibody titer and provided protective efficacy against bubonic and pneumonic plague in mouse model. The ΔyscB mutant could induce the secretion of both Th1-associated cytokines (IFN-γ, IL-2 and TNF-α) and Th2-associated cytokines (IL-4 and IL-10). Taken together, the ΔyscB mutant represented a potential vaccine candidate based on its ability to generate strong humoral and cell-mediated immune responses and to provide good protection against both subcutaneous and intranasal Y. pestis challenge. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. OMOLOGICAL AND HETEROLOGICAL ANTIBODY AND T CELL IMMUNE RESPONSES TO LIVE ATTENUATED INFLUENZA VACCINE A (H5N2 AND A (H7N3

    Directory of Open Access Journals (Sweden)

    A. N. Naykhin

    2015-01-01

    Full Text Available From the beginning of 21th century outbreaks of H5, H7 and H9 avian flu are registered from time to time. These viruses are considered as one of the possible causes of the next pandemia. The development of avian influenza vaccines is one of the WHO priorities. The aim of this work was to study antibody and cellular immune responses to avian A (H5N2 and A (H7N3 live attenuated influenza vaccines (LAIVs. We examined serum antibodies (HAI assay, microneutralization assay, ELISA, local antibodies (ELISA and virus-specific CD4+ and CD8+ central memory and effector memory T cells. Two doses vaccination of healthy volunteers with A (H5N2 and A (H7N3 LAIVs induced homological antibody and cellular immune responses (i. e. serum and local antibody conversions, virus-specific memory T cell growth. These vaccines also stimulated heterological immunity (heterological serum and local antibodies and T cells. Heterological immune response intensity depended on antigenic structure of vaccine strain and heterological virus, particularly on HA type. 

  3. Oral infection with the Salmonella enterica serovar Gallinarum 9R attenuated live vaccine as a model to characterise immunity to fowl typhoid in the chicken

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    Beal Richard

    2005-09-01

    Full Text Available Abstract Background Salmonella enterica serovar Gallinarum (S. Gallinarum is the causative agent of fowl typhoid, a severe systemic disease of chickens that results in high mortality amongst infected flocks. Due to its virulence, the immune response to S. Gallinarum is poorly characterised. In this study we have utilised infection by the live attenuated S. Gallinarum 9R vaccine strain in inbred chickens to characterise humoral, cellular and cytokine responses to systemic salmonellosis. Results Infection with 9R results in a mild systemic infection. Bacterial clearance at three weeks post infection coincides with increases in circulating anti-Salmonella antibodies, increased T cell proliferation to Salmonella challenge and increased expression of interferon gamma. These responses peak at four weeks post infection, then decline. Only modest increases of expression of the pro-inflammatory cytokine interleukin-1β were detected early in the infection. Conclusion Infection of chickens with the 9R vaccine strain induces a mild form of systemic salmonellosis. This induces both cellular and humoral immune responses, which peak soon after bacterial clearance. Unlike enteric-associated Salmonella infections the immune response is not prolonged, reflecting the absence of persistence of Salmonella in the gastrointestinal tract. The findings here indicate that the use of the S. Gallinarum 9R vaccine strain is an effective model to study immunity to systemic salmonellosis in the chicken and may be employed in further studies to determine which components of the immune response are needed for protection.

  4. Innate and adaptive cellular immunity in flavivirus-naïve human recipients of a live-attenuated dengue serotype 3 vaccine produced in Vero cells (VDV3).

    Science.gov (United States)

    Sanchez, Violette; Gimenez, Sophie; Tomlinson, Brian; Chan, Paul K S; Thomas, G Neil; Forrat, Remi; Chambonneau, Laurent; Deauvieau, Florence; Lang, Jean; Guy, Bruno

    2006-06-05

    VDV3, a clonal derivative of the Mahidol live-attenuated dengue 3 vaccine was prepared in Vero cells. Despite satisfactory preclinical evaluation, VDV3 was reactogenic in humans. We explored whether immunological mechanisms contributed to this outcome by monitoring innate and adaptive cellular immune responses for 28 days after vaccination. While no variations were seen in serum IL12 or TNFalpha levels, a high IFNgamma secretion was detected from Day 8, concomitant to IFNalpha, followed by IL10. Specific Th1 and CD8 responses were detected on Day 28, with high IFNgamma/TNFalpha ratios. Vaccinees exhibited very homogeneous class I HLA profiles, and a new HLA B60-restricted CD8 epitope was identified in NS3. We propose that, among other factors, adaptive immunity may have contributed to reactogenicity, even after this primary vaccination. In addition, the unexpected discordance observed between preclinical results and clinical outcome in humans led us to reconsider some of our preclinical acceptance criteria. Lessons learned from these results will help us to pursue the development of safe and immunogenic vaccines.

  5. The clinical efficacy study of live attenuated influenza vaccines%流感减毒活疫苗临床效率的研究进展

    Institute of Scientific and Technical Information of China (English)

    周芳烨

    2012-01-01

    Influenza virus could induce serious respiratory diseases, and the virus has the characters of the antigen shift and genetic reassortment. It leaded to the repeated outbreaks of influenza and even pandemics. The vaccines were the most effective methods to prevent. At present, there were a lot of vaccines about influenza viruses, these vaccines have different immunity efficacy in the population. The clinical efficacy study of live attenuated influenza vaccines is reviewed in this paper.%流感病毒可以引起人类严重的呼吸系统疾病,甚至导致死亡.由于病毒具有高突变率及其抗原漂移、基因重配等特性,因此导致流感的反复暴发,甚至大流行.疫苗是预防流感最有效的手段,不同种类的流感疫苗在不同人群中会产生不同的免疫效果,本文就流感减毒活疫苗的临床效率作一综述.

  6. Safety and protective efficacy of a spiC and crp deletion mutant of Salmonella gallinarum as a live attenuated vaccine for fowl typhoid.

    Science.gov (United States)

    Cheng, Zhao; Yin, Junlei; Kang, Xilong; Geng, Shizhong; Hu, Maozhi; Pan, Zhiming; Jiao, Xinan

    2016-08-01

    With an aim to develop a safe, immunogenic fowl typhoid (FT) vaccine, the safety and efficacy of 1009ΔspiCΔcrp, a spiC and crp deletion mutant of Salmonella gallinarum, were evaluated in chickens. Three-day-old chickens were intramuscularly immunized with 1009ΔspiCΔcrp (1×10(7)CFU) and boosted 7days later (at 10-days old) with the same dose and via the same route (vaccinated group). The vaccinated group showed no clinical symptoms and no differences in body weight compared to the unvaccinated control group. 1009ΔspiCΔcrp bacteria colonized and persisted in the liver and spleen of vaccinated chickens for >14days, and significant specific humoral and cellular immune responses were induced. Vaccinated chickens were challenged with S. gallinarum strain SG9 at 21days post-immunization (24-day-old chickens), and efficient protection was observed based on the mortality and clinical symptoms, as compared to those in the control group. These results demonstrate that 1009ΔspiCΔcrp can be used as a live attenuated vaccine.

  7. Development of TV003/TV005, a single dose, highly immunogenic live attenuated dengue vaccine; what makes this vaccine different from the Sanofi-Pasteur CYD™ vaccine?

    Science.gov (United States)

    Whitehead, Stephen S

    2016-01-01

    Dengue is caused by four serotype-distinct dengue viruses (DENVs), and developing a multivalent vaccine against dengue has not been straightforward since partial immunity to DENV may predispose to more severe disease upon subsequent DENV infection. The vaccine that is furthest along in development is CYD™, a live attenuated tetravalent vaccine (LATV) produced by Sanofi Pasteur. Although the multi-dose vaccine demonstrated protection against severe dengue, its overall efficacy was limited by DENV serotype, serostatus at vaccination, region and age. The National Institute of Allergy and Infectious Diseases has developed the LATV dengue vaccines TV003/TV005. A single dose of either TV003 or TV005 induced seroconversion to four DENV serotypes in 74-92% (TV003) and 90% (TV005) of flavivirus seronegative adults and elicited near-sterilizing immunity to a second dose of vaccine administered 6-12 months later. The important differences in the structure, infectivity and immune responses to TV003/TV005 are compared with CYD™.

  8. FDA Researchers Advance Science for Vaccines to Prevent Mumps and Whooping Cough

    Science.gov (United States)

    ... Advance Science for Vaccines to Prevent Mumps and Whooping Cough Share Tweet Linkedin Pin it More sharing options ... in the FDA’s laboratories in Silver Spring, MD. Whooping Cough: Background and Key Findings The FDA is studying ...

  9. MMRV (Measles, Mumps, Rubella, and Varicella) Vaccine: What You Need to Know

    Science.gov (United States)

    ... STATEMENT MMRV Vaccine What You Need to Know (Measles, Mumps, Rubella and Varicella) Many Vaccine Information Statements ... and V aricella (chickenpox) can be serious diseases: Measles • Causes rash, cough, runny nose, eye irritation, fever. • ...

  10. The potential dysfunction of otolith organs in patients after mumps infection

    OpenAIRE

    Zhou, Yu-juan; Yu, Jing; Wu, Yong-Zhen; Tian, Liang; Han, Zhao; Wang, Jing; Chi, Fang-lu

    2017-01-01

    Objective To investigate the relationship between mumps and the extent of hearing impairment and otolith organ damage. Methods A total of 27 patients with unilateral hearing impairment following mumps were enrolled. The degrees of hearing loss and otolith organ damage were confirmed by audiometric and vestibular evoked myogenic potential [VEMP] tests. All the results were compared and analyzed using Stata 13.0 software for Windows. Results The VEMP thresholds of the affected ears were signifi...

  11. Boosted influenza-specific T cell responses after H5N1 pandemic live attenuated influenza virus (pLAIV vaccination

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    Yanchun ePeng

    2015-06-01

    Full Text Available Background: In a phase I clinical trial, a H5N1 pandemic live attenuated influenza virus (pLAIV VN2004 vaccine bearing avian influenza H5N1 HA and NA genes on the A/Ann Arbor cold-adapted vaccine backbone displayed very restricted replication. We evaluated T cell responses to H5N1 pLAIV vaccination and assessed pre-existing T cell responses to to determine whether they were associated with restricted replication of the H5N1 pLAIV. Method: ELISPOT assays were performed using pools of overlapping peptides spanning the entire H5N1 proteome and the hemagglutinin (HA proteins of relevant seasonal H1N1 and H3N2 viruses. We tested stored PBMCs from 21 study subjects who received two doses of the H5N1 pLAIV. The PBMCs were collected 1 day before and 7 days after the first and second pLAIV vaccine doses, respectively. Result: T cell responses to conserved internal proteins M and NP were significantly boosted by vaccination (p=0.036. In addition, H5N1 pLAIV appeared to preferentially stimulate and boost pre-existing seasonal influenza virus HA-specific T cell responses that showed low cross-reactivity with the H5 HA. We confirmed this observation by T cell cloning and identified a novel HA-specific epitope. However, we did not find any evidence that pre-existing T cells prevented pLAIV replication and take. Conclusion: We found that cross-reactive T cell responses could be boosted by pLAIV regardless of the induction of antibody. The impact of the original antigenic sin phenomenon in a subset of volunteers, with preferential expansion of seasonal influenza-specific but not H5N1-specific T cell responses merits further investigation.

  12. A new generation of modified live-attenuated avian influenza viruses using a two-strategy combination as potential vaccine candidates.

    Science.gov (United States)

    Song, Haichen; Nieto, Gloria Ramirez; Perez, Daniel R

    2007-09-01

    In light of the recurrent outbreaks of low pathogenic avian influenza (LPAI) and highly pathogenic avian influenza (HPAI), there is a pressing need for the development of vaccines that allow rapid mass vaccination. In this study, we introduced by reverse genetics temperature-sensitive mutations in the PB1 and PB2 genes of an avian influenza virus, A/Guinea Fowl/Hong Kong/WF10/99 (H9N2) (WF10). Further genetic modifications were introduced into the PB1 gene to enhance the attenuated (att) phenotype of the virus in vivo. Using the att WF10 as a backbone, we substituted neuraminidase (NA) for hemagglutinin (HA) for vaccine purposes. In chickens, a vaccination scheme consisting of a single dose of an att H7N2 vaccine virus at 2 weeks of age and subsequent challenge with the wild-type H7N2 LPAI virus resulted in complete protection. We further extended our vaccination strategy against the HPAI H5N1. In this case, we reconstituted an att H5N1 vaccine virus, whose HA and NA genes were derived from an Asian H5N1 virus. A single-dose immunization in ovo with the att H5N1 vaccine virus in 18-day-old chicken embryos resulted in more than 60% protection for 4-week-old chickens and 100% protection for 9- to 12-week-old chickens. Boosting at 2 weeks posthatching provided 100% protection against challenge with the HPAI H5N1 virus for chickens as young as 4 weeks old, with undetectable virus shedding postchallenge. Our results highlight the potential of live att avian influenza vaccines for mass vaccination in poultry.

  13. Effect of Broccoli Sprouts and Live Attenuated Influenza Virus on Peripheral Blood Natural Killer Cells: A Randomized, Double-Blind Study.

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    Loretta Müller

    Full Text Available Enhancing antiviral host defense responses through nutritional supplementation would be an attractive strategy in the fight against influenza. Using inoculation with live attenuated influenza virus (LAIV as an infection model, we have recently shown that ingestion of sulforaphane-containing broccoli sprout homogenates (BSH reduces markers of viral load in the nose. To investigate the systemic effects of short-term BSH supplementation in the context of LAIV-inoculation, we examined peripheral blood immune cell populations in non-smoking subjects from this study, with a particular focus on NK cells. We carried out a randomized, double-blinded, placebo-controlled study measuring the effects of BSH (N = 13 or placebo (alfalfa sprout homogenate, ASH; N = 16 on peripheral blood mononuclear cell responses to a standard nasal vaccine dose of LAIV in healthy volunteers. Blood was drawn prior to (day-1 and post (day2, day21 LAIV inoculation and analyzed for neutrophils, monocytes, macrophages, T cells, NKT cells, and NK cells. In addition, NK cells were enriched, stimulated, and assessed for surface markers, intracellular markers, and cytotoxic potential by flow cytometry. Overall, LAIV significantly reduced NKT (day2 and day21 and T cell (day2 populations. LAIV decreased NK cell CD56 and CD158b expression, while significantly increasing CD16 expression and cytotoxic potential (on day2. BSH supplementation further increased LAIV-induced granzyme B production (day2 in NK cells compared to ASH and in the BSH group granzyme B levels appeared to be negatively associated with influenza RNA levels in nasal lavage fluid cells. We conclude that nasal influenza infection may induce complex changes in peripheral blood NK cell activation, and that BSH increases virus-induced peripheral blood NK cell granzyme B production, an effect that may be important for enhanced antiviral defense responses.ClinicalTrials.gov NCT01269723.

  14. Live Attenuated Influenza Vaccine Strains Elicit a Greater Innate Immune Response than Antigenically-Matched Seasonal Influenza Viruses during Infection of Human Nasal Epithelial Cell Cultures

    Science.gov (United States)

    Fischer, William A.; Brighton, Missy; Jaspers, Ilona

    2014-01-01

    Influenza viruses are global pathogens that infect approximately 10–20% of the world’s population each year. Vaccines, including the live attenuated influenza vaccine (LAIV), are the best defense against influenza infections. The LAIV is a novel vaccine that actively replicates in the human nasal epithelium and elicits both mucosal and systemic protective immune responses. The differences in replication and innate immune responses following infection of human nasal epithelium with influenza seasonal wild type (WT) and LAIV viruses remain unknown. Using a model of primary differentiated human nasal epithelial cell (hNECs) cultures, we compared influenza WT and antigenically-matched cold adapted (CA) LAIV virus replication and the subsequent innate immune response including host cellular pattern recognition protein expression, host innate immune gene expression, secreted pro-inflammatory cytokine production, and intracellular viral RNA levels. Growth curves comparing virus replication between WT and LAIV strains revealed significantly less infectious virus production during LAIV compared with WT infection. Despite this disparity in infectious virus production the LAIV strains elicited a more robust innate immune response with increased expression of RIG-I, TLR-3, IFNβ, STAT-1, IRF-7, MxA, and IP-10. There were no differences in cytotoxicity between hNEC cultures infected with WT and LAIV strains as measured by basolateral levels of LDH. Elevated levels of intracellular viral RNA during LAIV as compared with WT virus infection of hNEC cultures at 33°C may explain the augmented innate immune response via the up-regulation of pattern recognition receptors and down-stream type I IFN expression. Taken together our results suggest that the decreased replication of LAIV strains in human nasal epithelial cells is associated with a robust innate immune response that differs from infection with seasonal influenza viruses, limits LAIV shedding and plays a role in the

  15. Live attenuated influenza vaccine strains elicit a greater innate immune response than antigenically-matched seasonal influenza viruses during infection of human nasal epithelial cell cultures.

    Science.gov (United States)

    Fischer, William A; Chason, Kelly D; Brighton, Missy; Jaspers, Ilona

    2014-03-26

    Influenza viruses are global pathogens that infect approximately 10-20% of the world's population each year. Vaccines, including the live attenuated influenza vaccine (LAIV), are the best defense against influenza infections. The LAIV is a novel vaccine that actively replicates in the human nasal epithelium and elicits both mucosal and systemic protective immune responses. The differences in replication and innate immune responses following infection of human nasal epithelium with influenza seasonal wild type (WT) and LAIV viruses remain unknown. Using a model of primary differentiated human nasal epithelial cell (hNECs) cultures, we compared influenza WT and antigenically-matched cold adapted (CA) LAIV virus replication and the subsequent innate immune response including host cellular pattern recognition protein expression, host innate immune gene expression, secreted pro-inflammatory cytokine production, and intracellular viral RNA levels. Growth curves comparing virus replication between WT and LAIV strains revealed significantly less infectious virus production during LAIV compared with WT infection. Despite this disparity in infectious virus production the LAIV strains elicited a more robust innate immune response with increased expression of RIG-I, TLR-3, IFNβ, STAT-1, IRF-7, MxA, and IP-10. There were no differences in cytotoxicity between hNEC cultures infected with WT and LAIV strains as measured by basolateral levels of LDH. Elevated levels of intracellular viral RNA during LAIV as compared with WT virus infection of hNEC cultures at 33°C may explain the augmented innate immune response via the up-regulation of pattern recognition receptors and down-stream type I IFN expression. Taken together our results suggest that the decreased replication of LAIV strains in human nasal epithelial cells is associated with a robust innate immune response that differs from infection with seasonal influenza viruses, limits LAIV shedding and plays a role in the silent

  16. Gut-homing conventional plasmablasts and CD27- plasmablasts elicited after a short time exposure to an oral live attenuated Shigella vaccine candidate in humans

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    Franklin R. Toapanta

    2014-08-01

    Full Text Available Currently, there is no licensed Shigella vaccine; however, various promising live attenuated vaccine candidates have emerged, including CVD1208S (ΔguaBA, Δset, Δsen S. flexneri 2a, which was shown to be safe and immunogenic in Phase 1 clinical trials. Here we report the immune responses elicited in an outpatient Phase 2 clinical trial in which subjects were vaccinated with CVD 1208S. Oral immunization with CVD 1208S elicited high anti-S. flexneri 2a LPS and IpaB antibody responses, as well as an acute plasmablast (PB infiltration in peripheral blood 7 days after immunization. PB sorted based on their expression of homing molecules confirmed that cells expressing integrin α4β7 alone or in combination with CD62L were responsible for antibody production (as measured by ELISpot. Furthermore, using high-color flow-cytometry, on day 7 after immunization, we observed the appearance of conventional PB (CPB, CD19dim CD20- CD27+high CD38+high CD3-, as well as a PB population that did not express CD27 (CD27- PB; pre-plasmablasts. The pattern of individual or simultaneous expression of homing markers (integrin α4β7, CD62L, CXCR3 and CXCR4 suggested that CPB cells homed preferentially to the inflamed gut mucosa. In contrast, ~50% CD27- PB cells appear to home to yet to be identified peripheral lymphoid organs or were in a transition state preceding integrin α4β7 upregulation. In sum, these observations demonstrate that strong immune responses, including distinct PB subsets with the potential to home to the gut and other secondary lymphoid organs, can be elicited after a short time of exposure to a shigella oral

  17. Randomized, controlled human challenge study of the safety, immunogenicity, and protective efficacy of a single dose of Peru-15, a live attenuated oral cholera vaccine.

    Science.gov (United States)

    Cohen, Mitchell B; Giannella, Ralph A; Bean, Judy; Taylor, David N; Parker, Susan; Hoeper, Amy; Wowk, Stephen; Hawkins, Jennifer; Kochi, Sims K; Schiff, Gilbert; Killeen, Kevin P

    2002-04-01

    Peru-15 is a live attenuated oral vaccine derived from a Vibrio cholerae O1 El Tor Inaba strain by a series of deletions and modifications, including deletion of the entire CT genetic element. Peru-15 is also a stable, motility-defective strain and is unable to recombine with homologous DNA. We wished to determine whether a single oral dose of Peru-15 was safe and immunogenic and whether it would provide significant protection against moderate and severe diarrhea in a randomized, double-blind, placebo-controlled human volunteer cholera challenge model. A total of 59 volunteers were randomly allocated to groups to receive either 2 x 10(8) CFU of reconstituted, lyophilized Peru-15 vaccine diluted in CeraVacx buffer or placebo (CeraVacx buffer alone). Approximately 3 months after vaccination, 36 of these volunteers were challenged with approximately 10(5) CFU of virulent V. cholerae O1 El Tor Inaba strain N16961, prepared from a standardized frozen inoculum. Among vaccinees, 98% showed at least a fourfold increase in vibriocidal antibody titers. After challenge, 5 (42%) of the 12 placebo recipients and none (0%) of the 24 vaccinees had moderate or severe diarrhea (> or = 3,000 g of diarrheal stool) (P = 0.002; protective efficacy, 100%; lower one-sided 95% confidence limit, 75%). A total of 7 (58%) of the 12 placebo recipients and 1 (4%) of the 24 vaccinees had any diarrhea (P Peru-15 is a well-tolerated and immunogenic oral cholera vaccine that affords protective efficacy against life-threatening cholera diarrhea in a human volunteer challenge model. This vaccine may therefore be a safe and effective tool to prevent cholera in travelers and is a strong candidate for further evaluation to prevent cholera in an area where cholera is endemic.

  18. Dissecting Antibodies Induced by a Chimeric Yellow Fever-Dengue, Live-Attenuated, Tetravalent Dengue Vaccine (CYD-TDV) in Naive and Dengue-Exposed Individuals.

    Science.gov (United States)

    Henein, Sandra; Swanstrom, Jesica; Byers, Anthony M; Moser, Janice M; Shaik, S Farzana; Bonaparte, Matthew; Jackson, Nicholas; Guy, Bruno; Baric, Ralph; de Silva, Aravinda M

    2017-02-01

    Sanofi Pasteur has developed a chimeric yellow fever-dengue, live-attenuated, tetravalent dengue vaccine (CYD-TDV) that is currently approved for use in several countries. In clinical trials, CYD-TDV was efficacious at reducing laboratory-confirmed cases of dengue disease. Efficacy varied by dengue virus (DENV) serotype and prevaccination dengue immune status. We compared the properties of antibodies in naive and DENV-exposed individuals who received CYD-TDV. We depleted specific populations of DENV-reactive antibodies from immune serum samples to estimate the contribution of serotype-cross-reactive and type-specific antibodies to neutralization. Subjects with no preexisting immunity to DENV developed neutralizing antibodies to all 4 serotypes of DENV. Further analysis demonstrated that DENV4 was mainly neutralized by type-specific antibodies whereas DENV1, DENV2, and DENV3 were mainly neutralized by serotype cross-reactive antibodies. When subjects with preexisting immunity to DENV were vaccinated, they developed higher levels of neutralizing antibodies than naive subjects who were vaccinated. In preimmune subjects, CYD-TDV boosted cross-reactive neutralizing antibodies while maintaining type-specific neutralizing antibodies acquired before vaccination. Our results demonstrate that the quality of neutralizing antibodies induced by CYD-TDV varies depending on DENV serotype and previous immune status. We discuss the implications of these results for understanding vaccine efficacy. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  19. Live-attenuated, tetravalent dengue vaccine in children, adolescents and adults in a dengue endemic country: randomized controlled phase I trial in the Philippines.

    Science.gov (United States)

    Capeding, Rosario Z; Luna, Imelda A; Bomasang, Emily; Lupisan, Socorro; Lang, Jean; Forrat, Remi; Wartel, Anh; Crevat, Denis

    2011-05-17

    A recombinant live attenuated tetravalent dengue vaccine (TDV) is safe and immunogenic in adults and children in dengue-naïve populations. Data are needed in dengue endemic populations. In a phase I, randomized, controlled, blind-observer study in the Philippines, groups of participants aged 2-5, 6-11, 12-17, and 18-45 years received either three TDV vaccinations at months 0, 3.5, and 12 (TDV-TDV-TDV group) or licensed typhoid vaccination at month 0 and TDV at months 3.5 and 12 (TyVi-TDV-TDV group) and were followed for safety (including biological safety and vaccine virus viremia) and immunogenicity. No serious adverse vaccine related events and no significant trends in biological safety parameters were reported. Injection site pain, headache, malaise, myalgia, fever, and asthenia were reported most frequently, as mild to moderate in most cases and transient. Reactogenicity did not increase with successive vaccinations and was no higher in children than in adults and adolescents. Low levels of vaccinal viremia were detected in both groups after each TDV vaccination. After three TDV vaccinations, the seropositivity rates against serotypes 1-4 were: 91%, 100%, 96%, 100%, respectively, in 2-5 year-olds; 88%, 96% 96%, 92% in 6-11 year-olds; 88%, 83%, 92%, 96% in adolescents; and 100% for all serotypes in adults. A similar response was observed after two doses for the TyVi-TDV-TDV group. The safety profile of TDV in a flavivirus endemic population was consistent with previous reports from flavivirus naïve populations. A vaccine regimen of either three TDV vaccinations administered over a year or two TDV vaccinations given more than 8 months apart resulted in a balanced antibody response to all four dengue serotypes in this flavivirus-exposed population, including children.

  20. Neutralizing Antibody Responses to Antigenically Drifted Influenza A(H3N2) Viruses among Children and Adolescents following 2014-2015 Inactivated and Live Attenuated Influenza Vaccination

    Science.gov (United States)

    Martin, Judith M.; Gross, F. Liaini; Jefferson, Stacie; Cole, Kelly Stefano; Archibald, Crystal Ann; Nowalk, Mary Patricia; Susick, Michael; Moehling, Krissy; Spencer, Sarah; Chung, Jessie R.; Flannery, Brendan; Zimmerman, Richard K.

    2016-01-01

    Human influenza A(H3N2) viruses that predominated during the moderately severe 2014-2015 influenza season differed antigenically from the vaccine component, resulting in reduced vaccine effectiveness (VE). To examine antibody responses to 2014-2015 inactivated influenza vaccine (IIV) and live-attenuated influenza vaccine (LAIV) among children and adolescents, we collected sera before and after vaccination from 150 children aged 3 to 17 years enrolled at health care facilities. Hemagglutination inhibition (HI) assays were used to assess the antibody responses to vaccine strains. We evaluated cross-reactive antibody responses against two representative A(H3N2) viruses that had antigenically drifted from the A(H3N2) vaccine component using microneutralization (MN) assays. Postvaccination antibody titers to drifted A(H3N2) viruses were higher following receipt of IIV (MN geometric mean titers [GMTs], 63 to 68; 38 to 45% achieved seroconversion) versus LAIV (MN GMT, 22; only 3 to 5% achieved seroconversion). In 9- to 17-year-olds, the highest MN titers were observed among IIV-vaccinated individuals who had received LAIV in the previous season. Among all IIV recipients aged 3 to 17 years, the strongest predictor of antibody responses to the drifted viruses was the prevaccination titers to the vaccine strain. The results of our study suggest that in an antigenically drifted influenza season, vaccination still induced cross-reactive antibody responses to drifted circulating A(H3N2) viruses, although higher antibody titers may be required for protection. Antibody responses to drifted A(H3N2) viruses following vaccination were influenced by multiple factors, including vaccine type and preexisting immunity from prior exposure. PMID:27558294

  1. An integrated multi-study analysis of serum HAI antibody responses to Ann Arbor strain live attenuated influenza vaccine in children and adults

    Directory of Open Access Journals (Sweden)

    Kathleen L. Coelingh

    2014-01-01

    Full Text Available Serum hemagglutination-inhibition (HAI antibodies have been associated with protection from influenza infection. HAI antibody responses to live attenuated influenza vaccines (LAIVs and their role in protection are not fully elucidated. This study characterizes HAI titers for LAIV. Serum HAI data were pooled from 40 LAIV clinical trials enrolling subjects aged 2–49 years. Using pre- and postvaccination titers, geometric mean fold rises (GMFRs and seroresponse rates (⩾4-fold rise were determined by age and baseline serostatus (seronegative ⩽8, seropositive >8. Responses were generally evaluated after 2 doses for those 2–8 years of age and after 1 dose for those 9–49 years of age. Data were available for 6909 children and 3444 adults. A total of 20 different LAIV formulations were used, representing 6 H1N1 strains, 9 H3N2 strains, 7 B/Yamagata lineage strains and 2 B/Victoria lineage strains. GMFRs were modest overall; GMFRs were higher in children versus adults and higher in baseline seronegatives versus baseline seropositives. This difference was greatest among children, with GMFRs ranging from 2.2 to 5.9 among seronegative and 1.2–1.5 among seropositive children. HAI responses were modest overall, higher in seronegative individuals (10.8–61.6% relative to seropositive (1.9–17.0%, and higher in children relative to adults. Postvaccination HAI titers were below those associated with protection for inactivated influenza vaccines. The results suggest that LAIV-induced protection is mediated primarily by mucosal antibody and T-cell immunity, although serum HAI has value as strain-specific marker of response to vaccination, particularly among seronegative individuals.

  2. WHO informal consultation on quality, safety and efficacy specifications for live attenuated rotavirus vaccines Mexico City, Mexico, 8-9 February 2005.

    Science.gov (United States)

    Wood, David

    2005-12-01

    Rotavirus vaccines are at an advanced stage of development but there are as yet no WHO recommendations on production and quality control to provide regulatory guidance. A meeting of experts was convened by WHO and PAHO/AMRO to review the scientific basis for production and quality control of rotavirus vaccines, and to discuss specific measures to assure the safety and efficacy of rotavirus vaccines. The meeting was attended by 25 experts from 14 countries, drawn from academia, public health, national regulatory authorities and vaccine producers. It was agreed that existing guidance for other live virus vaccines provides a very good basis for product characterization, especially for source materials and control of production. The basis for attenuation of current vaccines or vaccine candidates is not known but, at least for the vaccines based on the Jennerian approach of using animal (bovine) rotaviruses, is likely to be multigenic. The risk of intussusception in humans is influenced by genetic background and age. Recent analyzes of large vaccine safety trials found that certain strains of vaccine virus were not associated with intussusception, although in these trials the first dose of vaccine was not administered to children over 3 months of age. Since age is a risk factor for intussusception, this may suggest that early delivery of the first dose of vaccine is desirable. However, maternal antibodies may mitigate against early delivery of the first vaccine dose. Factors which could affect vaccine efficacy or safety include strain diversity, malnutrition, other enteric infections, parasitic infection or immune suppression. It was concluded that data from clinical trials conducted in one part of the world would not necessarily be predictive of vaccine efficacy in other places. It was agreed that in nonclinical evaluations there was a need to use oral dosing for toxicity studies and, because rotavirus is non-neurovirulent, that there was no need for an animal

  3. Comparison of intramuscular and subcutaneous administration of a herpes zoster live-attenuated vaccine in adults aged ≥50 years: a randomised non-inferiority clinical trial.

    Science.gov (United States)

    Diez-Domingo, Javier; Weinke, Thomas; Garcia de Lomas, Juan; Meyer, Claudius U; Bertrand, Isabelle; Eymin, Cécile; Thomas, Stéphane; Sadorge, Christine

    2015-02-04

    Zostavax(®) is a live, attenuated varicella zoster virus (VZV) vaccine developed specifically for the prevention of HZ and PHN in individuals aged ≥50 years. During the clinical development of Zostavax, which was mainly in the US, the vaccine was administrated by the subcutaneous (SC) route. In Europe, many healthcare professionals prefer administering vaccines by the intramuscular (IM) route. This was an open-label, randomised trial conducted in 354 subjects aged ≥50 years. The primary objectives were to demonstrate that IM administration is both non-inferior to SC administration in terms of 4-week post-vaccination geometric mean titres (GMTs), and elicits an acceptable geometric mean fold-rise (GMFR) of antibody titres measured by glycoprotein enzyme-linked immunosorbent assay. Pre-specified non-inferiority was set as the lower bound of the 95% confidence interval (CI) of the GMT ratio (IM/SC) being >0.67. An acceptable GMFR for the IM route was pre-specified as the lower bound of its 95% CI being >1.4. Description of the VZV immune response using the interferon-gamma enzyme-linked immunospot (IFN-γ ELISPOT) assay and of the safety were secondary objectives. Participants were randomised to IM or SC administration (1:1). The baseline demographics were comparable between groups; mean age: 62.6 years (range: 50.0-90.5). The primary immunogenicity objectives were met (per protocol analysis): GMT ratio (IM/SC): 1.05 (95% CI: 0.93-1.18); GMFR: 2.7 (2.4-3.0). VZV immune response using IFN-γ ELISPOT were comparable between groups. Frequencies of systemic adverse events were comparable between groups. Injection-site reactions were less frequent with IM than SC route: erythema (15.9% versus 52.5%), pain (25.6% versus 39.5%) and swelling (13.6% versus 37.3%), respectively. In adults aged ≥50 years, IM administration of Zostavax elicited similar immune responses to SC administration and was well tolerated, with fewer injection-site reactions than with SC

  4. [Effects of the MMR vaccination on the epidemiology of mumps in Germany].

    Science.gov (United States)

    Koch, J; Takla, A

    2013-09-01

    Mumps is an acute viral infectious disease characterized by fever and swelling and tenderness of one or more salivary glands, usually the parotid gland. Since 1976, the German Standing Committee on Vaccination (STIKO) has recommended a mumps vaccination as part of the routine immunization schedule in former West Germany. In East Germany, the vaccination was only introduced in 1991 after reunification. In the preceding decades, no comprehensive surveillance system existed in Germany. However, for East Germany and the successional federal states of former East Germany, data on mumps incidence are available from different Eastern surveillance systems for the time period 1968-2012. According to these data, the incidence of mumps has dropped from > 200 cases/100,000 annually in the pre-vaccine era to currently epidemiology and the increase of outbreaks among adolescents and young adults, the implementation of a nationwide mandatory notification was initiated and came into effect in March 2013. Mandatory notification enables the early detection of outbreaks and obtainment of comprehensive data for evaluation of the immunization program in place. Regarding the long-term prevention of mumps in Germany, it is hoped that--as part of the measles and rubella elimination effort--coverage rates for the second MMR dose among children will increase nationwide above 95% and existing vaccination gaps among adults will be closed.

  5. Acute Pancreatitis from Mumps Re-infection in Adulthood. A Case Report

    Directory of Open Access Journals (Sweden)

    Atsuko Taii

    2008-05-01

    Full Text Available Context Acute pancreatitis is a complication of mumps which mainly affects children who then usually acquire permanent immunity. We present the case of a woman with acute pancreatitis caused by mumps re-infection in adulthood. Case report A 34-year-old woman developed mild acute pancreatitis caused by re-infection with mumps, as confirmed serologically by enzyme-linked immunosorbent assays mumps -specific IgM and IgG. Acute pancreatitis was indicated by the elevation of amylase and other pancreatic enzymes such as lipase and elastase-1 as well as by swelling of the pancreatic head visualized by abdominal computed tomography. The abdominal symptoms were resolved soon after the administration of a pancreatic enzyme inhibitor. As the swelling of the right and left parotids decreased, serum amylase levels also gradually normalized. Conclusion We believe that this is the first reported case of acute pancreatitis caused by mumps re-infection in an adult. Such reinfection should be considered a possible though rare

  6. Meningitis caused by mumps virus in children admitted to Gorgan’s

    Directory of Open Access Journals (Sweden)

    Meningitis caused by mumps virus in children admitted to Gorgan’s

    2012-01-01

    Full Text Available Background and objectives: Mumps virus is one of the first knowncausative agents of meningitis in children. On-time diagnosis is the firststep in treating meningitis. We aimed to evaluate Mumps virus meningitisin children in Gorgan, IranMaterial and Methods: CSF and blood samples were taken fromchildren with meningitis, Jun 2008 till Sep 2010. For 40 samples withnegative bacterial culture, Extraction of viral RNA was carried out andReal-time PCR was performed for detection of Mumps virus.Demographic, clinical, biochemical and cytological data were collected.We run SPSS version 18 to analyze the data, using Chi Square (p<0.05Results: three (7.5 % samples have Mumps virus, two boys and one girl.All three positive cases have 0.5-1 degrees Celsius fever and vomiting butno bulging fontanel. They have not Kernig, Rodor, Brudzinski’s sign,hepatosplenomegaly, lymphadenopathy, pharyngitis and rash. ESR ishigher than normal in all positive cases and CRP is positive in two cases.Protein of CSF in one case is higher than normal range.Conclusion: meningitis is an emergency condition; therefore, moleculardiagnostic techniques are recommended for early diagnosis andintervention.Key words: meningitis, mumps virus, cerebrospinal fluid, Real-TimePCR

  7. Identification of attenuation markers of a Theileria lestoquardi cell line to be used for the development of live vaccine against malignant ovine theileriosis

    OpenAIRE

    Mousa, Awadia Mohamed Ali Mohamed

    2010-01-01

    Theileria lestoquardi is a tick-borne protozoan parasite and highly pathogenic for sheep. The disease caused by the pathogen is known as malignant ovine theileriosis (MOT) and is transmitted by Hyalomma ticks. Control of the disease can be achieved by immunization of sheep with attenuated T. lestoquardi schizont-infected ovine cells that provides the animal with solid immunity. The approach of using the attenuated vaccine against malignant ovine theileriosis has been carried out successfully ...

  8. Modulation of apoptosis by V protein mumps virus

    Directory of Open Access Journals (Sweden)

    Herrera-Camacho Irma

    2011-05-01

    Full Text Available Abstract Background The Urabe AM9 vaccine strain of mumps virus contains two variants of V protein: VWT (of HN-A1081 viral population and VGly (of HN-G1081. The V protein is a promoting factor of viral replication by blocking the IFN antiviral pathway. Findings We studied the relationship between V protein variants and IFN-α2b-induced apoptosis. V proteins decrease activation of the extrinsic IFN-α2b-induced apoptotic pathway monitored by the caspase 8 activity, being the effect greater with the VWT protein. Both V proteins decrease the activity of caspase 9 of the intrinsic apoptotic pathway. In a system without IFN, the VWT and VGly proteins expression promotes activation of caspases 3 and 7. However, when the cellular system was stimulated with IFN-α, this activity decreased partially. TUNEL assay shows that for treatment with IFN-α and ibuprofen of cervical adenocarcinoma cells there is nuclear DNA fragmentation but the V protein expression reduces this process. Conclusions The reduction in the levels of caspases and DNA fragmentation, suggesting that V protein, particularly VWT protein of Urabe AM9 vaccine strain, modulates apoptosis. In addition, the VWT protein shows a protective role for cell proliferation in the presence of antiproliferative signals.

  9. The live attenuated Actinobacillus pleuropneumoniae triple-deletion mutant ΔapxIC ΔapxIIC ΔapxIV-ORF1 strain, SLW05, Immunizes pigs against lethal challenge with Haemophilus parasuis.

    Science.gov (United States)

    Fu, Shulin; Ou, Jiwen; Zhang, Minmin; Xu, Juan; Liu, Huazhen; Liu, Jinlin; Yuan, Fangyan; Chen, Huanchun; Bei, Weicheng

    2013-02-01

    Haemophilus parasuis and Actinobacillus pleuropneumoniae both belong to the family Pasteurellaceae and are major respiratory pathogens that cause large economic losses in the pig industry worldwide. We previously constructed an attenuated A. pleuropneumoniae serovar 1 live vaccine prototype, SLW05 (ΔapxIC ΔapxIIC ΔapxIV-ORF1), which is able to produce nontoxic but immunogenic ApxIA, ApxIIA, and ApxIVA. This triple-deletion mutant strain was shown to elicit protective immunity against virulent A. pleuropneumoniae. In the present study, we investigated whether immunization with SLW05 could also protect against lethal challenge with virulent H. parasuis SH0165 (serovar 5) or MD0322 (serovar 4). The SLW05 strain was found to elicit a strong humoral antibody response in pigs and to confer significant protection against challenge with a lethal dose of H. parasuis SH0165 or MD0322. IgG subtype analysis revealed that SLW05 induces a bias toward a Th1-type immune response and stimulates interleukin 2 (IL-2) and gamma interferon (IFN-γ) production. Moreover, antisera from SLW05-vaccinated pigs efficiently inhibited both A. pleuropneumoniae and H. parasuis growth in a whole-blood assay. This is the first report that a live attenuated A. pleuropneumoniae vaccine with SLW05 can protect against lethal H. parasuis infection, which provides a novel approach for developing an attenuated H. parasuis vaccine.

  10. Vaccine-Preventable Diseases In Pediatric Patients: A Review Of Measles, Mumps, Rubella, And Varicella.

    Science.gov (United States)

    Levine, Deborah A

    2016-12-01

    Vaccine-preventable diseases such as measles, mumps, rubella, and varicella continue to plague children and adults worldwide. Although public health programs have helped decrease the prevalence and sequelae of these diseases, outbreaks still occur. To limit the spread of these diseases, emergency clinicians must be able to readily identify the characteristic presentations of the rashes associated with measles, rubella, and varicella, as well as the common presenting features associated with mumps. Diagnostic laboratory studies are not usually necessary, as a complete history and physical examination usually lead to an accurate diagnosis. Treatment for these vaccine-preventable diseases usually consists of supportive care, but, in some cases, severe complications and death may occur. This issue provides a review of the clinical features, differential diagnoses, potential complications, and treatment options for measles, mumps, rubella, and varicella.

  11. STUDY ON SEROPREVALENCE OF MUMPS - SPECIFIC IgG ANTIBODIES IN A HEALTHY POPULATION

    Directory of Open Access Journals (Sweden)

    Milena Karcheva

    2010-09-01

    Full Text Available Mumps is a vaccine preventable viral infection. Its typical clinical manifestations are characterized by pain and swelling of the salivary glands, fever, and fatigue. Often other organs are affected - testes in males after puberty (orchitis, ovaries in women (ooforitis, pancreas (pancreatitis, central nervous system (meningities. The use of specific immune prophylaxis led to a significant success in the fight against mumps, but there are still unresolved issues related to the immunological and epidemiological effectiveness of the vaccines. The disease continues to interest researchers today. The main issues being tackled are related to the conduct of virological, clinical and sero-epidemiological studies in different countries. Objectives of the study is to determine the frequency distribution of mumps-specific IgG antibodies in healthy populations in the region of Pleven, Bulgaria. Methods: a cross-sectional sero - epidemiological representative population - based survey in the area was made. Enzyme immunoassay method was used for an indirect proof of mumps - specific IgG serum antibodies. 410 people were examined at an average age of 25 (1 to 84. Of these, 250 (61 % were women and 160 (39 % - men. Results: Of all test results, the negative were 72 (19 %, the borderline were 12 (3 %, the positive were 182 (44 %, and highly positive were 144 (35 %. The vaccination status showed that 242 (69 % of all surveyed were immunized with a vaccine against mumps. According to the immunization schedule in Bulgaria, 132 (33 % people were immunized with monovaccine during the years - 1 intake, 80 (20 % with trivaccine - 1 intake, and 64 (16 % - 2 doses. Conclusion: We believe that despite the specific immunprophylaxis carried out against mumps decades on end, the necessary level of protection leading to its elimination has not yet been reached.

  12. Detection of mumps virus genotype H in two previously vaccinated patients from Mexico City.

    Science.gov (United States)

    Del Valle, Alberto; García, Alí A; Barrón, Blanca L

    2016-06-01

    Infections caused by mumps virus (MuV) have been successfully prevented through vaccination; however, in recent years, an increasing number of mumps outbreaks have been reported within vaccinated populations. In this study, MuV was genotyped for the first time in Mexico. Saliva samples were obtained from two previously vaccinated patients in Mexico City who had developed parotitis. Viral isolation was carried out in Vero cells, and the SH and HN genes were amplified by RT-PCR. Amplicons were sequenced and compared to a set of reference sequences to identify the MuV genotype.

  13. Achieving nanoscale horizontal separations in the standard 2 μm PolyMUMPS process

    KAUST Repository

    Elshurafa, Amro M.

    2013-01-25

    This paper shares with the research community how to achieve, effectively and easily, lateral submicron separations in the standard 2 lm PolyMUMPS process without any fabrication intervention or post-processing, based on the oxide sidewall spacer technique. Thousands of nanoseparations were created and successfully tested by visual inspection and by a simple capacitance measurement. The lateral separations attained were less than 440 nm and reached as low as 280 nm. To corroborate the findings, measurements were performed on different capacitors fabricated in different fabrication runs with consistent results. This is the first time that submicron lateral distances are reported in PolyMUMPS using the oxide spacer technique.

  14. Measles, mumps, and rubella virus vaccine (M-M-R™II): a review of 32 years of clinical and postmarketing experience.

    Science.gov (United States)

    Lievano, Fabio; Galea, Susan A; Thornton, Michele; Wiedmann, Richard T; Manoff, Susan B; Tran, Trung N; Amin, Manisha A; Seminack, Margaret M; Vagie, Kristen A; Dana, Adrian; Plotkin, Stanley A

    2012-11-06

    M-M-R™II (measles, mumps, and rubella virus vaccine live; Merck, Sharp, & Dohme Corp.) is indicated for simultaneous vaccination against measles, mumps, and rubella in individuals ≥ 12 months of age. Before the vaccine era, these viruses infected most exposed individuals, with subsequent morbidity and mortality. One of the greatest achievements of public health has been to eliminate these 3 diseases in large geographic areas. The safety profile of M-M-R™II is described using data from routine global postmarketing surveillance. Postmarketing surveillance has limitations (including incomplete reporting of case data), but allows collection of real-world information on large numbers of individuals, who may have concurrent medical problems excluding them from clinical trials. It can also identify rare adverse experiences (AEs). Over its 32-year history, ≈ 575 million doses of M-M-R™II have been distributed worldwide, with 17,536 AEs voluntarily reported for an overall rate of 30.5 AEs/1,000,000 doses distributed. This review provides evidence that the vaccine is safe and well-tolerated.

  15. Assessment of human immune responses to H7 avian influenza virus of pandemic potential: results from a placebo-controlled, randomized double-blind phase I study of live attenuated H7N3 influenza vaccine.

    Directory of Open Access Journals (Sweden)

    Larisa Rudenko

    Full Text Available INTRODUCTION: Live attenuated influenza vaccines (LAIVs are being developed to protect humans against future epidemics and pandemics. This study describes the results of a double-blinded randomized placebo-controlled phase I clinical trial of cold-adapted and temperature sensitive H7N3 live attenuated influenza vaccine candidate in healthy seronegative adults. OBJECTIVE: The goal of the study was to evaluate the safety, tolerability, immunogenicity and potential shedding and transmission of H7N3 LAIV against H7 avian influenza virus of pandemic potential. METHODS AND FINDINGS: Two doses of H7N3 LAIV or placebo were administered to 40 randomly divided subjects (30 received vaccine and 10 placebo. The presence of influenza A virus RNA in nasal swabs was detected in 60.0% and 51.7% of subjects after the first and second vaccination, respectively. In addition, vaccine virus was not detected among placebo recipients demonstrating the absence of person-to-person transmission. The H7N3 live attenuated influenza vaccine demonstrated a good safety profile and was well tolerated. The two-dose immunization resulted in measurable serum and local antibody production and in generation of antigen-specific CD4⁺ and CD8⁺ memory T cells. Composite analysis of the immune response which included hemagglutinin inhibition assay, microneutralization tests, and measures of IgG and IgA and virus-specific T cells showed that the majority (86.2% of vaccine recipients developed serum and/or local antibodies responses and generated CD4⁺ and CD8⁺ memory T cells. CONCLUSIONS: The H7N3 LAIV was safe and well tolerated, immunogenic in healthy seronegative adults and elicited production of antibodies broadly reactive against the newly emerged H7N9 avian influenza virus. TRIAL REGISTRATION: ClinicalTrials.gov NCT01511419.

  16. 75 FR 48715 - Proposed Vaccine Information Materials for Measles, Mumps, Rubella, and Varicella Vaccines

    Science.gov (United States)

    2010-08-11

    ... HUMAN SERVICES Centers for Disease Control and Prevention Proposed Vaccine Information Materials for Measles, Mumps, Rubella, and Varicella Vaccines AGENCY: Centers for Disease Control and Prevention (CDC... National Childhood Vaccine Injury Act (NCVIA) (42 U.S.C. 300aa-26), the CDC must develop vaccine...

  17. Retinopathy following measles, mumps, and rubella vaccination in an immuno-incompetent girl

    NARCIS (Netherlands)

    Schuil, J.; van de Putte, E.M.; Zwaan, C.M.; Koole, F.D.; Meire, F.M.

    1998-01-01

    We describe a 4-year-old girl with subnormal visual acuity due to a bilateral retinopathy. The child had a history of encephalitis following MMR vaccination. Temporary retinopathy associated with measles, mumps, and rubella (MMR) vaccination has been described. Recently an idiopathic CD4+ T

  18. A population-based study of measles, mumps and rubella vaccination and autism

    DEFF Research Database (Denmark)

    Madsen, Kreesten Meldgaard; Hviid, Anders; Vestergaard, Mogens

    2002-01-01

    Background It has been suggested that vaccination against measles, mumps, and rubella (MMR) is a cause of autism. Methods We conducted a retrospective cohort study of all children born in Denmark from January 1991 through December 1998. The cohort was selected on the basis of data from the Danish...

  19. Mumps Parotitis and Ovarian Cancer: Modern Significance of an Historic Association

    Science.gov (United States)

    2009-10-01

    parotitis and subsequent development of ovarian cancer. On June of 2009, we searched MEDLINE (via PubMed), Web of Science and EMBASE using the...association between history of mumps parotitis and subsequent development of ovarian cancer. On June of 2009, we searched MEDLINE (via PubMed), Web of Science and

  20. The effects of pegylated interferon--alpha2B on mumps orchitis.

    Science.gov (United States)

    Pal, Goutam

    2013-09-01

    To evaluate the effects of pegylated Interferon--alpha2B on mumps orchitis, 80 patients suffering from mumps orchitis, were randomly assigned into 2 groups of 40 patients each. In the first group patients received pegylated interferon--alpha2B and the other group did not, acting as controls. All were confirmed by mumps IgM (ELISA) and evaluated by testis size, semen analysis and hormone level. In the first group, the symptoms resolved within average 2.2 days and testicular size returned to normal within average 5.3 days but in 2nd group, those returned to normal within average 5.7 days and 10.2 days respectively. In the 1st group, oligospermia was detected in 11 patients and subsequently returned to normal in all patients and there was no testicular atrophy. In the 2nd group oligospermia was detected in 13 patients and were persistently low in 3 patients and testicular atrophy detected in 2 patients. The results indicated the beneficial role of pegylated interferon--alpha2B in preventing infertility from mumps orchitis.

  1. Retinopathy following measles, mumps, and rubella vaccination in an immuno-incompetent girl

    NARCIS (Netherlands)

    Schuil, J.; van de Putte, E.M.; Zwaan, C.M.; Koole, F.D.; Meire, F.M.

    1998-01-01

    We describe a 4-year-old girl with subnormal visual acuity due to a bilateral retinopathy. The child had a history of encephalitis following MMR vaccination. Temporary retinopathy associated with measles, mumps, and rubella (MMR) vaccination has been described. Recently an idiopathic CD4+ T lymphocy

  2. Anesthesia mumps resulting in temporary facial nerve paralysis after the auditory brainstem implantation in a 3-year-old child.

    Science.gov (United States)

    Özdek, Ali; Bayır, Ömer; Işık, Murat Eray; Tatar, Emel Çadallı; Saylam, Güleser; Korkmaz, Hakan

    2014-01-01

    An acute transient sialadenitis of the major salivary glands in the early postoperative period is called 'anesthesia mumps'. It has been reported in different surgical procedures especially in neurosurgical procedures. Anesthesia mumps develops very fast after the extubation period but it usually regresses with no sequelae within a few hours. However, sometimes serious complication can occur such as respiratory distress. In this report, we present a 3-year-old girl with an anesthesia mumps and facial palsy occurring after successful auditory brainstem implantation and we discuss the cause and the management of this rare complication in this report.

  3. Attenuation and Immunogenicity of a Live High Pathogenic PRRSV Vaccine Candidate with a 32-Amino Acid Deletion in the nsp2 Protein

    Directory of Open Access Journals (Sweden)

    Wenhui Lu

    2014-01-01

    Full Text Available A porcine reproductive and respiratory syndrome virus (PRRSV QY1 was serially passed on Marc-145 cells. Virulence of different intermediate derivatives of QY1 (P5, P60, P80, and P100 were determined. The study found that QY1 had been gradually attenuated during the in vitro process. Pathogenicity study showed that pigs inoculated with QY1 P100 and P80 did not develop any significant PRRS clinic symptoms. However, mild-to-moderate clinical signs and acute HP-PRRSV symptoms of infection were observed in pigs inoculated with QY1 P60 and P5, respectively. Furthermore, we determined the whole genome sequences of these four intermediate viruses. The results showed that after 100 passages, compared to QY1 P5, a total of 32 amino acid mutations were found. Moreover, there were one nucleotide deletion and a unique 34-amino acid deletion found at 5′UTR and in nsp2 gene during the attenuation process, respectively. Such deletions were genetically stable in vivo. Following PRRSV experimental challenge, pigs inoculated with a single dose of QY1 P100 developed no significant clinic symptoms and well tolerated lethal challenge, while QY1 P80 group still developed mild fever in the clinic trial after challenge. Thus, we concluded that QY1 P100 was a promising and highly attenuated PRRSV vaccine candidate.

  4. Comparison of the live-attenuated Japanese encephalitis vaccine SA14-14-2 strain with its pre-attenuated virulent parent SA14 strain: similarities and differences in vitro and in vivo.

    Science.gov (United States)

    Yun, Sang-Im; Song, Byung-Hak; Polejaeva, Irina A; Davies, Christopher J; White, Kenneth L; Lee, Young-Min

    2016-10-01

    Japanese encephalitis virus (JEV) is the main cause of acute viral encephalitis, primarily affecting children and young adults in the Asia-Pacific region. JEV is a vaccine-preventable pathogen, with four types of JE vaccine licensed in different regions of the world. To date, the most common JEV strain used in vaccine development and production is SA14-14-2, an attenuated strain derived from its wild-type parental strain SA14. In this study, we directly compared the phenotypic and genotypic characteristics of SA14 and SA14-14-2 to determine the biological and genetic properties associated with their differential virulence. In susceptible BHK-21 cells, SA14-14-2 grew slightly more slowly and formed smaller plaques than SA14, but unlike SA14, it showed almost no expression of the viral protein NS1', the product of a conserved predicted RNA pseudoknot-mediated ribosomal frameshift. In weanling ICR mice, SA14-14-2 was highly attenuated in terms of both neuroinvasiveness and neurovirulence, with its median lethal doses invariably over five logs higher than those of SA14 when inoculated intramuscularly and intracerebrally. Interestingly, the neurovirulence of SA14-14-2 was dependent on mouse age, with the 1- to 7-day-old mice being highly susceptible and the 14- to 21-day-old mice becoming resistant to intracerebral inoculation. At the genome level, SA14-14-2 differed from SA14 by 57 nucleotides, including one silent G-to-A substitution at position 3599 within the predicted RNA pseudoknot for NS1' synthesis; of the 57 differences, 25 resulted in amino acid substitutions. Our data pave the way for the development of new genetically modified JE vaccines.

  5. 牛病毒性腹泻病二价弱毒活疫苗制备工艺研究%Study on Preparation Technique of Divalent Attenuated Virus Live Vaccine of Bovine Viral Diarrhea Virus

    Institute of Scientific and Technical Information of China (English)

    李海涛; 苗利光; 刘艳环; 朱言柱; 安亚雄; 王坤; 冯卓

    2013-01-01

    研究了BVDV2/JZ05-1和BVDV1/JZ05-3二价弱毒活疫苗的制备工艺.通过对BVDV2/JZ05-1和BVDV1/JZ05-3疫苗毒传代培养测定毒价后,试制出5批毒价分别是10.4TCID50/mL和105.6TCID50/mL的BVDV二价弱毒活疫苗,经检验符合试验设计要求.%The aim of this study was to explore the preparation technique of divalent attenuated virus live vaccine of bovine viral diarrhea virus 2/JZ05-1(BVDV2/JZ05-1) and BVDV1/JZ05-3.BVDV2/JZ05-1 and BVDV1/JZ05-3 were continuously cultivated in cell culture.The poison titor was examined.5 groups of divalent attenuated BVDV live vaccine were produced.The poison prices were 105.4TCID50/mL and 105.6TCID50/mL,respectively.The vaccines were examined and was within the range of the test design requirement.

  6. Investigation of a mumps outbreak in Mongolia, January to April 2011

    Directory of Open Access Journals (Sweden)

    Dapeng Luo

    2012-12-01

    Full Text Available Introduction: The Gurvantes district in Omnogovi Province reported a suspected mumps outbreak to the Mongolia Ministry of Health in March 2011. An outbreak investigation team was established to verify the diagnosis and to determine the magnitude of the outbreak.Methods: The descriptive study comprised retrospective investigation of local hospital medical records and surveillance data, and interviews with school teachers, doctors, probable cases and their close contacts. The World Health Organization standard case definition was used to define mumps cases. Clinical specimens were collected for laboratory confirmation.Results: There were 153 cases, none under two years of age, with the five- to 14-years-old age group having the highest rates. There was no difference by sex (P = 0.12. A single index case appeared to be the source of the outbreak, and there were four outbreak waves. Of the 129 cases with information on epidemiological links, 94 (72.3% were linked to other cases at a kindergarten or school, 17 (13% were from secondary spread of family members, two (1.5% were from secondary spread of other relatives, and 16 had no established links. Eight cases (5.2% were confirmed through laboratory investigation.Conclusion: This was the first high-magnitude mumps outbreak since the introduction of the measles-mumps-rubella vaccine in Mongolia in September 2009. There were no cases among vaccinated children; cases were seen among older children and adults not eligible for the vaccine. This suggests that immunity to mumps is still low in Mongolia. Future outbreaks may occur among this unvaccinated population.

  7. The Live Attenuated Cholera Vaccine CVD 103-HgR Primes Responses to the Toxin-Coregulated Pilus Antigen TcpA in Subjects Challenged with Wild-Type Vibrio cholerae.

    Science.gov (United States)

    Mayo-Smith, Leslie M; Simon, Jakub K; Chen, Wilbur H; Haney, Douglas; Lock, Michael; Lyon, Caroline E; Calderwood, Stephen B; Kirkpatrick, Beth D; Cohen, Mitchell; Levine, Myron M; Gurwith, Marc; Harris, Jason B

    2017-01-01

    One potential advantage of live attenuated bacterial vaccines is the ability to stimulate responses to antigens which are only expressed during the course of infection. To determine whether the live attenuated cholera vaccine CVD 103-HgR (Vaxchora) results in antibody responses to the in vivo-induced toxin-coregulated pilus antigen TcpA, we measured IgA and IgG responses to Vibrio cholerae O1 El Tor TcpA in a subset of participants in a recently reported experimental challenge study. Participants were challenged with V. cholerae O1 El Tor Inaba N16961 either 10 days or 90 days after receiving the vaccine or a placebo. Neither vaccination nor experimental infection with V. cholerae alone resulted in a robust TcpA IgG or IgA response, but each did elicit a strong response to cholera toxin. However, compared to placebo recipients, vaccinees had a marked increase in IgG TcpA antibodies following the 90-day challenge, suggesting that vaccination with CVD 103-HgR resulted in priming for a subsequent response to TcpA. No such difference between vaccine and placebo recipients was observed for volunteers challenged 10 days after vaccination, indicating that this was insufficient time for vaccine-induced priming of the TcpA response. The priming of the response to TcpA and potentially other antigens expressed in vivo by attenuated V. cholerae may have relevance to the maintenance of immunity in areas where cholera is endemic.

  8. A Live Attenuated Equine Infectious Anemia Virus Proviral Vaccine with a Modified S2 Gene Provides Protection from Detectable Infection by Intravenous Virulent Virus Challenge of Experimentally Inoculated Horses

    Science.gov (United States)

    Li, Feng; Craigo, Jodi K.; Howe, Laryssa; Steckbeck, Jonathan D.; Cook, Sheila; Issel, Charles; Montelaro, Ronald C.

    2003-01-01

    Previous evaluations of inactivated whole-virus and envelope subunit vaccines to equine infectious anemia virus (EIAV) have revealed a broad spectrum of efficacy ranging from highly type-specific protection to severe enhancement of viral replication and disease in experimentally immunized equids. Among experimental animal lentivirus vaccines, immunizations with live attenuated viral strains have proven most effective, but the vaccine efficacy has been shown to be highly dependent on the nature and severity of the vaccine virus attenuation. We describe here for the first time the characterization of an experimental attenuated proviral vaccine, EIAVUKΔS2, based on inactivation of the S2 accessory gene to down regulate in vivo replication without affecting in vitro growth properties. The results of these studies demonstrated that immunization with EIAVUKΔS2 elicited mature virus-specific immune responses by 6 months and that this vaccine immunity provided protection from disease and detectable infection by intravenous challenge with a reference virulent biological clone, EIAVPV. This level of protection was observed in each of the six experimental horses challenged with the reference virulent EIAVPV by using a low-dose multiple-exposure protocol (three administrations of 10 median horse infectious doses [HID50], intravenous) designed to mimic field exposures and in all three experimentally immunized ponies challenged intravenously with a single inoculation of 3,000 HID50. In contrast, naïve equids subjected to the low- or high-dose challenge develop a detectable infection of challenge virus and acute disease within several weeks. Thus, these data demonstrate that the EIAV S2 gene provides an optimal site for modification to achieve the necessary balance between attenuation to suppress virulence and replication potential to sufficiently drive host immune responses to produce vaccine immunity to viral exposure. PMID:12805423

  9. Regulated delayed expression of rfc enhances the immunogenicity and protective efficacy of a heterologous antigen delivered by live attenuated Salmonella enterica vaccines.

    Science.gov (United States)

    Kong, Qingke; Liu, Qing; Jansen, Angela M; Curtiss, Roy

    2010-08-23

    The Salmonella rfc gene encodes the O-antigen polymerase. We constructed three strains in which we replaced the native rfc promoter with the arabinose-dependent araC P(BAD) promoter so that rfc expression was dependent on exogenously supplied arabinose provided during in vitro growth. The three mutant strains were designed to synthesize different amounts of Rfc by altering the ribosome-binding sequence and start codon. We examined these strains for a number of in vitro characteristics compared to an isogenic Deltarfc mutant and the wild-type parent strain. One promoter-replacement mutation, DeltaP(rfc174), yielded an optimal profile, exhibiting wild-type characteristics when grown with arabinose, and Deltarfc characteristics when grown without arabinose. In addition, when administered orally, the DeltaP(rfc174) strain was completely attenuated in for virulence in mice. The DeltaP(rfc174) mutation was introduced into attenuated Salmonella vaccine strain chi9241 (DeltapabA DeltapabB DeltaasdA) followed by introduction of an Asd(+) balanced-lethal plasmid to designed for expression of the pneumococcal surface protein PspA. Mice immunized with either chi9241 or its DeltaP(rfc174) derivative expressing pspA were protected against S. pneumoniae challenge.

  10. Live vaccine against measles, mumps, and rubella and the risk of hospital admissions for nontargeted infections

    DEFF Research Database (Denmark)

    Sørup, Signe; Benn, Christine Stabell; Poulsen, Anja

    2014-01-01

    ). Nationwide Danish registers provided data on vaccinations and hospital admissions. The recommended vaccination schedule was inactivated vaccine against diphtheria, tetanus, pertussis, polio, and Haemophilus influenzae type b (DTaP-IPV-Hib) administered at ages 3, 5, and 12 months and MMR at age 15 months...

  11. Seroprevalence of mumps in The Netherlands: dynamics over a decade with high vaccination coverage and recent outbreaks.

    Directory of Open Access Journals (Sweden)

    Gaby Smits

    Full Text Available Here we present mumps virus specific antibody levels in a large cross-sectional population-based serosurveillance study performed in the Netherlands in 2006/2007 (n = 7900. Results were compared with a similar study (1995/1996 and discussed in the light of recent outbreaks. Mumps antibodies were tested using a fluorescent bead-based multiplex immunoassay. Overall seroprevalence was 90.9% with higher levels in the naturally infected cohorts compared with vaccinated cohorts. Mumps virus vaccinations at 14 months and 9 years resulted in an increased seroprevalence and antibody concentration. The second vaccination seemed to be important in acquiring stable mumps antibody levels in the long term. In conclusion, the Dutch population is well protected against mumps virus infection. However, we identified specific age- and population groups at increased risk of mumps infection. Indeed, in 2007/2008 an outbreak has occurred in the low vaccination coverage groups emphasizing the predictive value of serosurveillance studies.

  12. Absence of an N-Linked Glycosylation Motif in the Glycoprotein of the Live-Attenuated Argentine Hemorrhagic Fever Vaccine, Candid #1, Results in Its Improper Processing, and Reduced Surface Expression

    Science.gov (United States)

    Manning, John T.; Seregin, Alexey V.; Yun, Nadezhda E.; Koma, Takaaki; Huang, Cheng; Barral, José; de la Torre, Juan C.; Paessler, Slobodan

    2017-01-01

    Junin virus (JUNV), a highly pathogenic New World arenavirus, is the causative agent of Argentine hemorrhagic fever (AHF). The live-attenuated Candid #1 (Can) strain currently serves as a vaccine for at-risk populations. We have previously shown that the Can glycoprotein (GPC) gene is the primary gene responsible for attenuation in a guinea pig model of AHF. However, the mechanisms through which the GPC contributes to the attenuation of the Can strain remain unknown. A more complete understanding of the mechanisms underlying the attenuation and immunogenicity of the Can strain will potentially allow for the rational design of additional safe and novel vaccines. Here, we provide a detailed comparison of both RNA and protein expression profiles between both inter- and intra-segment chimeric JUNV recombinant clones expressing combinations of genes from the Can strain and the pathogenic Romero (Rom) strain. The recombinant viruses that express Can GPC, which were shown to be attenuated in guinea pigs, displayed different RNA levels and GPC processing patterns as determined by Northern and Western blot analyses, respectively. Analysis of recombinant viruses containing amino acid substitutions selected at different mouse brain passages during the generation of Can revealed that altered Can GPC processing was primarily due to the T168A substitution within G1, which eliminates an N-linked glycosylation motif. Incorporation of the T168A substitution in the Rom GPC resulted in a Can-like processing pattern of Rom GPC. In addition, JUNV GPCs containing T168A substitution were retained within the endoplasmic reticulum (ER) and displayed significantly lower cell surface expression than wild-type Rom GPC. Interestingly, the reversion A168T in Can GPC significantly increased GPC expression at the cell surface. Our results demonstrate that recombinant JUNV (rJUNV) expressing Can GPC display markedly different protein expression and elevated genomic RNA expression when compared to

  13. 三种国产甲型肝炎减毒活疫苗的免疫学效果比较%Comparative Study on the Immune Effects of Three Kinds of China-made Live Attenuated Hepatitis A Vaccines

    Institute of Scientific and Technical Information of China (English)

    张世勇; 刘新力; 丁月新; 夏建玲; 侯通; 张勇

    2001-01-01

    为考核并比较甲型肝炎减毒活疫苗(甲肝疫苗)的免疫学效果,对314名易感儿童随机分为3组,分别接种市售昆明、杭州、长春3个厂家生产的甲肝疫苗,免疫后21、34天采血检测抗-HAV。结果显示:免疫后21天3个厂家甲肝疫苗抗-HAV阳转率分别为61.9%、60.9%和80.0%,免疫后34天分别为71.6%、66.7%和44.9%,国产高滴度甲肝疫苗安全性好,但疫苗质量有待进一步提高,以获得更好的免疫学效果。%To evaluate and compare the immune effects of three kinds of domestic live attenuated hepatits A vaccines, 314 anti-hepatitis A virus(HAV)antibody negative children were randomly divided into 3 groups and vaccinated with commercial live attenuated hepatitis A vaccines made in Kunming, Hangzhou and Changchun respectively. Serum samples collected 21 and 34 days after inoculation were tested for anti-HAV. The vaccines produced in 3 factories all had a similar positive seroconversion rates of 61.9%, 60.9% and 80.0% 21 days after, vaccination and a significantly differential rates of 71.6%, 66.7% and 44.9% 34 days after. The results suggested that China-made live attenuated hepatits A vaccine with higher titer is safe, but the quality need to be improved to get a better immune efficacy.

  14. Viral Inhibition of the IFN-Induced JAK/STAT Signalling Pathway: Development of Live Attenuated Vaccines by Mutation of Viral-Encoded IFN-Antagonists

    Directory of Open Access Journals (Sweden)

    Stephen B. Fleming

    2016-06-01

    Full Text Available The interferon (IFN induced anti-viral response is amongst the earliest and most potent of the innate responses to fight viral infection. The induction of the Janus kinase/signal transducer and activation of transcription (JAK/STAT signalling pathway by IFNs leads to the upregulation of hundreds of interferon stimulated genes (ISGs for which, many have the ability to rapidly kill viruses within infected cells. During the long course of evolution, viruses have evolved an extraordinary range of strategies to counteract the host immune responses in particular by targeting the JAK/STAT signalling pathway. Understanding how the IFN system is inhibited has provided critical insights into viral virulence and pathogenesis. Moreover, identification of factors encoded by viruses that modulate the JAK/STAT pathway has opened up opportunities to create new anti-viral drugs and rationally attenuated new generation vaccines, particularly for RNA viruses, by reverse genetics.

  15. Energy release, beam attenuation radiation damage, gas production and accumulation of long-lived activity in Pb, Pb-Bi and Hg targets

    Energy Technology Data Exchange (ETDEWEB)

    Shubin, Yu.N. [IPPE, Obninsk (Russian Federation)

    1996-06-01

    The calculation and analysis of the nuclei concentrations and long-lived residual radioactivity accumulated in Pb, Pb-Bi and Hg targets irradiated by 800 MeV, 30 mA proton beam have been performed. The dominating components to the total radioactivity of radionuclides resulting from fission and spallation reactions and radiative capture by both target nuclei and accumulated radioactive nuclei for various irradiation and cooling times were analyzed. The estimations of spectral component contributions of neutron and proton fluxes to the accumulated activity were carried out. The contributions of fission products to the targets activity and partial activities of main long-lived fission products to the targets activity and partial activities of main long-lived fission products were evaluated. The accumulation of Po isotopes due to reactions induced by secondary alpha-particles were found to be important for the Pb target as compared with two-step radiative capture. The production of Tritium in the targets and its contribution to the total targets activity was considered in detail. It is found that total activities of both targets are close to one another.

  16. 首次接种乙型脑炎减毒活疫苗引起小儿高热1例%High fever in children following live attenuated Japanese encephalitis first-time vaccination: a case report

    Institute of Scientific and Technical Information of China (English)

    王筱婧; 左艳敏; 吴婷婷; 田硕

    2011-01-01

    One case of child fever cause by live attenuated Japanese encephalitis vaccine was reported and analyzed in this study. The temperature of the child patient was attempted to 39.3℃. After treating with paracetamol and physical cooling, the patient's temperature was fallen to normal.%本文对1例首次接种乙型脑炎减毒活疫苗后引起小儿高热的不良反应进行了报道.患儿体温达到39.3℃,口服给予泰诺林及进行物理降温治疗后,患儿体温恢复正常,情况好转.

  17. 麻疹减毒活疫苗强化免疫策略及其应用%Strategy and Application of Measles Attenuated Live Vaccine Supplementary Immunization Activity

    Institute of Scientific and Technical Information of China (English)

    张倩

    2010-01-01

    麻疹减毒活疫苗(Measles Attenuated Live Vaccine,MV)强化免疫活动(Supplementary Immunization Activities,SIA)作为消除麻疹的主要策略之一,为未免疫和免疫不成功的人群提供第二次MV接种的机会,不论既往有无含麻疹成分疫苗(Measles-containing Vaccine,MCV)的免疫史和麻疹患病史,均为目标人群,再接种1剂MV.现就国内外开展MV SIA的接种率、抗体水平、疑似预防接种异常反应、SIA后麻疹发病率等方面进行简要综述.

  18. 贵州省流行性乙型脑炎疫苗强化免疫成本效益评价%Cost-effectiveness evaluation on Japanese Encephalitis Live Attenuated Vaccine Mass Immunization Campaign in Guizhou

    Institute of Scientific and Technical Information of China (English)

    张丽; 詹玮; 蒋凤; 芮丽萍; 刘铭; 刁壁; 尹遵栋; 李艺星; 罗会明

    2012-01-01

    OBJECTIVE To review the economic benefits of Japanese Encephalitis ( JE) live attenuated vaccine mass campaign in Guizhou province. METHODS Data from the sampling were analyzed by cost—effectiveness analysis to investigate the expenditure of hospitalization and non—hospital treatment, chaperone costs and re—habilitation costs. The per capita Gross Domestic Product was created by the nursing personnel of JE cases as well as the expenditure, which was essential for controlling JE. The index DALY, which was commonly applied internationally at present, was utilized to calculate the loss of death and disability caused by the incidence of JE quantitatively. Also, the ratio of cost-effectiveness and net benefits produced were counted. RESULTS After JE live attenuated vaccine mass immunization campaigns, the annual average incidence rate of JE in Guizhou province decreased by 65.30% than 1990-2006. Meanwhile, the reduced loss of incidence, disability and death amount to 843.6 thousand Yuan. The net benefits produced were 125.20 million Yuan and the rate of cost-effectiveness was 1: 4.88. CONCLUSION All of the data indicate that the incidence of JE decreased remarkably after the mass immunization campaign with JE live attenuated vaccine. The measure of preventing JE by using JE live attenuated vaccine is economical and effectively.%目的 探讨贵州省实施流行性乙型脑炎(乙脑)疫苗强化免疫的成本效益.方法 抽样调查乙脑病例住院和非住院治疗费用、陪护费用、康复费用以及乙脑疫苗强化免疫工作中需投入的经费.计算因乙脑患病陪护人员人均减少的产值,用伤残调整寿命年指标(DALY)计算因乙脑发病造成的死亡和伤残损失,采用成本-效益分析方法,计算乙脑强化免疫的成本效益比值和产生的净效益.结果 1例乙脑病例患病后社会减少产值84.36万元.贵州省2007年开展乙脑疫苗强化免疫后发病率较1990~2006年强化前平均下降了65

  19. Screening and application of gelatin-free stabilizer for live attenuated varicella vaccine%水痘减毒活疫苗无明胶稳定剂的筛选和应用

    Institute of Scientific and Technical Information of China (English)

    马相虎; 沈谊清; 杨月莲; 陈哲文; 程鹏飞; 王亮

    2014-01-01

    Objective To develope new gelatin-free stabilizers in order to improve the safety of live attenuated varicella vaccine,Methods Based on the current stabilizer formula of live attenuated varicella vaccine,four new stabilizers (B,C,D,E formulas) were formulated by removing gelatin.Vaccines without gelatin (B,C,D,E vaccines) were prepared with the formulated gelatin-free stabilizers and compared with the current live attenuated varicella vaccine with gelatin (A vaccine as control).The optimized stabilizer formula was determined.Results After 7 days at 37 ℃,the relevant qualities of all vaccines conformed with the requirement of Registration Criteria of Live Attenuated Vaccine Varicella,and the virus titers of A,B,C,D,E vaccines were 3.6,3.5,3.3,3.3 and 3.3 lgPFU/0.5 ml,respectively,but the virus titers of C,D,E vaccines have dropped to critical value.After 24 months at 2-8 ℃,the virus titers of A,B,C,D,E vaccines were 3.4,3.4,3.2,3.0 and 2.8 lgPFU/0.5 ml,respectively.Among the four vaccines without gelatin,the virus titers of C,D,E vaccines have been below the requirement (3.3 lgPFU/0.5 ml),only B vaccine met the requirement and was the same as A vaccine.Conclusion The B formula stabilizer without gelatin has better protection for varicella virus.%目的 研制不含明胶的新型稳定剂,以提高水痘减毒活疫苗的安全性.方法 以现行水痘减毒活疫苗稳定剂配方为基础,去除明胶,配制4种不同的新型稳定剂(B、C、D、E配方).用无明胶稳定剂制备水痘减毒活疫苗,并将制备的无明胶稳定剂疫苗(B、C、D、E疫苗)与现行的含明胶稳定剂疫苗(作为对照的A疫苗)进行比较,确定最佳稳定剂配方.结果 疫苗成品于37℃放置7d后,A、B、C、D、E疫苗的相关质量指标均符合《水痘减毒活疫苗注册标准》的要求,病毒滴度分别为3.6、3.5、3.3、3.3、3.3 lgPFU/0.5 ml,但C、D、E疫苗的病毒滴度已降至临界值.疫苗成品于2~8℃放置24个月后,A、B

  20. Oral vaccination with LcrV from Yersinia pestis KIM delivered by live attenuated Salmonella enterica serovar Typhimurium elicits a protective immune response against challenge with Yersinia pseudotuberculosis and Yersinia enterocolitica.

    Science.gov (United States)

    Branger, Christine G; Torres-Escobar, Ascención; Sun, Wei; Perry, Robert; Fetherston, Jacqueline; Roland, Kenneth L; Curtiss, Roy

    2009-08-27

    The use of live recombinant attenuated Salmonella vaccines (RASV) synthesizing Yersinia proteins is a promising approach for controlling infection by Yersinia species. In this study, we constructed attenuated Salmonella strains which synthesize a truncated form of LcrV, LcrV196 and evaluated the immune response and protective efficacy elicited by these strains in mice against two other major species of Yersinia: Yersinia pseudotuberculosis and Yersinia enterocolitica. Surprisingly, we found that the RASV strain alone was sufficient to afford nearly full protection against challenge with Y. pseudotuberculosis, indicating the likelihood that Salmonella produces immunogenic cross-protective antigens. In contrast, lcrV196 expression was required for protection against challenge with Y. enterocolitica strain 8081, but was not sufficient to achieve significant protection against challenge with Y. enterocolitica strain WA, which expressed a divergent form of lcrV. Nevertheless, we are encouraged by these findings to continue pursuing our long-term goal of developing a single vaccine to protect against all three human pathogenic species of Yersinia.

  1. Influenza vaccine concurrently administered with a combination measles, mumps, and rubella vaccine to young children.

    Science.gov (United States)

    Lum, Lucy Chai See; Borja-Tabora, Charissa Fay; Breiman, Robert F; Vesikari, Timo; Sablan, Benjamin P; Chay, Oh Moh; Tantracheewathorn, Taweewong; Schmitt, Heinz-Josef; Lau, Yu-Lung; Bowonkiratikachorn, Piyaporn; Tam, John S; Lee, Bee Wah; Tan, Kah Kee; Pejcz, Jerzy; Cha, Sungho; Gutierrez-Brito, Maricruz; Kaltenis, Petras; Vertruyen, Andre; Czajka, Hanna; Bojarskas, Jurgis; Brooks, W Abdullah; Cheng, Sheau-Mei; Rappaport, Ruth; Baker, Sherryl; Gruber, William C; Forrest, Bruce D

    2010-02-10

    Children aged 11 to vaccine (LAIV) or placebo, 35+/-7 days apart. Dose 1 was administered concomitantly with a combined measles, mumps, and rubella vaccine (Priorix). Seroresponses to measles and mumps were similar between groups. Compared with placebo, response rates to rubella in LAIV+Priorix recipients were statistically lower at a 15 IU/mL threshold (83.9% vs 78.0%) and the prespecified noninferiority criteria were not met. In a post hoc analysis using an alternate widely accepted threshold of 10 IU/mL, the noninferiority criteria were met (93.4% vs 89.8%). Concomitant administration with Priorix did not affect the overall influenza protection rate of LAIV (78.4% and 63.8% against antigenically similar influenza strains and any strain, respectively).

  2. Are there altered antibody responses to measles, mumps, or rubella viruses in autism?

    Science.gov (United States)

    Libbey, Jane E; Coon, Hilary H; Kirkman, Nikki J; Sweeten, Thayne L; Miller, Judith N; Lainhart, Janet E; McMahon, William M; Fujinami, Robert S

    2007-06-01

    The role that virus infections play in autism is not known. Others have reported that antibodies against measles virus are higher in the sera/plasma of children with autism versus controls. The authors investigated antibody titers to measles, mumps, and rubella viruses and diphtheria toxoid in children with autism, both classic onset (33) and regressive onset (26) forms, controls (25, healthy age- and gender-matched) and individuals with Tourette's syndrome (24) via enzyme-linked immunosorbent assays. No significant differences in antibody titers to measles, mumps, and rubella viruses and diphtheria toxoid were found among the four groups. Additionally, there were no significant differences between the four groups for total immunoglobulin (Ig)G or IgM. Interestingly, the authors did find a significant number (15/59) of autism subjects (classic and regressive onset combined) who had a very low or no antibody titer against rubella virus, compared to a combine control/Tourette's group (2/49).

  3. Mumps in a district primary school at the locality of Santa Fe, Bogota (Colombia 2010.

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    Oneida Castañeda

    2010-12-01

    Full Text Available Background. Epidemic parotitis (“mumps” is a human viral infection which affects mainly the salivary glands; its peak incidence afflicts children 5 to 9-year. At epidemiologic week (EW 40/2010, the Centro Oriente II Level Hospital received a community report about a mumps outbreak in a District Primary School (DPS, eastwards of the locality of Santa Fe (Bogotá. The hospital’s epidemiology office sent a response team to investigate the situation and to guide prevention & control actions. Methods. The team made an outbreak descriptive study; field investigation included description time-place-person; case-definition as patient with active clinical condition of parotitis; Active Institutional Search (AIS and house visitations; study variables matched those of the official individual notification report. Data were registered and analyzed using Epi -Info 3.5.1® with frequency, central trend and association measurements. Results. 14 mumps cases were identified: 1 adult and 13(93% children; 5(35,7% were girls; median age was 11,9 year (range 7-40. Four cases (28,6% were confirmed by clinical signs, 10(71,4% by epidemiologic link; no one was hospitalized. 12 patients (86% had unknown vaccination status; 11 cases (78% produced neither the vaccination card nor any additional information. Index case occurred at EW30/2010 and the epidemic peak occurred at EW34/2010; attack rate was 8.1%. Conclusions. Epidemiology office confirmed mumps outbreak, delayed notification and impossibility to verify vaccination records. The response team recommended the DPS to strengthen biosafety measures; and advised local health institution to increase epidemiologic surveillance & control activities, adherence to national mumps protocol, school vaccination and to promote information, communication, education strategies on importance of vaccination and cards right use.

  4. [An outbreak of mumps in a high school: Estimation of vaccine effectiveness. Zaragoza 2011].

    Science.gov (United States)

    Compés-Dea, Cecilia; Guimbao-Bescós, Joaquín; Gaspar-Escayola, José Ignacio; Lázaro-Belanche, María Ángeles; Aznar-Brieba, Amaya

    2015-01-01

    Mumps outbreaks continue to occur, even after the consolidation of vaccination programs. An outbreak of mumps occurred in a high school in Zaragoza during December 2011. To describe the outbreak and estimate vaccine effectiveness. unilateral or bilateral swelling of the parotid or other salivary glands for three or more days without any other apparent cause. People attending the 'Parque Goya' High School or with transmission chain origin in the High School. From two days before the onset of symptoms of the first case to five days after the last case. Samples were collected for virus confirmation (IgM, urine culture and oropharyngeal exudate), and isolates were processed for genotyping. A retrospective cohort study was performed in two high school classrooms to estimate vaccine efficacy. Public health authorities conducted active surveillance, isolation of cases, and vaccination of susceptible contacts. There were 27 cases. Twenty-one (77.8%) were vaccinated with two doses of Measles-Mumps-Rubella vaccine. Twelve (44%) were confirmed microbiologically. G1 genotype was determined in six cases. According to the cohort study, vaccine efficacy for one dose was 34% (95%CI: -44 to 70), and was 67% (95%CI: 28 to 83) for two doses. Vaccine effectiveness was lower than expected. Early detection and isolation of cases have been instrumental in preventing new cases in schools. Copyright © 2014 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  5. Design and characterization of a fully differential MEMS accelerometer fabricated using MetalMUMPs technology.

    Science.gov (United States)

    Qu, Peng; Qu, Hongwei

    2013-05-02

    This paper presents a fully differential single-axis accelerometer fabricated using the MetalMUMPs process. The unique structural configuration and common-centriod wiring of the metal electrodes enables a fully differential sensing scheme with robust metal sensing structures. CoventorWare is used in structural and electrical design and simulation of the fully differential accelerometer. The MUMPs foundry fabrication process of the sensor allows for high yield, good process consistency and provides 20 μm structural thickness of the sensing element, which makes the capacitive sensing eligible. In device characterization, surface profile of the fabricated device is measured using a Veeco surface profilometer; and mean and gradient residual stress in the nickel structure are calculated as approximately 94.7 MPa and -5.27 MPa/μm, respectively. Dynamic characterization of the sensor is performed using a vibration shaker with a high-end commercial calibrating accelerometer as reference. The sensitivity of the sensor is measured as 0.52 mV/g prior to off-chip amplification. Temperature dependence of the sensing capacitance is also characterized. A -0.021fF/°C is observed. The findings in the presented work will provide useful information for design of sensors and actuators such as accelerometers, gyroscopes and electrothermal actuators that are to be fabricated using MetalMUMPs technology.

  6. Design and Characterization of a Fully Differential MEMS Accelerometer Fabricated Using MetalMUMPs Technology

    Directory of Open Access Journals (Sweden)

    Hongwei Qu

    2013-05-01

    Full Text Available This paper presents a fully differential single-axis accelerometer fabricated using the MetalMUMPs process. The unique structural configuration and common-centriod wiring of the metal electrodes enables a fully differential sensing scheme with robust metal sensing structures. CoventorWare is used in structural and electrical design and simulation of the fully differential accelerometer. The MUMPs foundry fabrication process of the sensor allows for high yield, good process consistency and provides 20 μm structural thickness of the sensing element, which makes the capacitive sensing eligible. In device characterization, surface profile of the fabricated device is measured using a Veeco surface profilometer; and mean and gradient residual stress in the nickel structure are calculated as approximately 94.7 MPa and −5.27 MPa/μm, respectively. Dynamic characterization of the sensor is performed using a vibration shaker with a high-end commercial calibrating accelerometer as reference. The sensitivity of the sensor is measured as 0.52 mV/g prior to off-chip amplification. Temperature dependence of the sensing capacitance is also characterized. A −0.021fF/°C is observed. The findings in the presented work will provide useful information for design of sensors and actuators such as accelerometers, gyroscopes and electrothermal actuators that are to be fabricated using MetalMUMPs technology.

  7. The potential dysfunction of otolith organs in patients after mumps infection.

    Science.gov (United States)

    Zhou, Yu-Juan; Yu, Jing; Wu, Yong-Zhen; Tian, Liang; Han, Zhao; Wang, Jing; Chi, Fang-Lu

    2017-01-01

    To investigate the relationship between mumps and the extent of hearing impairment and otolith organ damage. A total of 27 patients with unilateral hearing impairment following mumps were enrolled. The degrees of hearing loss and otolith organ damage were confirmed by audiometric and vestibular evoked myogenic potential [VEMP] tests. All the results were compared and analyzed using Stata 13.0 software for Windows. The VEMP thresholds of the affected ears were significantly higher than those of the unaffected ears in both tests (cervical VEMP [cVEMP] test and ocular VEMP [oVEMP] test; p = 0.000 and 0.001, respectively). The mean cVEMP and oVEMP threshold values of the affected ears with hearing impairment for ≤10 years were significantly lower than those of affected ears with hearing impairment for >10 years [p = 0.009 and 0.004, respectively]. Deafness resulting from mumps is usually profound and permanent, which indicates severe damage to the cochlea due to the disease. The functions of otolith organs in the vestibular system are also impaired. Over time, the function of the otolith organs or their neural pathway may suffer secondary damage.

  8. STATE OF MEASLES, RUBELLA AND MUMPS IN THE SARATOV REGION IN 2001—2013 YEARS

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    T. N. Buchkova

    2014-01-01

    Full Text Available The analysis of state reports «On the sanitary-epidemiological situation in Saratov region» for 2001—2013 years. In 2003 noted the maximum increase in the incidence of measles to 2.16 per 100 thousand population. Since 2007 by 2011 in the region of measles cases registered. However in 2012 in the Saratov region recorded four cases of measles adults (index — 0.15 per 100 thousand population and in 2013 — 52 cases of measles (index — 2.07 per 100 thousand population, of these, 17 cases-importations. In 2010 pronounced decrease was registered rubella (in 6389 times compared to 2001. In 2011 incidence of rubella is not registered. Incidence rates in 2012 and 2013 were, respectively, 0.2 and 0.04 per 100.000 populations. Since 2002, the incidence of mumps decreased 83-fold (from 6.65 in 2002 to 0,08 in 2012. In 2013 mumps incidence in the region is not registered. Analysis of the state vaccinated against measles, rubella and mumps shows that the region as a whole maintained a consistently high (not less than 95.0% immunization coverage of children and adults from 18 to 35 years.

  9. Focal attenuation of specific electroencephalographic power over the right parahippocampal region during transcerebral copper screening in living subjects and hemispheric asymmetric voltages in fixed brain tissue.

    Science.gov (United States)

    Rouleau, Nicolas; Lehman, Brendan; Persinger, Michael A

    2016-08-01

    Covering the heads of human volunteers with a toque lined with copper mesh compared to no mesh resulted in significant diminishments in quantitative electroencephalographic power within theta and beta-gamma bands over the right caudal hemisphere. The effect was most evident in women compared to men. The significant attenuation of power was verified by LORETA (low resolution electromagnetic tomography) within the parahippocampal region of the right hemisphere. Direct measurements of frequency-dependent voltages of coronal section preserved in ethanol-formalin-acetic acid from our human brain collection revealed consistently elevated power (0.2μV(2)Hz(-1)) in right hemispheric structures compared to left. The discrepancy was most pronounced in the grey (cortical) matter of the right parahippocampal region. Probing the superficial convexities of the cerebrum in an unsectioned human brain demonstrated rostrocaudal differences in hemispheric spectral power density asymmetries, particularly over caudal and parahippocampal regions, which were altered as a function of the chemical and spatial contexts imposed upon the tissue. These results indicate that the heterogeneous response of the human cerebrum to covering of the head by a thin conductor could reflect an intrinsic structure and unique electrical property of the (entorhinal) cortices of the right caudal hemisphere that persists in fixed tissue.

  10. Influenza Vaccine, Live Intranasal

    Science.gov (United States)

    ... the recombinant influenza vaccine (RIV). The nasal spray flu vaccine (live attenuated influenza vaccine or LAIV) should NOT ... to your doctor or pharmacist about the best flu vaccine option for you or your family.

  11. A live attenuated BCG vaccine overexpressing multistage antigens Ag85B and HspX provides superior protection against Mycobacterium tuberculosis infection.

    Science.gov (United States)

    Yuan, Xuefeng; Teng, Xindong; Jing, Yukai; Ma, Jilei; Tian, Maopeng; Yu, Qi; Zhou, Lei; Wang, Ruibo; Wang, Weihua; Li, Li; Fan, Xionglin

    2015-12-01

    Tuberculosis (TB) remains one of the most menacing infectious diseases, although attenuated Mycobacterium bovis Bacillus Calmette-Guerin (BCG) vaccine has been widely used to protect children against primary TB. There are increasing evidences that rapid growing and dormant Mycobacterium tuberculosis (M. tuberculosis) coexist in vivo after infection. However, BCG vaccine only elicits cell-mediated immune responses to secretory antigens expressed by rapid growing pathogen. BCG vaccine is thus unable to thwart the reactivation of latent tuberculosis infection (LTBI), and its protection wanes over age after neonatal immunization. In order to extend its ability for a durable protection, a novel recombinant BCG (rBCG) strain, named rBCG::XB, was constructed by overexpressing immunodominant multistage antigens of Ag85B and HspX, which are expressed by both rapid replicating and dormant M. tuberculosis. Long-term protective effect and immunogenicity of rBCG::XB were compared with the parental BCG in vaccinated C57BL/6 mice. Our results demonstrated that rBCG::XB provided the stronger and long-lasting protection against M. tuberculosis H37Rv intranasal infection than BCG. The rBCG::XB not only elicited the more durable multistage antigen-specific CD4(+)Th1-biased immune responses and specific polyfunctional CD4(+)T cells but also augmented the CD8(+) CTL effects against Ag85B in vivo. In particular, higher levels of CD4(+) TEM and CD8(+) TCM cells, dominated by IL2(+) CD4(+) and CD8(+) TCM cells, were obtained in the spleen of rBCG::XB vaccinated mice. Therefore, our findings indicate that rBCG::XB is a promising candidate to improve the efficacy of BCG.

  12. Safety and immunogenicity of an oral DNA vaccine encoding Sip of Streptococcus agalactiae from Nile tilapia Oreochromis niloticus delivered by live attenuated Salmonella typhimurium.

    Science.gov (United States)

    Huang, L Y; Wang, K Y; Xiao, D; Chen, D F; Geng, Y; Wang, J; He, Y; Wang, E L; Huang, J L; Xiao, G Y

    2014-05-01

    Attenuated Salmonella typhimurium SL7207 was used as a carrier for a reconstructed DNA vaccine against Streptococcus agalactiae. A 1.02 kb DNA fragment, encoding for a portion of the surface immunogenic protein (Sip) of S. agalactiae was inserted into pVAX1. The recombinant plasmid pVAX1-sip was transfected in EPC cells to detect the transient expression by an indirect immunofluorescence assay, together with Western blot analysis. The pVAX1-sip was transformed by electroporation into SL7207. The stability of pVAX1-sip into Salmonella was over 90% after 50 generations with antibiotic selection in vitro while remained stable over 80% during 35 generations under antibiotic-free conditions. The LD50 of SL/pVAX1-sip was 1.7 × 10(11) CFU/fish by intragastric administration which indicated a quite low virulence. Tilapias were inoculated orally at 10(8) CFU/fish, the recombinant bacteria were found present in intestinal tract, spleens and livers and eventually eliminated from the tissues 4 weeks after immunization. Fish immunized at 10(7), 10(8) and 10(9) CFU/fish with different immunization times caused various levels of serum antibody and an effective protection against lethal challenge with the wild-type strain S. agalactiae. Integration studies showed that the pVAX1-sip did not integrate with tilapia chromosomes. The DNA vaccine SL/pVAX1-sip was proved to be safe and effective in protecting tilapias against S. agalactiae infection.

  13. Ribosomal Initiation Complex Assembly within the Wild-Strain of Coxsackievirus B3 and Live-Attenuated Sabin3-like IRESes during the Initiation of Translation

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    Nathalie Chamond

    2013-02-01

    Full Text Available Coxsackievirus B3 (CVB3 is an enterovirus of the family of Picornaviridae. The Group B coxsackieviruses include six serotypes (B1 to B6 that cause a variety of human diseases, including myocarditis, meningitis, and diabetes. Among the group B, the B3 strain is mostly studied for its cardiovirulence and its ability to cause acute and persistent infections. Translation initiation of CVB3 RNA has been shown to be mediated by a highly ordered structure of the 5’-untranslated region (5’UTR, which harbors an internal ribosome entry site (IRES. Translation initiation is a complex process in which initiator tRNA, 40S and 60S ribosomal subunits are assembled by eukaryotic initiation factors (eIFs into an 80S ribosome at the initiation codon of the mRNA. We have previously addressed the question of whether the attenuating mutations of domain V of the poliovirus IRES were specific for a given genomic context or whether they could be transposed and extrapolated to a genomic related virus, i.e., CVB3 wild-type strain. In this context, we have described that Sabin3-like mutation (U473→C introduced in CVB3 genome led to a defective mutant with a serious reduction in translation efficiency. In this study, we analyzed the efficiency of formation of ribosomal initiation complexes 48S and 80S through 10%–30% and 10%–50% sucrose gradients using rabbit reticulocyte lysates (RRLs and stage-specific translation inhibitors: 5'-Guanylyl-imidodiphosphate (GMP-PNP and Cycloheximide (CHX, respectively. We demonstrated that the interaction of 48S and 80S ribosomal complexes within the mutant CVB3 RNA was abolished compared with the wild-type RNA by ribosome assembly analysis. Taken together, it is possible that the mutant RNA was unable to interact with some trans-acting factors critical for enhanced IRES function.

  14. A live attenuated recombinant dengue-4 virus vaccine candidate with restricted capacity for dissemination in mosquitoes and lack of transmission from vaccinees to mosquitoes.

    Science.gov (United States)

    Troyer, J M; Hanley, K A; Whitehead, S S; Strickman, D; Karron, R A; Durbin, A P; Murphy, B R

    2001-11-01

    2Adelta30 is a live dengue-4 virus vaccine candidate with a 30-nucleotide deletion in its 3'-untranslated region. To assess the transmissibility of 2Adelta30 by mosquitoes, we compared its in vivo replication in mosquitoes with that of its wild type DEN-4 parent. Both the vaccine candidate and wild type virus were equally able to infect the mosquito Toxorhynchites splendens after intrathoracic inoculation. Relative to its wild type parent, 2Adelta30 was slightly restricted in its ability to infect the midgut of Aedes aegypti mosquitoes fed on an artificial blood meal and was even more restricted in its ability to disseminate from the midgut to the salivary glands. Thus, the 30-nucleotide deletion rendered the vaccine candidate more sensitive than its wild type parent to the mosquito midgut escape barrier. Most significantly, 2Adelta30 was not transmitted to 352 Ae. albopictus mosquitoes fed on 10 vaccinees, all of whom were infected with the vaccine candidate.

  15. Detection of measles, mumps and rubella viruses by immuno-colorimetric assay and its application in focus reduction neutralization tests.

    Science.gov (United States)

    Vaidya, Sunil R; Kumbhar, Neelakshi S; Bhide, Vandana S

    2014-12-01

    Measles, mumps and rubella are vaccine-preventable diseases; however limited epidemiological data are available from low-income or developing countries. Thus, it is important to investigate the transmission of these viruses in different geographical regions. In this context, a cell culture-based rapid and reliable immuno-colorimetric assay (ICA) was established and its utility studied. Twenty-three measles, six mumps and six rubella virus isolates and three vaccine strains were studied. Detection by ICA was compared with plaque and RT-PCR assays. In addition, ICA was used to detect viruses in throat swabs (n = 24) collected from patients with suspected measles or mumps. Similarly, ICA was used in a focus reduction neutralization test (FRNT) and the results compared with those obtained by a commercial IgG enzyme immuno assay. Measles and mumps virus were detected 2 days post-infection in Vero or Vero-human signaling lymphocytic activation molecule cells, whereas rubella virus was detected 3 days post-infection in Vero cells. The blue stained viral foci were visible by the naked eye or through a magnifying glass. In conclusion, ICA was successfully used on 35 virus isolates, three vaccine strains and clinical specimens collected from suspected cases of measles and mumps. Furthermore, an application of ICA in a neutralization test (i.e., FRNT) was documented; this may be useful for sero-epidemiological, cross-neutralization and pre/post-vaccine studies. © 2014 The Societies and Wiley Publishing Asia Pty Ltd.

  16. Acetaminophen (paracetamol) use, measles-mumps-rubella vaccination, and autistic disorder: the results of a parent survey.

    Science.gov (United States)

    Schultz, Stephen T; Klonoff-Cohen, Hillary S; Wingard, Deborah L; Akshoomoff, Natacha A; Macera, Caroline A; Ji, Ming

    2008-05-01

    The present study was performed to determine whether acetaminophen (paracetamol) use after the measles-mumps-rubella vaccination could be associated with autistic disorder. This case-control study used the results of an online parental survey conducted from 16 July 2005 to 30 January 2006, consisting of 83 children with autistic disorder and 80 control children. Acetaminophen use after measles-mumps-rubella vaccination was significantly associated with autistic disorder when considering children 5 years of age or less (OR 6.11, 95% CI 1.42-26.3), after limiting cases to children with regression in development (OR 3.97, 95% CI 1.11-14.3), and when considering only children who had post-vaccination sequelae (OR 8.23, 95% CI 1.56-43.3), adjusting for age, gender, mother's ethnicity, and the presence of illness concurrent with measles-mumps-rubella vaccination. Ibuprofen use after measles-mumps-rubella vaccination was not associated with autistic disorder. This preliminary study found that acetaminophen use after measles-mumps-rubella vaccination was associated with autistic disorder.

  17. Increased levels of cytokines in cerebrospinal fluid of children with aseptic meningitis caused by mumps virus and echovirus 30.

    Science.gov (United States)

    Sulik, A; Kroten, A; Wojtkowska, M; Oldak, E

    2014-01-01

    We measured levels of pro-inflammatory cytokines in the cerebrospinal fluid (CSF) of patients with mumps meningitis, enteroviral echovirus 30 meningitis and children without central nervous system infection to investigate whether these molecules were involved in the pathogenesis of viral meningitis. The CSF was obtained from 62 children suspected with meningitis. These patients were classified to the mumps meningitis (n = 19), echovirus 30 meningitis (n = 22) and non-meningitis (n = 21) groups. The concentrations of interleukin-1 (IL-1), interleukin-1 soluble receptor type 2 (IL-1R2), interleukin-8 (IL-8), human interferon gamma (IFN-γ) and human tumour necrosis factor alpha (TNF-α) were determined by immunoassay. A significant increase was noted in the levels of IL-8, TNF-α and IL-1R2 in the CSF of both meningitis groups as compared to controls. The concentrations of IFN-γ and IL-1 differed significantly only between the mumps group and control. The levels of IL-1, IFN-γ and TNF-α were significantly higher in mumps meningitis when compared to the echovirus 30 group. Of all cytokines examined, only IFN-γ correlated with pleocytosis (r = 0.58) in the mumps meningitis group. The increased CSF cytokine levels are markers of meningeal inflammation, and each virus may cause a specific profile of the cytokine pattern.

  18. Evaluation of anti-measles and anti-mumps vaccination coverage in a cohort of youth in South-Centre of Sicily, Italy

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    Claudia Lo Magno

    2015-12-01

    Full Text Available This study examined a cohort of young people from South Centre Sicily, Italy, in order to evaluate anti-measles anti-mumps vaccination coverage. It is shown that, in proportion, an antibody protection against mumps is greater than an antibody protection against measles and also it causes acute episodes in some subjects vaccinated.

  19. 一所山区学校流行性腮腺炎暴发调查和应急接种效果评价%Investigation on a Mumps Outbreak and Evaluation on Emergent Vaccination Effect at a School of a Mountain Village

    Institute of Scientific and Technical Information of China (English)

    徐福根; 童卫星; 闻洪根; 陈月光; 陈康凯; 李安乐; 许向军

    2001-01-01

    [目的]调查疫情,控制暴发,评价应急接种效果.[方法]开展暴发调查,核实诊断;对全校无流行性腮腺炎(流腮)病史的学生应急接种流腮疫苗,并测定抗体效价.[结果]疫情持续约4个月,罹患率全校学生为27.47%,寄宿生高于走读生(P<0.01);检测病人23例,抗体滴度≥1:64的占65.22%;应急接种后,接种者的抗体阳转率和GMRT分别为48.57%(17/35)和2.8,抗体滴度≥1:64者占11.76%;应急接种后17d暴发终止.[结论]这是一起由于传染源输入、延误防制措施、居住拥挤和密切接触引起的山区学校流腮暴发,应急接种流腮疫苗有较好的效果.%[Objective]To survey epidemic situation,control outbreak and evaluate emergent vaccination effect. [Methods]Outbreak survey and verified diagnosis were carried out. All students without mumps history were emergently inoculated with mumps vaccine. Mumps antibody was measured by haemagglutination inhibition test. [Results]Epidemic situation lasted about four months. The attack rate of mumps in all students was 27.47%. The rate in the resident students was significantly higher than that in the non-resident students(P<0.01). Sera from 23 patients were detected. The percentage of HI antibody titers≥1:64 was 65.22%. HI antibody positive seroconversion rate and GMRT of the vaccinees after emergent vaccination were 48.57% (17/35) and 2.8 respectively. Proportion of HI antibody titer ≥1:64 accounted for 11.76%. The outbreak was stopped within 17 days after emergent immunization. [Conclusions]This mumps outbreak at a school of a mountain village is due to import of infection source,delay of control measure, crowded living condition and close contact. The emergent vaccination with mumps vaccine is efficient.

  20. Evaluation of live attenuated H7N3 and H7N7 vaccine viruses for their receptor binding preferences, immunogenicity in ferrets and cross reactivity to the novel H7N9 virus.

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    Qi Xu

    Full Text Available Live attenuated influenza vaccine (LAIV candidates of the H7 subtype, A/Netherlands/219/03 (H7N7, NL03 ca and A/chicken/British Columbia/CN-6/2004 (H7N3, BC04 ca, were evaluated for their receptor binding specificity and immunogenicity in ferrets. The BC04 ca virus exhibited α2,3-SA and α2,6-SA dual receptor binding preference while the NL03 ca virus preferentially bound to α2,3-SA. Substitution of the Q226 and G228 (Q-G by the L226 and S228 (L-S residues in the HA improved binding to α2,6-SA for NL03 ca. The vaccine viruses with L-S retained the attenuation phenotype. NL03 L-S ca replicated more efficiently than the original NL03 ca virus in the upper respiratory tract of ferrets, and induced higher levels of humoral and cellular immune responses. Prior vaccination with seasonal LAIV reduced H7-specific antibody responses, but did not reduce the H7N7 vaccine mediated protection against a heterologous H7N3 BC04 wt virus infection in ferrets. In addition, the H7N3 and H7N7 vaccine immunized ferret sera cross reacted with the newly emerged H7N9 virus. These data, in combination with the safety data from previously conducted Phase 1 studies, suggest that these vaccines may have a role in responding to the threat posed by the H7N9 virus.

  1. A molecularly cloned, live-attenuated japanese encephalitis vaccine SA14-14-2 virus: a conserved single amino acid in the ij Hairpin of the Viral E glycoprotein determines neurovirulence in mice.

    Science.gov (United States)

    Yun, Sang-Im; Song, Byung-Hak; Kim, Jin-Kyoung; Yun, Gil-Nam; Lee, Eun-Young; Li, Long; Kuhn, Richard J; Rossmann, Michael G; Morrey, John D; Lee, Young-Min

    2014-07-01

    Japanese encephalitis virus (JEV), a mosquito-borne flavivirus that causes fatal neurological disease in humans, is one of the most important emerging pathogens of public health significance. JEV represents the JE serogroup, which also includes West Nile, Murray Valley encephalitis, and St. Louis encephalitis viruses. Within this serogroup, JEV is a vaccine-preventable pathogen, but the molecular basis of its neurovirulence remains unknown. Here, we constructed an infectious cDNA of the most widely used live-attenuated JE vaccine, SA14-14-2, and rescued from the cDNA a molecularly cloned virus, SA14-14-2MCV, which displayed in vitro growth properties and in vivo attenuation phenotypes identical to those of its parent, SA14-14-2. To elucidate the molecular mechanism of neurovirulence, we selected three independent, highly neurovirulent variants (LD50, 1.5×105 PFU) by serial intracerebral passage in mice. Complete genome sequence comparison revealed a total of eight point mutations, with a common single G1708→A substitution replacing a Gly with Glu at position 244 of the viral E glycoprotein. Using our infectious SA14-14-2 cDNA technology, we showed that this single Gly-to-Glu change at E-244 is sufficient to confer lethal neurovirulence in mice, including rapid development of viral spread and tissue inflammation in the central nervous system. Comprehensive site-directed mutagenesis of E-244, coupled with homology-based structure modeling, demonstrated a novel essential regulatory role in JEV neurovirulence for E-244, within the ij hairpin of the E dimerization domain. In both mouse and human neuronal cells, we further showed that the E-244 mutation altered JEV infectivity in vitro, in direct correlation with the level of neurovirulence in vivo, but had no significant impact on viral RNA replication. Our results provide a crucial step toward developing novel therapeutic and preventive strategies against JEV and possibly other encephalitic flaviviruses.

  2. Implication of respiratory syncytial virus (RSV) F transgene sequence heterogeneity observed in Phase 1 evaluation of MEDI-534, a live attenuated parainfluenza type 3 vectored RSV vaccine.

    Science.gov (United States)

    Yang, Chin-Fen; Wang, C Kathy; Malkin, Elissa; Schickli, Jeanne H; Shambaugh, Cindy; Zuo, Fengrong; Galinski, Mark S; Dubovsky, Filip; Tang, Roderick S

    2013-06-10

    MEDI-534 is the first live vectored RSV vaccine candidate to be evaluated in seronegative children. It consists of the bovine parainfluenza virus type 3 (PIV3) genome with substituted human PIV3 F and HN glycoproteins engineered to express RSV F protein. A Phase 1 study of 49 healthy RSV and PIV3 seronegative children 6 to <24 months of age demonstrated an acceptable safety profile at the following doses: 10(4), 10(5) and 10(6)TCID50. After 3 doses of MEDI-534 at 10(6)TCID50, administered at 0, 2 and 4 month intervals, 100% of subjects seroresponded to PIV3, whereas only 50% seroresponded to RSV. To investigate the discordance in seroresponse rates, the RSV F transgene and its flanking non-coding nucleotides were sequenced from shed virus recovered from the nasal washes of 24 MEDI-534-vaccinated children. Eleven out of 24 samples contained no nucleotide changes in the analyzed region. The other 13 samples contained mixtures of variant subpopulations. Fifty-five percent exhibited changes in the transcription termination poly A gene sequences of the upstream bPIV3N gene while 21% had variant subpopulations in the RSV F open reading frame that resulted in pre-mature stop codons. Both types of changes are expected to reduce RSV F expression. Evaluation of the administered vaccine by dual immunofluorescence staining showed ~2.5% variants with low or no RSV F expression while single nucleotide primer extension detected ~1% variation at nucleotide 2045 that resulted in a pre-mature translational termination at codon 85. An association between shedding of variants and lower RSV F serological response was observed but it was not possible to establish a definitive clinical significance due to the small number of subjects in this study.

  3. Search for the lepton-flavor violating decays $B^0_s \\rightarrow e^{\\pm}\\mu^{\\mp}$ and $B^0 \\rightarrow e^{\\pm} \\mu^{\\mp}$

    CERN Document Server

    Aaij, R.; Adinolfi, M.; Adrover, C.; Affolder, A.; Ajaltouni, Z.; Albrecht, J.; Alessio, F.; Alexander, M.; Ali, S.; Alkhazov, G.; Alvarez Cartelle, P.; Alves Jr, A.A.; Amato, S.; Amerio, S.; Amhis, Y.; Anderlini, L.; Anderson, J.; Andreassen, R.; Andrews, J.E.; Appleby, R.B.; Aquines Gutierrez, O.; Archilli, F.; Artamonov, A.; Artuso, M.; Aslanides, E.; Auriemma, G.; Baalouch, M.; Bachmann, S.; Back, J.J.; Baesso, C.; Balagura, V.; Baldini, W.; Barlow, R.J.; Barschel, C.; Barsuk, S.; Barter, W.; Bauer, Th.; Bay, A.; Beddow, J.; Bedeschi, F.; Bediaga, I.; Belogurov, S.; Belous, K.; Belyaev, I.; Ben-Haim, E.; Bencivenni, G.; Benson, S.; Benton, J.; Berezhnoy, A.; Bernet, R.; Bettler, M.-O.; van Beuzekom, M.; Bien, A.; Bifani, S.; Bird, T.; Bizzeti, A.; Bjørnstad, P.M.; Blake, T.; Blanc, F.; Blouw, J.; Blusk, S.; Bocci, V.; Bondar, A.; Bondar, N.; Bonivento, W.; Borghi, S.; Borgia, A.; Bowcock, T.J.V.; Bowen, E.; Bozzi, C.; Brambach, T.; van den Brand, J.; Bressieux, J.; Brett, D.; Britsch, M.; Britton, T.; Brook, N.H.; Brown, H.; Burducea, I.; Bursche, A.; Busetto, G.; Buytaert, J.; Cadeddu, S.; Callot, O.; Calvi, M.; Calvo Gomez, M.; Camboni, A.; Campana, P.; Campora Perez, D.; Carbone, A.; Carboni, G.; Cardinale, R.; Cardini, A.; Carranza-Mejia, H.; Carson, L.; Carvalho Akiba, K.; Casse, G.; Castillo Garcia, L.; Cattaneo, M.; Cauet, Ch.; Cenci, R.; Charles, M.; Charpentier, Ph.; Chen, P.; Chiapolini, N.; Chrzaszcz, M.; Ciba, K.; Cid Vidal, X.; Ciezarek, G.; Clarke, P.E.L.; Clemencic, M.; Cliff, H.V.; Closier, J.; Coca, C.; Coco, V.; Cogan, J.; Cogneras, E.; Collins, P.; Comerma-Montells, A.; Contu, A.; Cook, A.; Coombes, M.; Coquereau, S.; Corti, G.; Couturier, B.; Cowan, G.A.; Craik, D.C.; Cunliffe, S.; Currie, R.; D'Ambrosio, C.; David, P.; David, P.N.Y.; Davis, A.; De Bonis, I.; De Bruyn, K.; De Capua, S.; De Cian, M.; De Miranda, J.M.; De Paula, L.; De Silva, W.; De Simone, P.; Decamp, D.; Deckenhoff, M.; Del Buono, L.; Déléage, N.; Derkach, D.; Deschamps, O.; Dettori, F.; Di Canto, A.; Dijkstra, H.; Dogaru, M.; Donleavy, S.; Dordei, F.; Dosil Suárez, A.; Dossett, D.; Dovbnya, A.; Dupertuis, F.; Durante, P.; Dzhelyadin, R.; Dziurda, A.; Dzyuba, A.; Easo, S.; Egede, U.; Egorychev, V.; Eidelman, S.; van Eijk, D.; Eisenhardt, S.; Eitschberger, U.; Ekelhof, R.; Eklund, L.; El Rifai, I.; Elsasser, Ch.; Falabella, A.; Färber, C.; Fardell, G.; Farinelli, C.; Farry, S.; Fave, V.; Ferguson, D.; Fernandez Albor, V.; Ferreira Rodrigues, F.; Ferro-Luzzi, M.; Filippov, S.; Fiore, M.; Fitzpatrick, C.; Fontana, M.; Fontanelli, F.; Forty, R.; Francisco, O.; Frank, M.; Frei, C.; Frosini, M.; Furcas, S.; Furfaro, E.; Gallas Torreira, A.; Galli, D.; Gandelman, M.; Gandini, P.; Gao, Y.; Garofoli, J.; Garosi, P.; Garra Tico, J.; Garrido, L.; Gaspar, C.; Gauld, R.; Gersabeck, E.; Gersabeck, M.; Gershon, T.; Ghez, Ph.; Gibson, V.; Giubega, L.; Gligorov, V.V.; Göbel, C.; Golubkov, D.; Golutvin, A.; Gomes, A.; Gordon, H.; Grabalosa Gándara, M.; Graciani Diaz, R.; Granado Cardoso, L.A.; Graugés, E.; Graziani, G.; Grecu, A.; Greening, E.; Gregson, S.; Griffith, P.; Grünberg, O.; Gui, B.; Gushchin, E.; Guz, Yu.; Gys, T.; Hadjivasiliou, C.; Haefeli, G.; Haen, C.; Haines, S.C.; Hall, S.; Hamilton, B.; Hampson, T.; Hansmann-Menzemer, S.; Harnew, N.; Harnew, S.T.; Harrison, J.; Hartmann, T.; He, J.; Head, T.; Heijne, V.; Hennessy, K.; Henrard, P.; Hernando Morata, J.A.; van Herwijnen, E.; Hicheur, A.; Hicks, E.; Hill, D.; Hoballah, M.; Hombach, C.; Hopchev, P.; Hulsbergen, W.; Hunt, P.; Huse, T.; Hussain, N.; Hutchcroft, D.; Hynds, D.; Iakovenko, V.; Idzik, M.; Ilten, P.; Jacobsson, R.; Jaeger, A.; Jans, E.; Jaton, P.; Jawahery, A.; Jing, F.; John, M.; Johnson, D.; Jones, C.R.; Joram, C.; Jost, B.; Kaballo, M.; Kandybei, S.; Kanso, W.; Karacson, M.; Karbach, T.M.; Kenyon, I.R.; Ketel, T.; Keune, A.; Khanji, B.; Kochebina, O.; Komarov, I.; Koopman, R.F.; Koppenburg, P.; Korolev, M.; Kozlinskiy, A.; Kravchuk, L.; Kreplin, K.; Kreps, M.; Krocker, G.; Krokovny, P.; Kruse, F.; Kucharczyk, M.; Kudryavtsev, V.; Kvaratskheliya, T.; La Thi, V.N.; Lacarrere, D.; Lafferty, G.; Lai, A.; Lambert, D.; Lambert, R.W.; Lanciotti, E.; Lanfranchi, G.; Langenbruch, C.; Latham, T.; Lazzeroni, C.; Le Gac, R.; van Leerdam, J.; Lees, J.-P.; Lefèvre, R.; Leflat, A.; Lefrançois, J.; Leo, S.; Leroy, O.; Lesiak, T.; Leverington, B.; Li, Y.; Li Gioi, L.; Liles, M.; Lindner, R.; Linn, C.; Liu, B.; Liu, G.; Lohn, S.; Longstaff, I.; Lopes, J.H.; Lopez-March, N.; Lu, H.; Lucchesi, D.; Luisier, J.; Luo, H.; Machefert, F.; Machikhiliyan, I.V.; Maciuc, F.; Maev, O.; Malde, S.; Manca, G.; Mancinelli, G.; Maratas, J.; Marconi, U.; Marino, P.; Märki, R.; Marks, J.; Martellotti, G.; Martens, A.; Martín Sánchez, A.; Martinelli, M.; Martinez Santos, D.; Martins Tostes, D.; Massafferri, A.; Matev, R.; Mathe, Z.; Matteuzzi, C.; Maurice, E.; Mazurov, A.; Mc Skelly, B.; McCarthy, J.; McNab, A.; McNulty, R.; Meadows, B.; Meier, F.; Meissner, M.; Merk, M.; Milanes, D.A.; Minard, M.-N.; Molina Rodriguez, J.; Monteil, S.; Moran, D.; Morawski, P.; Mordà, A.; Morello, M.J.; Mountain, R.; Mous, I.; Muheim, F.; Müller, K.; Muresan, R.; Muryn, B.; Muster, B.; Naik, P.; Nakada, T.; Nandakumar, R.; Nasteva, I.; Needham, M.; Neubert, S.; Neufeld, N.; Nguyen, A.D.; Nguyen, T.D.; Nguyen-Mau, C.; Nicol, M.; Niess, V.; Niet, R.; Nikitin, N.; Nikodem, T.; Nomerotski, A.; Novoselov, A.; Oblakowska-Mucha, A.; Obraztsov, V.; Oggero, S.; Ogilvy, S.; Okhrimenko, O.; Oldeman, R.; Orlandea, M.; Otalora Goicochea, J.M.; Owen, P.; Oyanguren, A.; Pal, B.K.; Palano, A.; Palutan, M.; Panman, J.; Papanestis, A.; Pappagallo, M.; Parkes, C.; Parkinson, C.J.; Passaleva, G.; Patel, G.D.; Patel, M.; Patrick, G.N.; Patrignani, C.; Pavel-Nicorescu, C.; Pazos Alvarez, A.; Pellegrino, A.; Penso, G.; Pepe Altarelli, M.; Perazzini, S.; Perez Trigo, E.; Pérez-Calero Yzquierdo, A.; Perret, P.; Perrin-Terrin, M.; Pescatore, L.; Pessina, G.; Petridis, K.; Petrolini, A.; Phan, A.; Picatoste Olloqui, E.; Pietrzyk, B.; Pilař, T.; Pinci, D.; Playfer, S.; Plo Casasus, M.; Polci, F.; Polok, G.; Poluektov, A.; Polycarpo, E.; Popov, A.; Popov, D.; Popovici, B.; Potterat, C.; Powell, A.; Prisciandaro, J.; Pritchard, A.; Prouve, C.; Pugatch, V.; Puig Navarro, A.; Punzi, G.; Qian, W.; Rademacker, J.H.; Rakotomiaramanana, B.; Rangel, M.S.; Raniuk, I.; Rauschmayr, N.; Raven, G.; Redford, S.; Reid, M.M.; dos Reis, A.C.; Ricciardi, S.; Richards, A.; Rinnert, K.; Rives Molina, V.; Roa Romero, D.A.; Robbe, P.; Roberts, D.A.; Rodrigues, E.; Rodriguez Perez, P.; Roiser, S.; Romanovsky, V.; Romero Vidal, A.; Rouvinet, J.; Ruf, T.; Ruffini, F.; Ruiz, H.; Ruiz Valls, P.; Sabatino, G.; Saborido Silva, J.J.; Sagidova, N.; Sail, P.; Saitta, B.; Salustino Guimaraes, V.; Salzmann, C.; Sanmartin Sedes, B.; Sannino, M.; Santacesaria, R.; Santamarina Rios, C.; Santovetti, E.; Sapunov, M.; Sarti, A.; Satriano, C.; Satta, A.; Savrie, M.; Savrina, D.; Schaack, P.; Schiller, M.; Schindler, H.; Schlupp, M.; Schmelling, M.; Schmidt, B.; Schneider, O.; Schopper, A.; Schune, M.-H.; Schwemmer, R.; Sciascia, B.; Sciubba, A.; Seco, M.; Semennikov, A.; Senderowska, K.; Sepp, I.; Serra, N.; Serrano, J.; Seyfert, P.; Shapkin, M.; Shapoval, I.; Shatalov, P.; Shcheglov, Y.; Shears, T.; Shekhtman, L.; Shevchenko, O.; Shevchenko, V.; Shires, A.; Silva Coutinho, R.; Sirendi, M.; Skwarnicki, T.; Smith, N.A.; Smith, E.; Smith, J.; Smith, M.; Sokoloff, M.D.; Soler, F.J.P.; Soomro, F.; Souza, D.; Souza De Paula, B.; Spaan, B.; Sparkes, A.; Spradlin, P.; Stagni, F.; Stahl, S.; Steinkamp, O.; Stevenson, S.; Stoica, S.; Stone, S.; Storaci, B.; Straticiuc, M.; Straumann, U.; Subbiah, V.K.; Sun, L.; Swientek, S.; Syropoulos, V.; Szczekowski, M.; Szczypka, P.; Szumlak, T.; T'Jampens, S.; Teklishyn, M.; Teodorescu, E.; Teubert, F.; Thomas, C.; Thomas, E.; van Tilburg, J.; Tisserand, V.; Tobin, M.; Tolk, S.; Tonelli, D.; Topp-Joergensen, S.; Torr, N.; Tournefier, E.; Tourneur, S.; Tran, M.T.; Tresch, M.; Tsaregorodtsev, A.; Tsopelas, P.; Tuning, N.; Ubeda Garcia, M.; Ukleja, A.; Urner, D.; Ustyuzhanin, A.; Uwer, U.; Vagnoni, V.; Valenti, G.; Vallier, A.; Van Dijk, M.; Vazquez Gomez, R.; Vazquez Regueiro, P.; Vázquez Sierra, C.; Vecchi, S.; Velthuis, J.J.; Veltri, M.; Veneziano, G.; Vesterinen, M.; Viaud, B.; Vieira, D.; Vilasis-Cardona, X.; Vollhardt, A.; Volyanskyy, D.; Voong, D.; Vorobyev, A.; Vorobyev, V.; Voß, C.; Voss, H.; Waldi, R.; Wallace, C.; Wallace, R.; Wandernoth, S.; Wang, J.; Ward, D.R.; Watson, N.K.; Webber, A.D.; Websdale, D.; Whitehead, M.; Wicht, J.; Wiechczynski, J.; Wiedner, D.; Wiggers, L.; Wilkinson, G.; Williams, M.P.; Williams, M.; Wilson, F.F.; Wimberley, J.; Wishahi, J.; Witek, M.; Wotton, S.A.; Wright, S.; Wu, S.; Wyllie, K.; Xie, Y.; Xing, Z.; Yang, Z.; Young, R.; Yuan, X.; Yushchenko, O.; Zangoli, M.; Zavertyaev, M.; Zhang, F.; Zhang, L.; Zhang, W.C.; Zhang, Y.; Zhelezov, A.; Zhokhov, A.; Zhong, L.; Zvyagin, A.

    2013-01-01

    A search for the lepton-flavour violating decays $B^0_s \\rightarrow e^{\\pm}\\mu^{\\mp}$ and $B^0 \\rightarrow e^{\\pm} \\mu^{\\mp}$ is performed with a data sample, corresponding to an integrated luminosity of 1.0 fb$^{-1}$ of $pp$ collisions at $\\sqrt{s} = 7$, TeV, collected by the LHCb experiment. The observed number of $B^0_s \\to e^{\\pm} \\mu^{\\mp}$ and $B^0 \\to e^{\\pm} \\mu^{\\mp}$ candidates is consistent with background expectations. Upper limits on the branching fractions of both decays are determined to be $BR(B^0_s \\to e^{\\pm} \\mu^{\\mp} 107$ TeV/c$^2$ and $M_{\\rm LQ} (B^0 \\to e^{\\pm} \\mu^{\\mp}) > 126$ TeV/c$^2$ at 95% C.L., and are a factor of two higher than the previous bounds.

  4. Unilateral Optic Neuritis: A Rare Complication after Measles-Mumps-Rubella Vaccination in a 30-Year-Old Woman

    Directory of Open Access Journals (Sweden)

    Chiara De Giacinto

    2016-01-01

    Full Text Available Purpose. To report a case of unilateral optic neuritis following Measles-Mumps-Rubella (MMR vaccination. Methods. A 30-year-old female developed unilateral optic neuritis five days after a Measles-Mumps-Rubella (MMR booster vaccination. The patient displayed unilateral involvement, with severe visual loss. However, visual acuity improved significantly after four days of intravenous steroid therapy with 500 mg/day of methylprednisolone. Conclusions. Optic neuritis is one of the rare complications associated with the mumps, measles, and rubella vaccine. It may be a toxic reaction to the nonviral component of the vaccine, but the exact etiology is unknown. Postvaccination neuritis is generally bilateral and usually affects children. In adults, unilateral optic neuritis is usually correlated with multiple sclerosis (MS.

  5. Healthcare workers and measles-mumps-rubella (MMR) status: how worried should we be about further outbreaks?

    Science.gov (United States)

    Basu, S; Giri, P; Adisesh, A; McNAUGHT, R

    2014-08-01

    Recently, a number of outbreaks of measles and mumps have occurred within the UK and Europe. Healthcare workers (HCWs) are at risk of contracting and transmitting disease to patients and staff. To examine this risk at the point of entry to healthcare, we assessed the serological results of new HCWs presenting for pre-placement clearance without evidence of measles-mumps-rubella (MMR) immunity between 1 April 2010 and 31 March 2012. Overall rates of serological positivity to MMR across all age groups were 88·2%, 68·8% and 93·9%, respectively. With regard to measles and mumps, there were statistically significant decreases in the percentage of HCWs born after 1980 that had positive serology (P outbreak within this cohort of HCWs appears low.

  6. 脊髓灰质炎减毒活疫苗强化免疫评价指标体系的构建%ESTABLISHMENT OF THE INDEX SYSTEM ON ASSESSMENT OF ORAL POLIOMYELITIS ATTENUATED LIVE VACCINE MASS CAMPAIGN

    Institute of Scientific and Technical Information of China (English)

    张丽; 殷子; 刁壁; 任刚; 苏飞; 喻浩; 管庆虎; 詹玮

    2011-01-01

    [目的]建立脊髓灰质炎疫苗(Oral Poliomyelitis Attenuated Live Vaccine,OPV)强化免疫筛选指标体系.[方法]采用文献分析和两轮Delphi专家咨询确立指标体系.运用协调程度、积极系数和权威系数对专家咨询的可靠性进行检验.[结果]两轮专家咨询积极系数为86.67%和83.78%,专家权威程度为0.751,专家意见的协调系数为0.539.建立了包含7个一级指标,25个二级指标组成的OPV强化免疫范围综合评价指标体系.[结沦]专家咨询积极性较高,权威性、协调性较好.建立的评价指标体系可以较全面的对OPV强化免疫工作进行综合评价.%[Objective] To develop a index related to the comprehensive assessment on the Oral Poliomyelitis Attenuated Live Vaccine Supplement Immunization Active. [Methods] Both literature analyses and Delphi method was used to establish the initial evaluation system on OPV mass campaign. Two times of specialists consultation were conducted. And determined the indexes and their weigh. [Results] The enthusiasm coefficient of specialist in two times were 86.67%, 83.78%, respectively. The degree of specialist authority was higher and the average values were 0.751, respectively. The coordination coefficient of specialists' opinion was 0.S39. The comprehensive assessment system on OPV mass campaign was set up, including seven first-class indicators and twenty five sub-indicators. [Conclusion] The enthusiasm, authority, harmony of specialists are good. OPV mass campaign can be evaluated with comprehensive appraisal by the index system of OPV mass campaign which we have established.

  7. Vaccination of rhesus macaques with the live-attenuated HSV-1 vaccine VC2 stimulates the proliferation of mucosal T cells and germinal center responses resulting in sustained production of highly neutralizing antibodies.

    Science.gov (United States)

    Stanfield, Brent A; Pahar, Bapi; Chouljenko, Vladimir N; Veazey, Ronald; Kousoulas, Konstantin G

    2017-01-23

    We have shown that the live-attenuated HSV-1 VC2 vaccine strain with mutations in glycoprotein K (gK) and the membrane protein UL20 is unable to establish latency in vaccinated animals and produces a robust immune response capable of completely protecting mice against lethal vaginal HSV-1 or HSV-2 infections. To better understand the immune response generated by vaccination with VC2, we tested its ability to elicit immune responses in rhesus macaques. Vaccinated animals showed no signs of disease and developed increasing HSV-1 and HSV-2 reactive IgG1 after two booster vaccinations, while IgG subtypes IgG2 and IgG3 remained at low to undetectable levels. All vaccinated animals produced high levels of cross protective neutralizing antibodies. Flow cytometry analysis of cells isolated from draining lymph nodes showed that VC2 vaccination stimulated significant increases in plasmablast (CD27(high)CD38(high)) and mature memory (CD21(-)IgM(-)) B cells. T cell analysis on cells isolated from draining lymph node biopsies demonstrated a statistically significant increase in proliferating (Ki67(+)) follicular T helper cells and regulatory CXCR5(+) CD8(+) cytotoxic T cells. Analysis of plasma isolated two weeks post vaccination showed significant increases in circulating CXCL13 indicating increased germinal center activity. Cells isolated from vaginal biopsy samples collected over the course of the study exhibited vaccination-dependent increases in proliferating (Ki67(+)) CD4(+) and CD8(+) T cell populations. These results suggest that intramuscular vaccination with the live-attenuated HSV-1 VC2 vaccine strain can stimulate robust IgG1 antibody responses that persist for >250days post vaccination. In addition, vaccination lead to the maturation of B cells into plasmablast and mature memory B cells, the expansion of follicular T helper cells, and affects in the mucosal immune responses. These data suggest that the HSV VC2 vaccine induces potent immune responses that could help

  8. Evaluation on Effect of Measles Attenuated Live Vaccine Supplementary Immunization Activities in Fujian Province in 2009%福建省2009年麻疹减毒活疫苗强化免疫活动效果评价

    Institute of Scientific and Technical Information of China (English)

    郑金凤; 蔡志坤; 潘伟毅; 杨秀惠; 陈俊磊

    2011-01-01

    Objective To evaluate the effect of measles attenuated live vaccine (MV)supplementary immunization activities (SIAs)in Fujian province in 2009.Methods Comprehensively anslysing the data of the immunization coverage rate of MY SIAs, antibody level and the data of Measles Surveillance System.Results Total 5 544 453 targeted children of 8 months-14 years old were vaccinated, both reported and survey coverage were >95%, measles IgG antibody positive rate and the GMT level of the population immunized increased significantly.Measles incidence rate decreased to 96.03 % after supplementary immuization activities.The measles annual incidence rate was 0.14/100 000 after immunization between Apr 2009 and Mar 2010.The cases aged ≥ 15 years have a significant increase, the proportion of cases reached by 50.98%.Conclusion The incidence of measles fell to <1/100 000 after MV SIAs In order to remain the achievements of SIA in Fujian province in 2009, the routine immunization coverage rate and continue follow-up campaign should be conducted in time.%目的 评价福建省2009年麻疹减毒活疫苗(Measles Attenuated Live Vaccine,MV)强化免疫活动(Supplementary Immunization Activities,SIA)效果.方法 综合分析SIA接种率、人群抗体水平和麻疹监测系统资料.结果 MV SIA共接种8月龄~14岁目标儿童5 544 453人,报告接种率和调查接种率均>95%,免疫后人群麻疹抗体阳性率和儿何平均滴度显著升高,麻疹发病率较SIA前下降了96.03%.从SIA后1个月算起,1年的时间全人群麻疹发病率为0.14/10万(2009年4月10日~2010年3月31日).但≥15岁病例构成达50.98%.结论 福建省2009年MV SIA效果显著,发病率己降至<1/10万.为保持SIA取得的成果,应在做好常规免疫的基础上,适时开展后续免疫.

  9. A Mumps Outbreak in Vojvodina, Serbia, in 2012 Underlines the Need for Additional Vaccination Opportunities for Young Adults.

    Directory of Open Access Journals (Sweden)

    Jasminka Nedeljković

    Full Text Available In 2012, mumps was introduced from Bosnia and Herzegovina to Vojvodina, causing an outbreak with 335 reported cases. The present manuscript analyses the epidemiological and laboratory characteristics of this outbreak, identifies its main causes and suggests potential future preventive measures. Sera of 133 patients were tested for mumps-specific antibodies by ELISA and 15 nose/throat swabs were investigated for mumps virus RNA by RT-PCR. IgG antibodies were found in 127 patients (95.5%. Mumps infection was laboratory-confirmed in 53 patients, including 44 IgM and 9 PCR positive cases. All other 282 cases were classified as epidemiologically-confirmed. More than half of the patients (n = 181, 54% were 20-29 years old, followed by the 15-19 age bracket (n = 95, 28.4%. Twice as many males as females were affected (67% versus 33%. Disease complications were reported in 13 cases (3.9%, including 9 patients with orchitis and 4 with pancreatitis. According to medical records or anamnestic data, 190 patients (56.7% were immunized with two doses and 35 (10.4% with one dose of mumps-containing vaccine. The Serbian sequences corresponded to a minor genotype G variant detected during the 2011/2012 mumps outbreak in Bosnia and Herzegovina. Vaccine failures, the initial one-dose immunization policy and a vaccine shortage between 1999 and 2002 contributed to the outbreak. Additional vaccination opportunities should be offered to young adults during transition periods in their life trajectories.

  10. Epidemiology of mumps in Changping district in Beijing,2007-2010%2007-2010年北京市昌平区流行性腮腺炎流行病学分析

    Institute of Scientific and Technical Information of China (English)

    王涛; 苑新海; 王海红

    2011-01-01

    目的 了解北京市昌平区流行性腮腺炎(流腮)流行病学特征.方法 利用描述性研究方法,对中国疾病监测信息报告管理系统中报告的流腮病例进行分析.结果 2007 -2010年北京市昌平区共发生流腮病例1196例,年平均发病率为40.59/10万.发病主要集中在2~8岁,占全部病例的67.14%,5岁组发病率最高;发病有明显地区聚集性,回龙观镇、东小口镇和北七家镇等流动人口聚集的城乡结合部发病较高;以学生和托幼儿童发病为主,占全部病例的73.41%;病例发病集中在5-8月;有免疫史发病占66.05%;针对是否发生发热、腮腺疼痛、头痛、双侧腮腺肿大、并发症以及发热和病程持续时间,不同免疫史病例间差异有统计学意义.结论 应加强监测,提高实验室检测能力.腮腺炎疫苗即使不能阻止发病但对减轻流腮临床症状可能有一定作用,同时应对腮腺炎疫苗效力进行深入研究.%Objective To understand the epidemiological characteristics of mumps in Changping in Beijing and provide scientific evidence for the control and prevention of mumps. Methods Descriptive epidemiological analysis was conducted on the incidence data of mumps in Changping collected from national disease reporting information system from 2007 to 2010.. Results A total of 1196 mumps cases occurred in Changping from 2007 to 2010 with the average annual incidence of 40. 59/lakh. Most cases were in age group of 2 - 8 years, accounting for 67. 14% of the total. The incidence in age group of 5 years was highest; The area clustering of the disease was obvious, the incidences were high in townships of Huilongguan, Dongxiaokou and Beiqijia located in zone joining town and country where large number of floating population lived.. Students and children in child care settings were affected mostly, the cases among them accounted for 73.41%. The disease mainly occurred during May-August in a year. The cases in

  11. Comparison of the safety and immunogenicity of live attenuated and inactivated hepatitis A vaccine in healthy Chinese children aged 18 months to 16 years: results from a randomized, parallel controlled, phase IV study.

    Science.gov (United States)

    Ma, F; Yang, J; Kang, G; Sun, Q; Lu, P; Zhao, Y; Wang, Z; Luo, J; Wang, Z

    2016-09-01

    For large-scale immunization of children with hepatitis A (HA) vaccines in China, accurately designed studies comparing the safety and immunogenicity of the live attenuated HA vaccine (HA-L) and inactivated HA vaccine (HA-I) are necessary. A randomized, parallel controlled, phase IV clinical trial was conducted with 6000 healthy children aged 18 months to 16 years. HA-L or HA-I was administered at a ratio of 1: 1 to randomized selected participants. The safety and immunogenicity were evaluated. Both HA-L and HA-I were well tolerated by all participants. The immunogenicity results showed that the seroconversion rates (HA-L versus HA-I: 98.0% versus 100%, respectively, p >0.05), and geometric mean concentrations in participants negative for antibodies against HA virus IgG (anti-HAV IgG) before vaccination did not differ significantly between the two types of vaccines (HA-L versus HA-I first dose: 898.9 versus 886.2 mIU/mL, respectively, p >0.05). After administration of the booster dose of HA-I, the geometric mean concentrations of anti-HAV IgG (HA-I booster dose: 2591.2 mIU/mL) was higher than that after the first dose (p <0.05) and that reported in participants administered HA-L (p <0.05). Additionally, 12 (25%) of the 48 randomized selected participants who received HA-L tested positive for HA antigen in stool samples. Hence, both HA-L and HA-I could provide acceptable immunogenicity in children. The effects of long-term immunogenicity after natural exposure to wild-type HA virus and the possibility of mutational shifts of the live vaccine virus in the field need to be studied in more detail.

  12. Measles, mumps, rubella, and human parvovirus B19 infections and neurologic disease.

    Science.gov (United States)

    Bale, James F

    2014-01-01

    While the systemic disorders associated with measles, mumps, and rubella viruses and human parvovirus B19 tend to be mild, each virus can produce potentially life-threatening neurologic disease in human hosts, especially when these viruses infect young children. Two of the viruses, rubella and parvovirus B19, can be vertically transmitted to fetuses during maternal infection and cause congenital infection. Neurologic complications are common after intrauterine infection with the rubella virus, a condition known as the congenital rubella syndrome. Two, measles and rubella viruses, can induce "slow viral" infections, serious, disorders that can occur several years after the initial exposure to the virus and typically have fatal outcomes.

  13. The Meta-Analysis of Vaccine Protective Efficacy of Oral Rotavirus Attenuated Live Vaccine%口服轮状病毒减毒活疫苗保护效果研究Meta分析

    Institute of Scientific and Technical Information of China (English)

    胡昱; 李倩; 陈恩富; 戚小华; 陈雅萍

    2012-01-01

    目的 评价口服轮状病毒减毒活疫苗(Oral Rotavirus Attenuated Live Vaccine,ORV)的流行病学保护效果.方法 电子检索《中国生物医学文献数据库》、《中国期刊全文数据库》、《万方全文数据库》、National Center for Biotechnology Information (NCBI)(《美国国家医学图书馆数据库》)、《Cochrane(考柯兰)协作网图书馆》等数据库,将有关接种ORV流行病学保护效果的研究纳入分析.使用Rev Man4.2.10软件进行统计分析.结果 共纳入14篇文献,有6项为随机对照试验研究,8项为队列研究.单价兰州羊(Monovalent Lanzhou Lamb) ORV (ORV-L)对轮状病毒胃肠炎( Rotavirus Gastroenteritis,RVGE)的保护率为76% [95%可信区间(Confidence Interval,CI):67%~83%];单价人(Monovalent Human)ORV (ORV-H)和五价人-牛重配(Pentavalent Human-Bovine Reassortant)ORV(ORV-HB)对RVGE、严重(Severe) RVGE (SRVGE)和住院率(Hospitalized rate)的合并保护率分别为61% (95%CI:28%~79%)、71% (95%CI:44%~85%)和88% (95%CI:67%~96%).7篇文献报道了ORV的安全性,无严重不良反应和死亡报告.结论 接种不同种类的ORV可以不同程度地降低RVGE的发病,减少SRVGE和降低AR,具有良好的保护效果.%Objective To evaluate vaccine protective efficacy (VE) of oral rotavirus attenuated live vaccine(ORV) used in China. Methods Searching "China Biology Medicine disc,CBMd", "China National Knowledge Infrastructure, CNKI", "Wanfang Database, WF" database, "National Center for Biotechnology Information, NCBI"," Cochrane Library,CL", the studies of VE for ORV were included, and meta analysis were made by RevMan4.2.10 software. Results A total of 14 studies were included, 6 studies were random clinic trial (RCT), 8 studies were cohort studies. The VE of monovalent Lanzhou lamb rotavirus vaccine(ORV-L) against rotavirus gastroenteritis(RVGE) was 76% [95% (confidence interval, C/) :61% ~83% ]. The combined VE of monovalent

  14. An Epidemiological Study on Measles Cases with Vaccination History of Measles Attenuated Live Vaccine%有麻疹减毒活疫苗接种史的麻疹病例流行病学分析

    Institute of Scientific and Technical Information of China (English)

    赵艳荣; 陈恩富; 李倩; 蒋征刚; 何寒青; 凌罗亚

    2011-01-01

    Objective To know the distribution characteristics of measles cases with vaccination history of measles attenuated live vaccine (MV ) and to provide base data for Measles control and prevention. Methods A descriptive epidemiological study was conducted to analyze measles cases with or without vaccination history of measles attenuated vaccine reported in Zhejiang province in 2009. Results The confirmed measles cases with vaccination history of measles vaccine was obviously lower than (16.44% ) non-measles cases (41.45%). The shortest interval between the latest MV vaccination and onset of measles case was Od, the longest is 25 years, with a median of 3 months. The occurrence of Measles of interval proportions <1 month, 1-11 months, 1-9 years, 10-25 years were 42.10%, 30.19%, 19.50%, 6.92% respectively. The interval distribution was different by age groups. Some symptoms were milder in the cases with MV history than that without MV history. For cases with different interval between recent MV vaccination and onset of measles, conjunctivitis was less in those of 6-10d than others. Conclusion Measles cases with MV history could be resulted from primary or secondary immunization failure, or time vaccinated at the late incubation period. Few cases may actually be vaccine reactions at 6-10d after vaccination.%目的 了解有麻疹减毒活疫苗(Measles Attenuated Live Vaccine,MV)接种史的麻疹病例的分布特点,为查找原因及提出控制措施提供基础数据.方法 对浙江省2009年报告的有、无MV接种史的麻疹病例进行描述流行病学分析.结果 麻疹确诊病例中,有MV接种史的比例(16.44%)明显低于非麻疹病例(41.45%).末次接种距发病最短间隔为0d,最长为25年,中位数为3个月.接种后<1个月、1~11个月、1~9年、10~25年的发病构成分别为42.10%、30.19%、19.50%、6.92%,不同年龄组末次接种距发病时间分布不同.有MV接种史的麻疹病例与无接种史者相比

  15. Evaluation of Psn, HmuR and a modified LcrV protein delivered to mice by live attenuated Salmonella as a vaccine against bubonic and pneumonic Yersinia pestis challenge.

    Science.gov (United States)

    Branger, Christine G; Sun, Wei; Torres-Escobar, Ascención; Perry, Robert; Roland, Kenneth L; Fetherston, Jacqueline; Curtiss, Roy

    2010-12-16

    We evaluated the ability of Yersinia pestis antigens HmuR, Psn and modified forms of LcrV delivered by live attenuated Salmonella strains to stimulate a protective immune response against subcutaneous or intranasal challenge with Y. pestis CO92. LcrV196 is a previously described truncated protein that includes aa 131-326 of LcrV and LcrV5214 has been modified to replace five key amino acids required for interaction with the TLR2 receptor. Psn is the outer membrane receptor for the siderophore, yersiniabactin, and the bacteriocin, pesticin. Mice immunized with Salmonella synthesizing Psn, LcrV196 or LcrV5214 developed serum IgG responses to the respective Yersinia antigen and were protected against pneumonic challenge with Y. pestis. Immunization with Salmonella synthesizing Psn or LcrV196 was sufficient to afford nearly full protection against bubonic challenge, while immunization with the strain synthesizing LcrV5214 was not protective. Immunization with Salmonella synthesizing HmuR, an outer membrane protein involved in heme acquisition in Y. pestis, was poorly immunogenic and did not elicit a protective response against either challenge route. These findings indicate that both Psn and LcrV196 delivered by Salmonella provide protection against both bubonic and pneumonic plague. Copyright © 2010 Elsevier Ltd. All rights reserved.

  16. Comparison of a live attenuated Salmonella Enteritidis vaccine candidate secreting Escherichia coli heat-labile enterotoxin B subunit with a commercial vaccine for efficacy of protection against internal egg contamination by Salmonella in hens.

    Science.gov (United States)

    Nandre, Rahul M; Eo, Seong Kug; Park, Sang Youel; Lee, John Hwa

    2015-07-01

    This study compared a new live attenuated Salmonella Enteritidis vaccine candidate secreting Escherichia coli heat-labile enterotoxin B subunit (SE-LTB) with a commercial Salmonella Enteritidis (SE) vaccine for efficacy of protection against SE infection in laying hens. Chickens were divided into 3 groups of 20 each. Group A chickens were inoculated orally with phosphate-buffered saline and served as controls, group B chickens were inoculated orally with the vaccine candidate, and group C chickens were inoculated intramuscularly with a commercial vaccine, the primary inoculation in groups B and C being at 10 wk of age and the booster at 16 wk. Groups B and C showed significantly higher titers of plasma immunoglobulin G, intestinal secretory immunoglobulin A, and egg yolk immunoglobulin Y antibodies compared with the control group, and both vaccinated groups showed a significantly elevated cellular immune response. After virulent challenge, group B had significantly lower production of thin-shelled and/or malformed eggs and a significantly lower rate of SE contamination of eggs compared with the control group. Furthermore, the challenge strain was detected significantly less in all of the examined organs of group B compared with the control group. Group C had lower gross lesion scores only in the spleen and had lower bacterial counts only in the spleen, ceca, and ovary. These findings indicate that vaccination with the SE-LTB vaccine candidate can efficiently reduce internal egg and internal organ contamination by Salmonella and has advantages over the commercial vaccine.

  17. Safety and immunogenicity of escalating dosages of a single oral administration of peru-15 pCTB, a candidate live, attenuated vaccine against enterotoxigenic Escherichia coli and Vibrio cholerae.

    Science.gov (United States)

    Chen, Wilbur H; Garza, Jose; Choquette, Monique; Hawkins, Jennifer; Hoeper, Amy; Bernstein, David I; Cohen, Mitchell B

    2015-01-01

    Enterotoxigenic Escherichia coli (ETEC) organisms are a leading cause of infectious diarrhea in developing countries. A live, attenuated cholera strain that expresses high levels of the nontoxic B subunit of cholera toxin, which might also serve as an ETEC protective antigen, was evaluated for safety, excretion, and immunogenicity in healthy volunteers. We enrolled four inpatient dose-escalation cohorts of 15 to 16 eligible subjects to randomly (3:1) receive a single oral dose of vaccine or placebo (buffer alone), evaluating 1 ×10(7), 1 ×10(8), 1 ×10(9), and 1 ×10(10) CFU of the vaccine. The vaccine was well tolerated, although some subjects experienced moderate diarrhea. The serum Inaba vibriocidal antibody response appeared to display a dose-response relationship with increasing dosages of vaccine, plateauing at the 10(9)-CFU dosage. The serum antitoxin (cholera toxin and heat-labile enterotoxin) antibody seroconversion rate (4-fold increase over baseline) also appeared to display a dose-response relationship. The vaccine strain was excreted in stool cultures, displaying a dose-response relationship. A single oral dose of Peru-15 pCTB at dosages up to 1 ×10(10) CFU was safe and immunogenic in this first-in-human trial. These encouraging data support the ongoing clinical development of this candidate combined cholera and ETEC vaccine. (This study has been registered at ClinicalTrials.gov under registration no. NCT00654108.).

  18. Mumps epidemiology in the mid-west of Ireland 2004-2008: increasing disease burden in the university/college setting.

    LENUS (Irish Health Repository)

    Whyte, D

    2009-01-01

    Mumps is a contagious vaccine-preventable viral disease that is experiencing a revival in students attending second and third level colleges. Large mumps outbreaks have been reported in several countries despite the presence of childhood immunisation programmes over many years, including measles, mumps, and rubella (MMR) vaccination. In 2008, 1,377 cases of mumps were notified in Ireland and 1,734 in the first three months of 2009 (provisional data). This paper reviews the recent epidemiology of mumps in the Mid-West region of Ireland and highlights preventive measures. A substantial proportion of cases were not laboratory-confirmed and it is important that doctors continue to notify suspected cases. In the Irish Mid-West, data from enhanced surveillance shows a high proportion of mumps in the age group 15-24 years. Complications were uncommon and rarely severe. Where data were available, over half of the cases did not recall having received two doses of MMR, but most recalled one dose. Parents should continue to ensure children receive both MMR vaccinations so that uptake is optimal for protection. Steps were taken to increase awareness of the disease in the school, college and university settings. Preventive measures implemented to limit mumps transmission in the school\\/college setting over recent years included vaccination of close contacts, isolation for five days and hand hygiene.

  19. Mumps epidemiology in the mid-west of Ireland 2004-2008: increasing disease burden in the university/college setting.

    Science.gov (United States)

    Whyte, D; O'Dea, F; McDonnell, C; O'Connell, N H; Callinan, S; Brosnan, E; Powell, J; Monahan, R; FitzGerald, R; Mannix, M; Greally, T; Dee, A; O'Sullivan, P

    2009-04-23

    Mumps is a contagious vaccine-preventable viral disease that is experiencing a revival in students attending second and third level colleges. Large mumps outbreaks have been reported in several countries despite the presence of childhood immunisation programmes over many years, including measles, mumps, and rubella (MMR) vaccination. In 2008, 1,377 cases of mumps were notified in Ireland and 1,734 in the first three months of 2009 (provisional data). This paper reviews the recent epidemiology of mumps in the Mid-West region of Ireland and highlights preventive measures. A substantial proportion of cases were not laboratory-confirmed and it is important that doctors continue to notify suspected cases. In the Irish Mid-West, data from enhanced surveillance shows a high proportion of mumps in the age group 15-24 years. Complications were uncommon and rarely severe. Where data were available, over half of the cases did not recall having received two doses of MMR, but most recalled one dose. Parents should continue to ensure children receive both MMR vaccinations so that uptake is optimal for protection. Steps were taken to increase awareness of the disease in the school, college and university settings. Preventive measures implemented to limit mumps transmission in the school/college setting over recent years included vaccination of close contacts, isolation for five days and hand hygiene.

  20. Application of Oral Fluid Assays in Support of Mumps, Rubella and Varicella Control Programs

    Directory of Open Access Journals (Sweden)

    Peter A. C. Maple

    2015-12-01

    Full Text Available Detection of specific viral antibody or nucleic acid produced by infection or immunization, using oral fluid samples, offers increased potential for wider population uptake compared to blood sampling. This methodology is well established for the control of HIV and measles infections, but can also be applied to the control of other vaccine preventable infections, and this review describes the application of oral fluid assays in support of mumps, rubella and varicella national immunization programs. In England and Wales individuals with suspected mumps or rubella, based on clinical presentation, can have an oral fluid swab sample taken for case confirmation. Universal varicella immunization of children has led to a drastic reduction of chickenpox in those countries where it is used; however, in England and Wales such a policy has not been instigated. Consequently, in England and Wales most children have had chickenpox by age 10 years; however, small, but significant, numbers of adults remain susceptible. Targeted varicella zoster virus (VZV immunization of susceptible adolescents offers the potential to reduce the pool of susceptible adults and oral fluid determination of VZV immunity in adolescents is a potential means of identifying susceptible individuals in need of VZV vaccination. The main application of oral fluid testing is in those circumstances where blood sampling is deemed not necessary, or is undesirable, and when the documented sensitivity and specificity of the oral fluid assay methodology to be used is considered sufficient for the purpose intended.

  1. Acetaminophen (Paracetamol) Use, Measles-Mumps-Rubella Vaccination, and Autistic Disorder: The Results of a Parent Survey

    Science.gov (United States)

    Schultz, Stephen T.; Klonoff-Cohen, Hillary S.; Wingard, Deborah L.; Akshoomoff, Natacha A.; Macera, Caroline A.; Ji, Ming

    2008-01-01

    The present study was performed to determine whether acetaminophen (paracetamol) use after the measles-mumps-rubella vaccination could be associated with autistic disorder. This case-control study used the results of an online parental survey conducted from 16 July 2005 to 30 January 2006, consisting of 83 children with autistic disorder and 80…

  2. Antibody responses to Hepatitis B and measles-mumps-rubella vaccines in children who received chemotherapy for acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Simone Santana Viana

    2012-01-01

    Full Text Available OBJECTIVE: To evaluate viral vaccine antibody levels in children with acute lymphoblastic leukemia after chemotherapy and after vaccine booster doses. METHODS: Antibody levels against hepatitis B, rubella, measles and mumps vaccine antigens were evaluated in 33 children after completing chemotherapy (before and after vaccine booster doses and the results were compared to the data of 33 healthy children matched for gender, age and social class. RESULTS: After chemotherapy, 75.9%, 67.9%, 59.3% and 51.7% of the patients showed low antibody titers that would be unlikely to protect against exposure to measles, rubella, hepatitis B and mumps, respectively. After receiving a vaccine booster dose for these antigens the patients had high antibody levels consistent with potential protection against measles, mumps and hepatitis B, but not against rubella. CONCLUSION: Extra doses of measles-mumps-rubella plus hepatitis B vaccines are recommended in acute lymphoblastic leukemia patients submitted to treatment after hematologic recovery. After this, viral vaccine antibody levels should be verified to define the individual's protective status.

  3. Acetaminophen (Paracetamol) Use, Measles-Mumps-Rubella Vaccination, and Autistic Disorder: The Results of a Parent Survey

    Science.gov (United States)

    Schultz, Stephen T.; Klonoff-Cohen, Hillary S.; Wingard, Deborah L.; Akshoomoff, Natacha A.; Macera, Caroline A.; Ji, Ming

    2008-01-01

    The present study was performed to determine whether acetaminophen (paracetamol) use after the measles-mumps-rubella vaccination could be associated with autistic disorder. This case-control study used the results of an online parental survey conducted from 16 July 2005 to 30 January 2006, consisting of 83 children with autistic disorder and 80…

  4. 国产甲型肝炎减毒活疫苗和灭活疫苗安全性评价%Evaluation on Safety of Domestic Hepatitis A Attenuated Live Vaccine and Hepatitis A Inactivated Vaccine

    Institute of Scientific and Technical Information of China (English)

    张晓曙; 安婧; 刘建锋; 付鸿; 高丽; 李慧

    2012-01-01

    Objective To evaluate safety of domestic hepatitis A attenuated live vaccine (HepA-L) and hepatitis A inactivated vaccine (HepA-I), and provide reference for emergency vaccination after hepatitis A outbreaks. Methods 493 children aged 6-9 years confirmed negative with antibody to hepatitis A virus (Anti-HAV) produced by Abbott. U.S were divided randomly into four groups. Group A were vaccinated with domestic HepA-L, group B were vaccinated with domestic HepA-I, group C were vaccinated with hepatitis B vaccine made by recombinant deoxyribonucleic acid technigues in sacchararomyces cerevisiae yeast ( HepB-SCY ) as negative control and group D were vaccinated HepA-I produced by GlaxoSmithKline Biologicals S.A. (GSK)as positive control. The adverse events following immunization (AEFIs) were observed after 30 minutes, 24, 48 and 72 hours after vaccination with double-blind method. Results The main AEFIs were fever, local pain and scleroma. There were no other severe AEFIs. The rate of AEFIs was 13.95% in Group A, 15.25% in group B, 16.80% in group C and 25.62% in group D. There were no statistical differences between different groups (x2=6.953, P=0.073). Conclusion Domestic HepA-L, domestic HepA-I and imported HepA-I are Safe.%目的 评价国产甲型病毒性肝炎(甲肝)减毒活疫苗(Hepatitis A Attenuated Live Vaccine,HepA-L)和灭活疫苗(Hepatitis A Inactivated Vaccine,HepA-I)的安全性,为开展甲肝爆发疫情应急接种提供参考.方法 用美国雅培(Abbott)公司生产的抗甲肝病毒抗体(Antibody to Hepatitis A Virus,Anti-HAV)试剂,筛查未感染HAV的6~9岁儿童.将入选对象随机分为4组,分别接种国产HepA-L和国产HepA-I,以国产的重组乙型肝炎疫苗(酿酒酵母)(Hepatitis B Vaccine Made by Recombinant Deoxyribonucleic Acid Technigues in Sacchararomyces Cerevisiae Yeast,HepB-SCY)为阴性对照,以GlaxoSmithKline Biologicals S.A.(GSK)生产的HepA-I为阳性对照,采取随机双盲方法,观察接种疫苗后30min

  5. Analysis on effectiveness of measles attenuated live vaccine supplementary immunization activities in Nanchang at 2009%南昌市2009年麻疹减毒活疫苗强化免疫活动效果分析

    Institute of Scientific and Technical Information of China (English)

    廖征; 彭时辉; 文海蓉; 张艳霞; 熊昌辉

    2012-01-01

    目的 评价2009年南昌市麻疹减毒活疫苗(Measles Attenuated Live Vaccine,MV)强化免疫活动(SupplementaryImmunization Activities,SLA)效果,为消除麻疹提供依据.方法 对南昌市2009年10月麻疹疫苗强化免疫期间的摸底调查、现场接种、评估报告等资料和强化免疫前后的中国疾病预防控制信息系统中麻疹疫情资料进行综合分析.结果 该次强化免疫共接种目标儿童988959剂次,报告接种率为97.91%(988959/1010096),快速评估调查接种率为96.94%(1745/1800);MV SIA后人群麻疹抗体阳性率、保护率分别为91.99%、70.83%,抗体GMT从免疫前的1∶555上升到免疫后的1∶1625.28,免疫前后人群麻疹抗体GMT差异有统计学意义(t=4.795,P=0.000).本次强化免疫共报告疑似预防接种异常反应(Adverse Events Following Immunization,AEFI)25例,发生率为2.53/10万;强化免疫后的2009年11月~2010年10月全市报告麻疹病例10例,发病率为0.20/10万,较2008年11月~2009年10月同期病例明显减少.结论 高质量的MV SIA能迅速提高人群的抗体水平,降低麻疹发病率,适时开展MV SIA是加速麻疹控制最安全有效的措施之一.%Objective To evaluate the effectiveness of measles attenuated live vaccine (MV) supplementary immunization activities (SIA) in Nanchang in 2009 and provide basis for elimination measles. Method Collecting the data of basic investigation, scene vaccination and evaluation reports during measles vaccine supplementary immunization time of October 2009, all them comprehensive analysis with the data before and after supplementary immunization which collected from China Disease Prevention and Control Information System. Results This supplementary immunization had inoculation goal children 988 959 times, the reporting inoculation rate was 97.91% (988 959/1 010 096), the rapid assessment survey inoculation rate was 96. 94% (1 745/1 800) . MV SIA measles antibody positive rate, protection

  6. Measles, mumps, and rubella antibody status and response to immunization in children after therapy for acute lymphoblastic leukemia.

    Science.gov (United States)

    Aytac, Selin; Yalcin, S Songul; Cetin, Mualla; Yetgin, Sevgi; Gumruk, Fatma; Tuncer, Murat; Yurdakok, Kadriye; Gurgey, Aytemiz

    2010-08-01

    Seventy-seven patients with acute lymphoblastic leukemia (ALL) who were in complete remission and whose therapies had been stopped for at least 6 months before enrollment in this study were retrospectively analyzed regarding their antibody status for measles, mumps, and rubella, with the aim to demonstrate the seropositivity rate after treatment in the authors' group. Each patient's serum samples were analyzed by enzyme-linked immunosorbent assay (ELISA) method to determine the antibody titers before and after immunization. Measles serology was available in 77 children; 45 (58%) were seronegative. Initial ages of measle-seronegative patients were statistically lower than those of seropositive cases (median 3.29 versus 4.91 years, respectively). Mumps serology was available in 76 children; 36 (47%) were seronegative. Mumps-seropositive cases tended to have more frequent previous history of infection than seronegative cases (55.0% versus 28.6%, respectively, P = .05). Rubella serology was available in 76 children, and 20 (26.3%) were seronegative. It was determined that initial ages of rubella-seronegative patients were statistically lower than those of seropositive cases (median 3.03 versus 4.32 years, respectively). The authors concluded based on the results of their study that at a median of 3.31 years after completion of chemotherapy for ALL, the majority of cases had antibody levels lower than protective values for measles (58.4%); however, these values were 47.3% for mumps and 26.3% for rubella. Seroconversion rates after measles (55%) and mumps vaccination (57.1%) were still low. However, in the available cases, relatively adequate response to rubella vaccination (92.3%) was observed.

  7. Similar immunogenicity of measles-mumps-rubella (MMR) vaccine administrated at 8 months versus 12 months age in children.

    Science.gov (United States)

    He, Hanqing; Chen, Enfu; Chen, Haiping; Wang, Zhifang; Li, Qian; Yan, Rui; Guo, Jing; Zhou, Yang; Pan, Jinren; Xie, Shuyun

    2014-06-30

    Two doses of measles-mumps-rubella (MMR) strategy has been recommended by World Health Organization and is also widely adopted in many countries. In order to provide the evidence for perfecting the immunization strategy of MMR, this study evaluated the safety and immunogenicity of MMR with different two-dose schedule in infants. 280 participants were enrolled and randomly allocated to Group 1 (first dose at 8 months) or Group 2 (first dose at 12 months), and both groups administered the second dose at 10 months later. Solicited local and general symptoms after each vaccination with MMR were mild and infrequent in all participants of two groups. After administration of the first dose of MMR, seropositive rates were 100% in both groups for measles, 89.3% in Group 1 and 87.1% in Group 2 for mumps (P=0.578), 92.0% in Group 1 and 92.9% in Group 2 (P=0.393). The seropositive rates of mumps decreased significantly (from >86% to measles and rubella. All children get the positive titer for three vaccines in two groups after given the second dose MMR, higher seroconversion rate was found for mumps both in two groups (71.7% vs 77.2%, P=0.370). In conclusion, this study indicated that the MMR was well tolerated and immunogenic against measles, mumps and rubella with schedule of first dose both at 8 months and 12 months age. Our findings strongly supported that two doses of MMR can be introduced by replacing the first dose of MR in current EPI with MMR at 8 months age and the second dose at 18 months in China.

  8. Evaluation of different continuous cell lines in the isolation of mumps virus by the shell vial method from clinical samples

    Science.gov (United States)

    Reina, J; Ballesteros, F; Mari, M; Munar, M

    2001-01-01

    Aims—To compare prospectively the efficacy of the Vero, LLC-MK2, MDCK, Hep-2, and MRC-5 cell lines in the isolation of the mumps virus from clinical samples by means of the shell vial method. Methods—During an epidemic outbreak of parotiditis 48 clinical samples (saliva swabs and CSF) were studied. Two vials of the Vero, LLC-MK2, MDCK, MRC-5, and Hep-2 cell lines were inoculated with 0.2 ml of the samples by the shell vial assay. The vials were incubated at 36°C for two and five days. The vials were then fixed with acetone at -20°C for 10 minutes and stained by a monoclonal antibody against mumps virus by means of an indirect immunofluorescence assay. Results—The mumps virus was isolated from 36 samples. The Vero and LLC-MK2 cell lines showed a 100% isolation capacity, MDCK showed 77.7%, MRC-5 showed 44.4%, and Hep-2 showed 22.2%. The Vero and LLC-MK2 lines were significantly different to the other cell lines (p 5 infectious foci) were 94.4% for Vero, 97.2% for LLC-MK2, 5.5% for MDCK, 5.5% for Hep-2, and 0% for MRC-5. Conclusions—The Vero and LLC-MK2 cell lines are equally efficient at two and five days incubation for the isolation of the mumps virus from clinical samples, and the use of the shell vial method considerably shortens the time of aetiological diagnosis with higher specificity. Key Words: mumps virus • Vero cell line • LLC-MK2 cell line • MDCK cell line • Hep-2 cell line • MRC-5 cell line • isolation • shell vial PMID:11729211

  9. Lot-to-lot consistency of live attenuated SA 14-14-2 Japanese encephalitis vaccine manufactured in a good manufacturing practice facility and non-inferiority with respect to an earlier product.

    Science.gov (United States)

    Zaman, K; Naser, Abu Mohd; Power, Maureen; Yaich, Mansour; Zhang, Lei; Ginsburg, Amy Sarah; Luby, Stephen P; Rahman, Mahmudur; Hills, Susan; Bhardwaj, Mukesh; Flores, Jorge

    2014-10-21

    We conducted a four-arm, double-blind, randomized controlled trial among 818 Bangladeshi infants between 10 and 12 months of age to establish equivalence among three lots of live attenuated SA 14-14-2 JE vaccine manufactured by the China National Biotec Group's Chengdu Institute of Biological Products (CDIBP) in a new Good Manufacturing Practice (GMP) facility and to evaluate non-inferiority of the product with a lot of the same vaccine manufactured in CDIBP's original facility. The study took place in two sites in Bangladesh, rural Matlab and Mirpur in urban Dhaka. We collected pre-vaccination (Day 0) and post-vaccination Day 28 (-4 to +14 days) blood samples to assess neutralizing anti-JE virus antibody titers in serum by plaque reduction neutralization tests (PRNT). Seroprotection following vaccination was defined as a PRNT titer ≥1:10 at Day 28 in participants non-immune at baseline. Follow-up for reactogenicity and safety was conducted through home visits at Day 7 and monitoring for serious adverse events through Day 28. Seroprotection rates ranged from 80.2% to 86.3% for all four lots of vaccine. Equivalence of the seroprotection rates between pairs of vaccine lots produced in the new GMP facility was satisfied at the pre-specified 10% margin of the 95% confidence interval (CI) for two of the three pairwise comparisons, but not for the third (-4.3% observed difference with 95% CI of -11.9 to 3.3%). Nevertheless, the aggregate seroprotection rate for all three vaccine lots manufactured in the GMP facility was calculated and found to be within the non-inferiority margin (within 10%) to the vaccine lot produced in the original facility. All four lots of vaccine were safe and well tolerated. These study results should facilitate the use of SA 14-14-2 JE vaccine as a routine component of immunization programs in Asian countries.

  10. Attenuated Shigella flexneri 2a ΔguaBA Strain CVD 1204 Expressing Enterotoxigenic Escherichia coli (ETEC) CS2 and CS3 Fimbriae as a Live Mucosal Vaccine against Shigella and ETEC Infection

    Science.gov (United States)

    Altboum, Zeev; Barry, Eileen M.; Losonsky, Genevieve; Galen, James E.; Levine, Myron M.

    2001-01-01

    To construct a prototype hybrid vaccine against Shigella and enterotoxigenic Escherichia coli (ETEC), the genes encoding the production of ETEC CS2 and CS3 fimbriae were isolated and expressed in attenuated Shigella flexneri 2a guaBA strain CVD 1204. The CS2 cotA to -D genes, isolated from ETEC strain C91F, and the CS3 cstA to -H genes, subcloned from plasmid pCS100, were cloned into ∼15-copy-number-stabilized pGA1 behind the osmotically regulated ompC promoter, resulting in high expression of both fimbriae. Under nonselective in vitro growth conditions, pGA1-CS2 and pGA1-CS3 were stable in CVD 1204, exhibiting a plasmid loss of only approximately 1% per duplication. Expression of CS2 and CS3 reduced the invasiveness of Shigella for HeLa cells and slowed the intracellular growth rate. Guinea pigs immunized intranasally with CVD 1204(pGA1-CS2) or CVD 1204(pGA1-CS3), or with a mixture of these strains, developed secretory immunoglobulin A (IgA) in tears and serum IgG antibodies against Shigella lipopolysaccharide, CS2, and CS3 antigens. Moreover, the animals were protected against keratoconjunctivitis following conjunctival challenge with virulent S. flexneri 2a strain 2457T. Animals immunized with Shigella expressing CS2 or CS3 developed serum antibodies that agglutinated Shigella as well as an ETEC strain bearing the homologous fimbriae, whereas animals immunized with combined CVD 1204(pGA1-CS2) and CVD 1204(pGA1-CS3) developed antibodies that agglutinated all three test strains. These observations support the feasibility of a multivalent vaccine against shigellosis and ETEC diarrhea consisting of multiple Shigella live vectors expressing relevant ETEC antigens. PMID:11292735

  11. 中国水痘减毒活疫苗接种的成本效益初步分析%Initial Economic Evaluation of Immunization of Freeze-dried Varicella Attenuated Live Vaccine in China

    Institute of Scientific and Technical Information of China (English)

    殷大鹏; 沈心亮; 高青林; 梁晓峰; 罗林云; 宋立志; 张晓曙; 李放军; 过琴媛; 曹玲生; 刘燕敏; 夏伟

    2011-01-01

    Objective To analyze cost-benefit of VarV immunization in China except Hongkang,Makco Special Administrative Region (SAR), and Taiwan Sheng. Method Base on Holloran model and modified parameters, the epidemiological trend of varicella was deduced in a period of 50 years. The cost-benefit analysis was carried out with previous study of disease burden. Result The cost-benefit of one dose of routine varicella vaccine is 1:4.19, and one dose routine immunization plus Supplementary Immunization Activities (SIAs) is about 1:3.57. Conclusion Considering the impact of vaccination on morbidity and costs, a routine childhood vaccination program against varicella is worthwhile in China.%目的 了解中国(未包括香港、澳门特别行政区和台湾地区)水痘减毒活疫苗(Varicella Attenuated Live Vaccine,VarV)接种的成本效益.方法 采用Halloran哈罗)建立的模型,通过查阅文献,对模型参数进行修正,推算中国在2007年后进行VarV常规免疫后的水痘流行病学规律.并利用既往疾病负担数据,对中国VarV接种的成本效益进行初步分析.结果 一剂VarV常规免疫的成本效益比是1:4.19,常规免疫和强化免疫相结合的免疫策略成本效益比是1:3.57.结论 考虑到接种对费用和死亡病例的影响,中国进行VarV的常规免疫是有价值的.

  12. Living in Living Cities

    CERN Document Server

    Gershenson, Carlos

    2011-01-01

    This paper presents and overview of current and potential applications of living technology to urban problems. Living technology can be described as technology that exhibits the core features of living systems. These features can be useful to solve dynamic problems. In particular, urban problems concerning mobility, logistics, telecommunications, governance, safety, sustainability, and society and culture are presented, while solutions involving living technology are reviewed. Finally, the usefulness of describing cities as living systems is discussed.

  13. Clinical observation of epithelial herpes simplex keratitis treated by live attenuated measles vaccine%麻疹减毒活疫苗治疗上皮型单纯疱疹病毒性角膜炎临床观察

    Institute of Scientific and Technical Information of China (English)

    于静; 张明昌; 向其元

    2012-01-01

    目的 探讨麻疹减毒活疫苗治疗上皮型单纯疱疹病毒性角膜炎(HSK)的临床效果.方法 选取在钟祥市人民医院眼科门诊确诊的60例(60眼)上皮型HSK患者,随机分为对照组和试验组,每组30例.对照组给予更昔洛韦滴眼液滴眼,每日8次;试验组球结膜下注射麻疹减毒活疫苗,隔日1次,每次0.5 mL,联合更昔洛韦滴眼液滴眼,每日8次,治疗3周.观察治疗后1、2、3周的治疗效果,随访2a,观察其复发率.结果 对照组在治疗后第1、2、3周的症状与体征评分分别为2.533±0.507、2.133±0.730、1.433±0.728,试验组分别为2.200±0.252、1.800±0.761、1.067±0.254,2组各相应时间点评分比较差异均有统计学意义(P<0.05);治疗后第1、2、3周2组间各时间对应点角膜知觉情况比较差异有统计学意义(P<0.05).对照组在治疗后第2、3周眼部炎症反应的治愈率分别为13.33% (4/30)、26.67%(8/30),试验组分别为33.33% (10/30)、66.67% (20/30),2组比较差异有统计学意义(P<0.05).随访2a,对照组复发率为26.67%,试验组为6.67%,2组比较差异有统计学意义(P<0.05)).2组患者均未出现明显不良反应.结论 应用更昔洛韦滴眼液联合麻疹减毒活疫苗球结膜下注射治疗上皮型HSK具有治愈率高、不良反应少、复发率低等优点.%Objective To investigate clinical effect of epithelial herpes simplex keratitis( HSK) treated by live attenuated measles vaccine. Methods Sixty epithelial HSK patients diagnosed at Zhongxiang people's hospital were enrolled. All the patients were divided into control group and experimental group randomly ,30 patients in each group. The control group patients were treated by ganciclovir eye drops,8 times per day,while experimental group patients were treated by ganciclovir eye drops (8 times per day) as well as sub-conjunctival injection oflive attenuated measles vaccine(0.5 mL per time, every other day). All patients were treated

  14. Overview of measles and mumps vaccine: origin, present, and future of vaccine production.

    Science.gov (United States)

    Betáková, T; Svetlíková, D; Gocník, M

    2013-01-01

    Measles and mumps are common viral childhood diseases that can cause serious complications. Vaccination remains the most efficient way to control the spread of these viruses. The manufacturing capability for viral vaccines produced in embryonated hen eggs and conventional/classical cell substrates, such as chicken embryo fibroblast or primary dog kidney cell substrates, is no longer sufficient. This limitation can be overcome by utilizing other recognized cell substrates such as Madin Darby Canine Kidney (MDCK), Chinese Hamster Ovary (CHO), Vero (monkey origin) cells, MRC-5 (human diploid) or as an alternative, introducing new cell substrates of human or avian origin. A very important factor in vaccine production is the safety and immunogenicity of the final vaccine, where the proper choice of cell substrate used for virus propagation is made. All substrates used in vaccine production must be fully characterized to avoid the contamination of hidden unknown pathogens which is difficult to achieve in primary cell substrates.

  15. Effect of multiple freeze-thaw cycles on detection of measles, mumps, and rubella virus antibodies.

    Science.gov (United States)

    Pinsky, Norman A; Huddleston, Jeanne M; Jacobson, Robert M; Wollan, Peter C; Poland, Gregory A

    2003-01-01

    We investigated the effect of multiple freeze-thaw cycles on mumps, measles, and rubella virus serum antibody levels with whole-virus immunoglobulin G enzyme-linked immunoassays. Fresh serum samples from nine healthy adult volunteers were divided into six sets of five aliquots each. Samples were taken through a total of 10 freeze-thaw cycles and stored at 4 degrees C until assayed. Each assay measurement was done in replicates of five, and the mean value was reported. After completing 10 freeze-thaw cycles, we found no clinically or statistically significant effect on measured antibody levels and found no discernible detrimental effect on the ability to measure these antibodies by enzyme-linked immunoassays.

  16. Design of PolyMUMPS device for diabetes screening via acetone vapor detection in exhaled breath

    Science.gov (United States)

    Rabih, Almur A. S.; Dennis, J. O.; Khir, M. H. Md; Ahmed, Mawahib Gafare; Mian, Muhammad Umer

    2016-11-01

    Diabetes is a chronic disease that occurs due to deficiency or improper use of insulin by body tissues. It is currently diagnosed invasively by measuring blood glucose. This paper reports modelling and simulation of a PolyMUMPS device proposed for a non-invasive screening of diabetes. The device is electromagnetically driven at its resonance frequency using Lorenz force, while the output is detected by capacitive means. The resonance frequency of the first mode was obtained by CoventorWare software and it was found to be 18.552 kHz compared to its modelled value of 17.211 kHz, within an error of 7.2 %. Maximum displacement of 8.35 µm and capacitance of 29.57 fF were obtained when the device was driven by applying 15 mA current and 50 mT magnetic field.

  17. 牛病毒性腹泻病毒弱毒活疫苗免疫持续期的研究%The Efficacy of the Live Attenuated Bovine Viral Diarrhea Virus SM Vaccine Strain

    Institute of Scientific and Technical Information of China (English)

    张淑琴; 郭利; 王伟; 张亭亭; 吴永旺; 武华

    2012-01-01

    The study was designed to evalutate neutralizing(SN) antibodies against bovine viral diarrhea virus(BVDV) in the calves vaccinated with the live attenuated bovine viral diarrhea virus SM vaccine.A total of 30 healthy calves at weaning were randomly divided into two groups,with 15 calves in vaccinate group and 15 in control group.The attenuated BVDV SM vaccine strain was administrated via intramuscular injection on the neck at a single dose and challenged with a virulent BVDV-JL virus by nasal spray.The blood sample were collected at different time points for monitoring SN antibody titers.The results indicated that the SN antibody titers in the vaccinated calves maintained at a relative high level until 12 month post-vaccination,and the vaccinated calves were effectively protected from the challenge,as detected by the white blood cell count(WBC) and,virus shedding.therefore,the duration of immunity of the vaccine was at lease for 9 months.%为检测牛病毒性腹泻病毒(BVDV)弱毒活疫苗在免疫牛体内抗体产生及其消长规律,评价弱毒疫苗的保护效力,并确定免疫持续期,本试验对免疫试验牛每头颈部肌肉接种BVDV SM株弱毒疫苗104.5TCID50,监测血清抗体效价,进行免疫持续期的确定。在疫苗免疫后的6个月、9个月和12个月,分别抽取5头免疫组和5头对照组牛,采用BVDV-JL强毒株进行攻毒试验,每头牛攻毒剂量为6×107.0TCID50/mL。结果显示疫苗免疫后12个月时血清中和抗体效价仍维持在1∶1048以上。攻毒结果显示,在3个不同时间点进行强毒攻击后,免疫组所有动物白细胞数量都没有下降也没有分离到病毒,而对照组动物白细胞数下降均超过30%,6个月和9个月时动物血清中均能分离到病毒,而12个月对照组动物由于年龄大,没有分离到病毒,因此暂定此疫苗的免疫持续期为9个月。

  18. 牛病毒性腹泻弱毒活疫苗免疫持续期的研究%The Efficacy of the Live Attenuated Bovine Viral Diarrhea Virus SM Vaccine Strain

    Institute of Scientific and Technical Information of China (English)

    张淑琴; 郭利; 王炜; 张亭亭; 吴永旺; 武华

    2012-01-01

    The study was designed to evaluate neutralizing (SN) antibodies against bovine viral diarrhea virus (BVDV) in the calves vaccinated with the live attenuated bovine viral diarrhea virus SM vaccine. A total of 30 healthy calves at weaning were randomly divided into two groups, with 15 calves in vaccinate group and 15 in control group. The attenuated BVDV SM vaccine strain was administrated via intramuscular injection on the neck at a single dose and challenged with a virulent BVDV-JL virus by nasal spray. The blood samples were collected at different time points for monitoring SN antibody titers. The results indicated that the SN antibody titers in the vaccinated calves maintained at a relative high level until 12 month post-vaccination, and the vaccinated calves were effectively protected from the challenge, as detected by the white blood cell count (WBC) and virus shedding. Therefore, the duration of immunity of the vaccine was at lease for 9 months.%为检测牛病毒性腹泻病毒(BVDV)弱毒活疫苗在免疫牛体内抗体产生及其消长规律,评价弱毒疫苗的保护效力,并确定免疫持续期,本试验对免疫试验牛每头颈部肌肉接种BVDV SM株弱毒疫苗104.5TCID50/头,监测血清抗体效价,进行免疫持续期的确定.在疫苗免疫后的6、9和12个月分别抽取5头免疫组和5头对照组牛采用BVDV-JL强毒株进行攻毒试验,每头牛攻毒剂量为6×107.0 TCID50/mL.结果显示疫苗免疫后12个月时血清中和抗体效价仍维持在1∶1048以上,攻毒结果显示3个时间点强毒攻击后,免疫组所有动物白细胞数量都没有下降也没有分离到病毒,而对照组动物白细胞数下降均超过30%,6和9个月动物均分离到病毒,而12个月对照组动物由于年龄大,没有分离到病毒,因此暂定此疫苗的免疫持续期为9个月.

  19. Missed Opportunities for Measles, Mumps, and Rubella (MMR Immunization in Mesoamerica: Potential Impact on Coverage and Days at Risk.

    Directory of Open Access Journals (Sweden)

    Ali H Mokdad

    Full Text Available Recent outbreaks of measles in the Americas have received news and popular attention, noting the importance of vaccination to population health. To estimate the potential increase in immunization coverage and reduction in days at risk if every opportunity to vaccinate a child was used, we analyzed vaccination histories of children 11-59 months of age from large household surveys in Mesoamerica.Our study included 22,234 children aged less than 59 months in El Salvador, Guatemala, Honduras, Mexico, Nicaragua, and Panama. Child vaccination cards were used to calculate coverage of measles, mumps, and rubella (MMR and to compute the number of days lived at risk. A child had a missed opportunity for vaccination if their card indicated a visit for vaccinations at which the child was not caught up to schedule for MMR. A Cox proportional hazards model was used to compute the hazard ratio associated with the reduction in days at risk, accounting for missed opportunities.El Salvador had the highest proportion of children with a vaccine card (91.2% while Nicaragua had the lowest (76.5%. Card MMR coverage ranged from 44.6% in Mexico to 79.6% in Honduras while potential coverage accounting for missed opportunities ranged from 70.8% in Nicaragua to 96.4% in El Salvador. Younger children were less likely to have a missed opportunity. In Panama, children from households with higher expenditure were more likely to have a missed opportunity for MMR vaccination compared to the poorest (OR 1.62, 95% CI: 1.06-2.47. In Nicaragua, compared to children of mothers with no education, children of mothers with primary education and secondary education were less likely to have a missed opportunity (OR 0.46, 95% CI: 0.24-0.88 and OR 0.25, 95% CI: 0.096-0.65, respectively. Mean days at risk for MMR ranged from 158 in Panama to 483 in Mexico while potential days at risk ranged from 92 in Panama to 239 in El Salvador.Our study found high levels of missed opportunities for

  20. Missed Opportunities for Measles, Mumps, and Rubella (MMR) Immunization in Mesoamerica: Potential Impact on Coverage and Days at Risk.

    Science.gov (United States)

    Mokdad, Ali H; Gagnier, Marielle C; Colson, K Ellicott; Dansereau, Emily; Zúñiga-Brenes, Paola; Ríos-Zertuche, Diego; Haakenstad, Annie; Johanns, Casey K; Palmisano, Erin B; Hernandez, Bernardo; Iriarte, Emma

    2015-01-01

    Recent outbreaks of measles in the Americas have received news and popular attention, noting the importance of vaccination to population health. To estimate the potential increase in immunization coverage and reduction in days at risk if every opportunity to vaccinate a child was used, we analyzed vaccination histories of children 11-59 months of age from large household surveys in Mesoamerica. Our study included 22,234 children aged less than 59 months in El Salvador, Guatemala, Honduras, Mexico, Nicaragua, and Panama. Child vaccination cards were used to calculate coverage of measles, mumps, and rubella (MMR) and to compute the number of days lived at risk. A child had a missed opportunity for vaccination if their card indicated a visit for vaccinations at which the child was not caught up to schedule for MMR. A Cox proportional hazards model was used to compute the hazard ratio associated with the reduction in days at risk, accounting for missed opportunities. El Salvador had the highest proportion of children with a vaccine card (91.2%) while Nicaragua had the lowest (76.5%). Card MMR coverage ranged from 44.6% in Mexico to 79.6% in Honduras while potential coverage accounting for missed opportunities ranged from 70.8% in Nicaragua to 96.4% in El Salvador. Younger children were less likely to have a missed opportunity. In Panama, children from households with higher expenditure were more likely to have a missed opportunity for MMR vaccination compared to the poorest (OR 1.62, 95% CI: 1.06-2.47). In Nicaragua, compared to children of mothers with no education, children of mothers with primary education and secondary education were less likely to have a missed opportunity (OR 0.46, 95% CI: 0.24-0.88 and OR 0.25, 95% CI: 0.096-0.65, respectively). Mean days at risk for MMR ranged from 158 in Panama to 483 in Mexico while potential days at risk ranged from 92 in Panama to 239 in El Salvador. Our study found high levels of missed opportunities for immunizing

  1. Measles, mumps, rubella, and varicella seroprevalence in refugees in Germany in 2015.

    Science.gov (United States)

    Jablonka, Alexandra; Happle, Christine; Grote, Ulrike; Schleenvoigt, Benjamin Thomas; Hampel, Annika; Dopfer, Christian; Hansen, Gesine; Schmidt, Reinhold Ernst; Behrens, Georg M N

    2016-12-01

    The current extent of migration poses emerging socio-economic and humanitarian challenges. Little is known on vaccination rates in migrants entering Europe, and the implementation of guidelines for serological testing and vaccination of refugees are pending. We conducted seroprevalence analyses for measles, mumps, rubella and varicella (MMRV) in 678 refugees coming to Germany during the current crisis. The mean age of refugees was 28.8±11.4 years, and 76.1 % of subjects were male. Overall, IgG seronegativity was 7.4 % (95 % CI 5.5-9.6) for measles, 10.2 % (95 % CI 8.0-12.5) for mumps, 2.2 % (95 % CI 1.2-3.4) for rubella, and 3.3 % (95 % CI 1.9-4.9) for varicella. Seropositivity rates were age-dependent with considerably low values in children. For example, overall MMR immunity was 90.9 % (95 % CI 88.8-93.1), but only 73.1 % of minor aged refugees displayed complete seroprevalence against all three diseases, and only 68.9 % of children and adolescents were completely MMRV immune. Our initial data set suggests overall satisfactory MMRV immunity in adult migrants coming to Europe, but the observed low MMRV seroprevalences in refugee children support thorough and prompt vaccination of young migrants entering Europe. Taken together, our data set underlines the urgent need to implement and validate vaccination guidelines for refugee care in the current crisis.

  2. 湖北省农村地区2010年麻疹疫苗强化免疫结果分析%Evaluation on the supplementary immunization activity (SIAS)of the attenuated live measles vaccine (MV)

    Institute of Scientific and Technical Information of China (English)

    王迎; 许智; 谭晓东; 叶建君; 张迟; 赵明江; 占发先

    2012-01-01

    Objective To evaluate the implementation of the supplementary immunization activities (SIAS) of the attenuated live measles vaccine (MV) in Hubei's rural district in 2010. Methods Four hundred and seventy four children between 8 months and 4 yean old were selected with multi-stage stratified cluster sampling in rural area of Hubei. The self-designed questionnaire about MV SIAS was used for field visit and questionnaire survey. SPSS 17.0 was applied for data a-nalysis. Results The immunization coverage rate was 96. 6% , the supplementary inoculation rate after massive immunization stage was 50. 0%. The satisfaction rate of the parents for service attitude, environment and organization were 97. 2% , 96.7% and 97. 8% respectively. Three children had never received any measles vaccination,accounting for 6%o. Conclusion The immunization coverage rate was 95% , reaching the expected target. Further effort is needed to increase the supplementary inoculation rate. Those children never received measles vaccination should be the priority population for the elimination of measles.%目的 评估湖北省2010年麻疹疫苗强化免疫在农村实施的情况.方法 采用多阶段分层整群随机抽样方法抽取湖北省6个郊区(县)8月龄~4岁儿童共474人,采用自编的调查表,以现况调查的方式进行入户问卷调查.结果 本次调查麻疹疫苗强化免疫接种率为96.6%,集中接种后,补种率为50%;家长对于接种时医务人员的服务态度、接种点环境、接种组织情况满意者分别为97.2%、96.7%、97.8%;麻疹疫苗接种零剂次者3人,占调查样本的6‰.结论 湖北省农村地区2010年麻疹疫苗强化免疫接种率达到了95%的目标.

  3. Incidence of live-attenuated influenza vaccine administration beyond expiry date in children and adolescents aged 2-17 years in the UK: a population-based cohort study.

    Science.gov (United States)

    Caspard, Herve; Wise, Robert P; Steffey, Amy; Brody, Robert S

    2017-07-17

    To estimate the proportion of live-attenuated influenza vaccine (LAIV) doses administered beyond expiry date in children and adolescents during influenza seasons 2013-2014 and 2014-2015 in the UK. This was a retrospective cohort study. Two cohorts of children and adolescents who received LAIV from 1 September 2013 to 31 March 2014 and from 1 September 2014 to 31 March 2015 and aged 2-17 years at time of LAIV administration were identified from the Clinical Practice Research Datalink (CPRD). More than 500 primary care practices in the UK. Proportions of vaccine doses administered beyond expiry date were assessed among 47 396 and 67 099 LAIV recipients with a documented vaccine lot identifier in influenza seasons 2013-2014 and 2014-2015, respectively. None. Administrations of expired LAIV were ascertained by comparison of vaccination dates in CPRD records with expiration dates in AstraZeneca/MedImmune lot distribution data. Overall, 245 LAIV recipients, 80 in 2013-2014 and 165 in 2014-2015, received a dose after its expiration date, yielding proportion estimates of 1.7 per 1000 doses (95% CI 1.3 to 2.1) in season 2013-2014 and 2.5 per 1000 (95% CI 2.1 to 2.8) in season 2014-2015. This proportion increased above 1.0% after December during each season. Most (84% in influenza season 2013-2014 and 59% in influenza season 2014-2015) received an expired dose expiration date. The proportion was higher in London (relative risk 1.93 (95% CI 1.25 to 2.99)) and when the number of LAIV recipients registered in the practice was lower than the median number per practice (relative risk 2.69 (95% CI 1.99 to 3.62)). Administration of expired LAIV doses occurs infrequently. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  4. Mumps Photos

    Science.gov (United States)

    ... tubercles. Additional Images and Regulations American Academy of Pediatrics Immunization Action Coalition Public Health Image Library (PHIL) Top of Page Related Links World Health Organization Medline Plus Language: English Español (Spanish) File Formats Help: How do I view different ...

  5. Search for the lepton-flavour violating decays $B^0_{(s)} \\rightarrow e^\\pm \\mu^\\mp$

    CERN Document Server

    Aaij, Roel; LHCb Collaboration; Adinolfi, Marco; Ajaltouni, Ziad; Akar, Simon; Albrecht, Johannes; Alessio, Federico; Alexander, Michael; Alfonso Albero, Alejandro; Ali, Suvayu; Alkhazov, Georgy; Alvarez Cartelle, Paula; Alves Jr, Antonio Augusto; Amato, Sandra; Amerio, Silvia; Amhis, Yasmine; An, Liupan; Anderlini, Lucio; Andreassi, Guido; Andreotti, Mirco; Andrews, Jason; Appleby, Robert; Archilli, Flavio; d'Argent, Philippe; Arnau Romeu, Joan; Artamonov, Alexander; Artuso, Marina; Aslanides, Elie; Atzeni, Michele; Auriemma, Giulio; Baalouch, Marouen; Babuschkin, Igor; Bachmann, Sebastian; Back, John; Badalov, Alexey; Baesso, Clarissa; Baker, Sophie; Balagura, Vladislav; Baldini, Wander; Baranov, Alexander; Barlow, Roger; Barschel, Colin; Barsuk, Sergey; Barter, William; Baryshnikov, Fedor; Batozskaya, Varvara; Battista, Vincenzo; Bay, Aurelio; Beaucourt, Leo; Beddow, John; Bedeschi, Franco; Bediaga, Ignacio; Beiter, Andrew; Bel, Lennaert; Beliy, Nikita; Bellee, Violaine; Belloli, Nicoletta; Belous, Konstantin; Belyaev, Ivan; Ben-Haim, Eli; Bencivenni, Giovanni; Benson, Sean; Beranek, Sarah; Berezhnoy, Alexander; Bernet, Roland; Berninghoff, Daniel; Bertholet, Emilie; Bertolin, Alessandro; Betancourt, Christopher; Betti, Federico; Bettler, Marc-Olivier; van Beuzekom, Martinus; Bezshyiko, Iaroslava; Bifani, Simone; Billoir, Pierre; Birnkraut, Alex; Bizzeti, Andrea; Bjørn, Mikkel; Blake, Thomas; Blanc, Frederic; Blusk, Steven; Bocci, Valerio; Boettcher, Thomas; Bondar, Alexander; Bondar, Nikolay; Bordyuzhin, Igor; Borgheresi, Alessio; Borghi, Silvia; Borisyak, Maxim; Borsato, Martino; Bossu, Francesco; Boubdir, Meriem; Bowcock, Themistocles; Bowen, Espen Eie; Bozzi, Concezio; Braun, Svende; Britton, Thomas; Brodzicka, Jolanta; Brundu, Davide; Buchanan, Emma; Burr, Christopher; Bursche, Albert; Buytaert, Jan; Byczynski, Wiktor; Cadeddu, Sandro; Cai, Hao; Calabrese, Roberto; Calladine, Ryan; Calvi, Marta; Calvo Gomez, Miriam; Camboni, Alessandro; Campana, Pierluigi; Campora Perez, Daniel Hugo; Capriotti, Lorenzo; Carbone, Angelo; Carboni, Giovanni; Cardinale, Roberta; Cardini, Alessandro; Carniti, Paolo; Carson, Laurence; Carvalho Akiba, Kazuyoshi; Casse, Gianluigi; Cassina, Lorenzo; Cattaneo, Marco; Cavallero, Giovanni; Cenci, Riccardo; Chamont, David; Chapman, Matthew George; Charles, Matthew; Charpentier, Philippe; Chatzikonstantinidis, Georgios; Chefdeville, Maximilien; Chen, Shanzhen; Cheung, Shu Faye; Chitic, Stefan-Gabriel; Chobanova, Veronika; Chrzaszcz, Marcin; Chubykin, Alexsei; Ciambrone, Paolo; Cid Vidal, Xabier; Ciezarek, Gregory; Clarke, Peter; Clemencic, Marco; Cliff, Harry; Closier, Joel; Cogan, Julien; Cogneras, Eric; Cogoni, Violetta; Cojocariu, Lucian; Collins, Paula; Colombo, Tommaso; Comerma-Montells, Albert; Contu, Andrea; Cook, Andrew; Coombs, George; Coquereau, Samuel; Corti, Gloria; Corvo, Marco; Costa Sobral, Cayo Mar; Couturier, Benjamin; Cowan, Greig; Craik, Daniel Charles; Crocombe, Andrew; Cruz Torres, Melissa Maria; Currie, Robert; D'Ambrosio, Carmelo; Da Cunha Marinho, Franciole; Dall'Occo, Elena; Dalseno, Jeremy; Davis, Adam; De Aguiar Francisco, Oscar; De Capua, Stefano; De Cian, Michel; De Miranda, Jussara; De Paula, Leandro; De Serio, Marilisa; De Simone, Patrizia; Dean, Cameron Thomas; Decamp, Daniel; Del Buono, Luigi; Dembinski, Hans Peter; Demmer, Moritz; Dendek, Adam; Derkach, Denis; Deschamps, Olivier; Dettori, Francesco; Dey, Biplab; Di Canto, Angelo; Di Nezza, Pasquale; Dijkstra, Hans; Dordei, Francesca; Dorigo, Mirco; Dosil Suárez, Alvaro; Douglas, Lauren; Dovbnya, Anatoliy; Dreimanis, Karlis; Dufour, Laurent; Dujany, Giulio; Durante, Paolo; Dzhelyadin, Rustem; Dziewiecki, Michal; Dziurda, Agnieszka; Dzyuba, Alexey; Easo, Sajan; Ebert, Marcus; Egede, Ulrik; Egorychev, Victor; Eidelman, Semen; Eisenhardt, Stephan; Eitschberger, Ulrich; Ekelhof, Robert; Eklund, Lars; Ely, Scott; Esen, Sevda; Evans, Hannah Mary; Evans, Timothy; Falabella, Antonio; Farley, Nathanael; Farry, Stephen; Fazzini, Davide; Federici, Luca; Ferguson, Dianne; Fernandez, Gerard; Fernandez Declara, Placido; Fernandez Prieto, Antonio; Ferrari, Fabio; Ferreira Rodrigues, Fernando; Ferro-Luzzi, Massimiliano; Filippov, Sergey; Fini, Rosa Anna; Fiorini, Massimiliano; Firlej, Miroslaw; Fitzpatrick, Conor; Fiutowski, Tomasz; Fleuret, Frederic; Fohl, Klaus; Fontana, Marianna; Fontanelli, Flavio; Forshaw, Dean Charles; Forty, Roger; Franco Lima, Vinicius; Frank, Markus; Frei, Christoph; Fu, Jinlin; Funk, Wolfgang; Furfaro, Emiliano; Färber, Christian; Gabriel, Emmy; Gallas Torreira, Abraham; Galli, Domenico; Gallorini, Stefano; Gambetta, Silvia; Gandelman, Miriam; Gandini, Paolo; Gao, Yuanning; Garcia Martin, Luis Miguel; García Pardiñas, Julián; Garra Tico, Jordi; Garrido, Lluis; Garsed, Philip John; Gascon, David; Gaspar, Clara; Gavardi, Laura; Gazzoni, Giulio; Gerick, David; Gersabeck, Evelina; Gersabeck, Marco; Gershon, Timothy; Ghez, Philippe; Gianì, Sebastiana; Gibson, Valerie; Girard, Olivier Göran; Giubega, Lavinia-Helena; Gizdov, Konstantin; Gligorov, Vladimir; Golubkov, Dmitry; Golutvin, Andrey; Gomes, Alvaro; Gorelov, Igor Vladimirovich; Gotti, Claudio; Govorkova, Ekaterina; Grabowski, Jascha Peter; Graciani Diaz, Ricardo; Granado Cardoso, Luis Alberto; Graugés, Eugeni; Graverini, Elena; Graziani, Giacomo; Grecu, Alexandru; Greim, Roman; Griffith, Peter; Grillo, Lucia; Gruber, Lukas; Gruberg Cazon, Barak Raimond; Grünberg, Oliver; Gushchin, Evgeny; Guz, Yury; Gys, Thierry; Göbel, Carla; Hadavizadeh, Thomas; Hadjivasiliou, Christos; Haefeli, Guido; Haen, Christophe; Haines, Susan; Hamilton, Brian; Han, Xiaoxue; Hancock, Thomas Henry; Hansmann-Menzemer, Stephanie; Harnew, Neville; Harnew, Samuel; Hasse, Christoph; Hatch, Mark; He, Jibo; Hecker, Malte; Heinicke, Kevin; Heister, Arno; Hennessy, Karol; Henrard, Pierre; Henry, Louis; van Herwijnen, Eric; Heß, Miriam; Hicheur, Adlène; Hill, Donal; Hombach, Christoph; Hopchev, Plamen Hristov; Hu, Wenhua; Huard, Zachary; Hulsbergen, Wouter; Humair, Thibaud; Hushchyn, Mikhail; Hutchcroft, David; Ibis, Philipp; Idzik, Marek; Ilten, Philip; Jacobsson, Richard; Jalocha, Pawel; Jans, Eddy; Jawahery, Abolhassan; Jiang, Feng; John, Malcolm; Johnson, Daniel; Jones, Christopher; Joram, Christian; Jost, Beat; Jurik, Nathan; Kandybei, Sergii; Karacson, Matthias; Kariuki, James Mwangi; Karodia, Sarah; Kazeev, Nikita; Kecke, Matthieu; Keizer, Floris; Kelsey, Matthew; Kenzie, Matthew; Ketel, Tjeerd; Khairullin, Egor; Khanji, Basem; Khurewathanakul, Chitsanu; Kirn, Thomas; Klaver, Suzanne; Klimaszewski, Konrad; Klimkovich, Tatsiana; Koliiev, Serhii; Kolpin, Michael; Komarov, Ilya; Kopecna, Renata; Koppenburg, Patrick; Kosmyntseva, Alena; Kotriakhova, Sofia; Kozeiha, Mohamad; Kravchuk, Leonid; Kreps, Michal; Kress, Felix Johannes; Krokovny, Pavel; Kruse, Florian; Krzemien, Wojciech; Kucewicz, Wojciech; Kucharczyk, Marcin; Kudryavtsev, Vasily; Kuonen, Axel Kevin; Kvaratskheliya, Tengiz; Lacarrere, Daniel; Lafferty, George; Lai, Adriano; Lanfranchi, Gaia; Langenbruch, Christoph; Latham, Thomas; Lazzeroni, Cristina; Le Gac, Renaud; Leflat, Alexander; Lefrançois, Jacques; Lefèvre, Regis; Lemaitre, Florian; Lemos Cid, Edgar; Leroy, Olivier; Lesiak, Tadeusz; Leverington, Blake; Li, Pei-Rong; Li, Tenglin; Li, Yiming; Li, Zhuoming; Likhomanenko, Tatiana; Lindner, Rolf; Lionetto, Federica; Lisovskyi, Vitalii; Liu, Xuesong; Loh, David; Loi, Angelo; Longstaff, Iain; Lopes, Jose; Lucchesi, Donatella; Lucio Martinez, Miriam; Luo, Haofei; Lupato, Anna; Luppi, Eleonora; Lupton, Oliver; Lusiani, Alberto; Lyu, Xiao-Rui; Machefert, Frederic; Maciuc, Florin; Macko, Vladimir; Mackowiak, Patrick; Maddrell-Mander, Samuel; Maev, Oleg; Maguire, Kevin; Maisuzenko, Dmitrii; Majewski, Maciej Witold; Malde, Sneha; Malecki, Bartosz; Malinin, Alexander; Maltsev, Timofei; Manca, Giulia; Mancinelli, Giampiero; Marangotto, Daniele; Maratas, Jan; Marchand, Jean François; Marconi, Umberto; Marin Benito, Carla; Marinangeli, Matthieu; Marino, Pietro; Marks, Jörg; Martellotti, Giuseppe; Martin, Morgan; Martinelli, Maurizio; Martinez Santos, Diego; Martinez Vidal, Fernando; Martins Tostes, Danielle; Massacrier, Laure Marie; Massafferri, André; Matev, Rosen; Mathad, Abhijit; Mathe, Zoltan; Matteuzzi, Clara; Mauri, Andrea; Maurice, Emilie; Maurin, Brice; Mazurov, Alexander; McCann, Michael; McNab, Andrew; McNulty, Ronan; Mead, James Vincent; Meadows, Brian; Meaux, Cedric; Meier, Frank; Meinert, Nis; Melnychuk, Dmytro; Merk, Marcel; Merli, Andrea; Michielin, Emanuele; Milanes, Diego Alejandro; Millard, Edward James; Minard, Marie-Noelle; Minzoni, Luca; Mitzel, Dominik Stefan; Mogini, Andrea; Molina Rodriguez, Josue; Mombächer, Titus; Monroy, Igancio Alberto; Monteil, Stephane; Morandin, Mauro; Morello, Michael Joseph; Morgunova, Olga; Moron, Jakub; Morris, Adam Benjamin; Mountain, Raymond; Muheim, Franz; Mulder, Mick; Müller, Dominik; Müller, Janine; Müller, Katharina; Müller, Vanessa; Naik, Paras; Nakada, Tatsuya; Nandakumar, Raja; Nandi, Anita; Nasteva, Irina; Needham, Matthew; Neri, Nicola; Neubert, Sebastian; Neufeld, Niko; Neuner, Max; Nguyen, Thi Dung; Nguyen-Mau, Chung; Nieswand, Simon; Niet, Ramon; Nikitin, Nikolay; Nikodem, Thomas; Nogay, Alla; O'Hanlon, Daniel Patrick; Oblakowska-Mucha, Agnieszka; Obraztsov, Vladimir; Ogilvy, Stephen; Oldeman, Rudolf; Onderwater, Gerco; Ossowska, Anna; Otalora Goicochea, Juan Martin; Owen, Patrick; Oyanguren, Maria Aranzazu; Pais, Preema Rennee; Palano, Antimo; Palutan, Matteo; Papanestis, Antonios; Pappagallo, Marco; Pappalardo, Luciano; Parker, William; Parkes, Christopher; Passaleva, Giovanni; Pastore, Alessandra; Patel, Mitesh; Patrignani, Claudia; Pearce, Alex; Pellegrino, Antonio; Penso, Gianni; Pepe Altarelli, Monica; Perazzini, Stefano; Perret, Pascal; Pescatore, Luca; Petridis, Konstantinos; Petrolini, Alessandro; Petrov, Aleksandr; Petruzzo, Marco; Picatoste Olloqui, Eduardo; Pietrzyk, Boleslaw; Pikies, Malgorzata; Pinci, Davide; Pisani, Flavio; Pistone, Alessandro; Piucci, Alessio; Placinta, Vlad-Mihai; Playfer, Stephen; Plo Casasus, Maximo; Polci, Francesco; Poli Lener, Marco; Poluektov, Anton; Polyakov, Ivan; Polycarpo, Erica; Pomery, Gabriela Johanna; Ponce, Sebastien; Popov, Alexander; Popov, Dmitry; Poslavskii, Stanislav; Potterat, Cédric; Price, Eugenia; Prisciandaro, Jessica; Prouve, Claire; Pugatch, Valery; Puig Navarro, Albert; Pullen, Hannah Louise; Punzi, Giovanni; Qian, Wenbin; Quagliani, Renato; Quintana, Boris; Rachwal, Bartlomiej; Rademacker, Jonas; Rama, Matteo; Ramos Pernas, Miguel; Rangel, Murilo; Raniuk, Iurii; Ratnikov, Fedor; Raven, Gerhard; Ravonel Salzgeber, Melody; Reboud, Meril; Redi, Federico; Reichert, Stefanie; dos Reis, Alberto; Remon Alepuz, Clara; Renaudin, Victor; Ricciardi, Stefania; Richards, Sophie; Rihl, Mariana; Rinnert, Kurt; Rives Molina, Vicente; Robbe, Patrick; Robert, Arnaud; Rodrigues, Ana Barbara; Rodrigues, Eduardo; Rodriguez Lopez, Jairo Alexis; Rogozhnikov, Alexey; Roiser, Stefan; Rollings, Alexandra Paige; Romanovskiy, Vladimir; Romero Vidal, Antonio; Ronayne, John William; Rotondo, Marcello; Rudolph, Matthew Scott; Ruf, Thomas; Ruiz Valls, Pablo; Ruiz Vidal, Joan; Saborido Silva, Juan Jose; Sadykhov, Elnur; Sagidova, Naylya; Saitta, Biagio; Salustino Guimaraes, Valdir; Sanchez Mayordomo, Carlos; Sanmartin Sedes, Brais; Santacesaria, Roberta; Santamarina Rios, Cibran; Santimaria, Marco; Santovetti, Emanuele; Sarpis, Gediminas; Sarti, Alessio; Satriano, Celestina; Satta, Alessia; Saunders, Daniel Martin; Savrina, Darya; Schael, Stefan; Schellenberg, Margarete; Schiller, Manuel; Schindler, Heinrich; Schmelling, Michael; Schmelzer, Timon; Schmidt, Burkhard; Schneider, Olivier; Schopper, Andreas; Schreiner, HF; Schubiger, Maxime; Schune, Marie Helene; Schwemmer, Rainer; Sciascia, Barbara; Sciubba, Adalberto; Semennikov, Alexander; Sepulveda, Eduardo Enrique; Sergi, Antonino; Serra, Nicola; Serrano, Justine; Sestini, Lorenzo; Seyfert, Paul; Shapkin, Mikhail; Shapoval, Illya; Shcheglov, Yury; Shears, Tara; Shekhtman, Lev; Shevchenko, Vladimir; Siddi, Benedetto Gianluca; Silva Coutinho, Rafael; Silva de Oliveira, Luiz Gustavo; Simi, Gabriele; Simone, Saverio; Sirendi, Marek; Skidmore, Nicola; Skwarnicki, Tomasz; Smith, Eluned; Smith, Iwan Thomas; Smith, Jackson; Smith, Mark; Soares Lavra, Lais; Sokoloff, Michael; Soler, Paul; Souza De Paula, Bruno; Spaan, Bernhard; Spradlin, Patrick; Sridharan, Srikanth; Stagni, Federico; Stahl, Marian; Stahl, Sascha; Stefko, Pavol; Stefkova, Slavomira; Steinkamp, Olaf; Stemmle, Simon; Stenyakin, Oleg; Stepanova, Margarita; Stevens, Holger; Stone, Sheldon; Storaci, Barbara; Stracka, Simone; Stramaglia, Maria Elena; Straticiuc, Mihai; Straumann, Ulrich; Sun, Jiayin; Sun, Liang; Sutcliffe, William; Swientek, Krzysztof; Syropoulos, Vasileios; Szumlak, Tomasz; Szymanski, Maciej Pawel; T'Jampens, Stephane; Tayduganov, Andrey; Tekampe, Tobias; Tellarini, Giulia; Teubert, Frederic; Thomas, Eric; van Tilburg, Jeroen; Tilley, Matthew James; Tisserand, Vincent; Tobin, Mark; Tolk, Siim; Tomassetti, Luca; Tonelli, Diego; Toriello, Francis; Tourinho Jadallah Aoude, Rafael; Tournefier, Edwige; Traill, Murdo; Tran, Minh Tâm; Tresch, Marco; Trisovic, Ana; Tsaregorodtsev, Andrei; Tsopelas, Panagiotis; Tully, Alison; Tuning, Niels; Ukleja, Artur; Usachov, Andrii; Ustyuzhanin, Andrey; Uwer, Ulrich; Vacca, Claudia; Vagner, Alexander; Vagnoni, Vincenzo; Valassi, Andrea; Valat, Sebastien; Valenti, Giovanni; Vazquez Gomez, Ricardo; Vazquez Regueiro, Pablo; Vecchi, Stefania; van Veghel, Maarten; Velthuis, Jaap; Veltri, Michele; Veneziano, Giovanni; Venkateswaran, Aravindhan; Verlage, Tobias Anton; Vernet, Maxime; Vesterinen, Mika; Viana Barbosa, Joao Vitor; Viaud, Benoit; Vieira, Daniel; Vieites Diaz, Maria; Viemann, Harald; Vilasis-Cardona, Xavier; Vitti, Marcela; Volkov, Vladimir; Vollhardt, Achim; Voneki, Balazs; Vorobyev, Alexey; Vorobyev, Vitaly; Voß, Christian; de Vries, Jacco; Vázquez Sierra, Carlos; Waldi, Roland; Wallace, Charlotte; Wallace, Ronan; Walsh, John; Wang, Jianchun; Ward, David; Wark, Heather Mckenzie; Watson, Nigel; Websdale, David; Weiden, Andreas; Weisser, Constantin; Whitehead, Mark; Wicht, Jean; Wilkinson, Guy; Wilkinson, Michael; Williams, Mark Richard James; Williams, Matthew; Williams, Mike; Williams, Timothy; Wilson, Fergus; Wimberley, Jack; Winn, Michael Andreas; Wishahi, Julian; Wislicki, Wojciech; Witek, Mariusz; Wormser, Guy; Wotton, Stephen; Wraight, Kenneth; Wyllie, Kenneth; Xie, Yuehong; Xu, Menglin; Xu, Zhirui; Yang, Zhenwei; Yang, Zishuo; Yao, Yuezhe; Yin, Hang; Yu, Jiesheng; Yuan, Xuhao; Yushchenko, Oleg; Zarebski, Kristian Alexander; Zavertyaev, Mikhail; Zhang, Liming; Zhang, Yanxi; Zhelezov, Alexey; Zheng, Yangheng; Zhu, Xianglei; Zhukov, Valery; Zonneveld, Jennifer Brigitta; Zucchelli, Stefano

    2017-01-01

    A search for the lepton-flavour violating decays $B^0_s \\rightarrow e^\\pm \\mu^\\mp$ and $B^0 \\rightarrow e^\\pm \\mu^\\mp$ is performed based on a sample of proton-proton collision data corresponding to an integrated luminosity of 3 $\\mbox{fb}^{-1}$, collected with the LHCb experiment at centre-of-mass energies of $7$ and $8 ~ \\text {TeV}$. The observed yields are consistent with the background-only hypothesis. Upper limits on the branching fractions are determined to be ${\\mathcal {B} (B^0_s \\rightarrow e^\\pm \\mu^ \\mp) < 5.4 ~(6.3) \\times 10^{-9}}$ and $\\mathcal {B} (B^0 \\rightarrow e^\\pm \\mu^ \\mp) < 1.0 ~(1.3) \\times 10^{-9}$ at $90\\%~ (95\\%)$ confidence level, which are the strongest limits on these decays to date.

  6. 云南省麻疹减毒活疫苗补充免疫活动效果评价%Effect Evaluation on Supplementary Immunization Activities of Measles Attenuated Live Vaccine in Yunnan Province

    Institute of Scientific and Technical Information of China (English)

    余文; 黄国斐; 罗梅; 李立群; 张杰; 李徽; 丁峥嵘

    2013-01-01

    Objective To evaluate the effect of supplementary immunization activities (SIA)of measles attenuated live vaccine (MV).Methods Collecting immunization data of SIA,field investigation,the population antibody level and data from notifiable diseases reporting system.Analyzing the data with descriptire epidemiology.Result The coverage of SIA of Measles vaccine was 97.90% and 98.10% during 2009-2011 respectively.The coverage rate are > 85% in 90% township by fast evaluation.The population antibody level was 87.22% and 95.03%.Before MV SIA(Jan.-Oct.2008),the measles incidence was 2850 cases,with an incidence rate of 6.314/100,000.After MV SIA,the measles incidence was reduced to 638 cases and the incidence rate to 1.404/100,000 in the same period in 2009 and to 86 cases with the incidence of 0.187/100,000 in 2010.By the end of 2010,the reported measles incidence and incidence rate reduced to the lowest level in the history.ConcIusion The effectiveness of MV SIA was good in Yunnan province in the year of 2008 and 2010.On the basis of routine immunization,MV SIA can rapidly improve herd immunity and effectively block the dissemination of measles virus.For realizing the goal of Measles elimination,it is necessary to improve and maintain the coverage of routine immunization and SIAs,strengthen surveillance and management,conduct evaluation and supervision.%目的 评估云南省2008年和2010年麻疹减毒活疫苗(Measles Attenuated Live Vaccine,MV)补充免疫活动(Supplementary Immunization Activities,SIA)控制麻疹的效果.方法 收集云南省2008年、2010年MV SIA接种、现场调查、人群抗体水平及法定传染病报告系统的麻疹疫情资料,应用描述流行病学方法评价控制效果.结果 2008年和2010年,MV SIA报告接种率分别为97.90%和98.21%;报告>90%的乡(镇)快速评估接种率>85%;人群麻疹抗体监测阳性率分别为87.22%和95.03%.MV SIA前,即2008年1~10月,麻疹报告发病2850

  7. THE INFLUENCE OF DOUBLE IMMUNIZATION ON MORBIDITY OF MEASLES, MUMPS AND RUBELLA IN THE NORTH-WEST REGION OF RUSSIA

    Directory of Open Access Journals (Sweden)

    L. V. Lyalina

    2012-01-01

    Full Text Available Abstract. The influence of double immunization on measles, mumps and rubella incidence in the North-West Federal District (North-West Russia has been analyzed. Due to the vaccination of the population morbidity of these infections in the region has decreased significantly. The necessity to improve the surveillance system due to changes in the manifestations of the epidemic process particularly connected with increasing of proportion of adults among patients has been proposed.

  8. Self-reported histories of disease and vaccination against measles, mumps, rubella and varicella in health care personnel in Japan.

    Science.gov (United States)

    Kumakura, Shunichi; Onoda, Keiichi; Hirose, Masahiro

    2014-03-01

    Health care personnel are required to be immune against vaccine-preventable diseases, such as measles, mumps, rubella, and varicella. The aim of this study is to evaluate the accuracy of self-reported histories of disease and vaccination against measles, mumps, rubella, and varicella in order to determine the immune status of health care personnel. A self-reported questionnaire of history of previous disease and vaccination against these diseases was administered to a total of 910 health care personnel in Shimane university hospital in Japan, whose results were compared with serological evidences. There were numerous subjects who did not remember a history of disease (greater than 33% each) and of vaccination (greater than 58% each). Self-reported history of disease and vaccination had high positive predictive value against either disease for testing positive for antiviral antibodies. However, a considerable number of false-negative subjects could be found; 88.9% of subjects for measles, 89.3% for mumps, 62.2% for rubella and 96.3% for varicella in the population who had neither a self-reported history of disease nor a vaccination against each disease. In addition, regardless of the disease in question, a negative predictive value in self-reported history of disease and vaccination was remarkably low. These results suggest that self-reported history of disease and vaccination was not predictive to determine the accurate immune status of health care personnel against measles, mumps, rubella, and varicella. A seroprevalence survey, followed by an adequate immunization program for susceptible subjects, is crucial to prevent and control infection in hospital settings.

  9. Seroprevalence of measles, mumps and rubella among young adults, after 20 years of universal 2-dose MMR vaccination in Israel.

    Science.gov (United States)

    Levine, Hagai; Zarka, Salman; Ankol, Omer E; Rozhavski, Vladi; Davidovitch, Nadav; Aboudy, Yair; Balicer, Ran D

    2015-01-01

    Evidence-based vaccination policy is important for the global and local efforts of achieving control over measles. In 2007, the first Israeli birth cohort to be twice vaccinated during childhood with Measles-Mumps-Rubella vaccine reached adulthood. In parallel, Israel experienced its largest measles outbreak since 1994. We aimed to assess the seroprevalence of measles IgG antibodies and concordance with rubella and mumps seroprevalence among young Israeli adults born 1988-9 in comparison to previous birth cohorts, in order to inform evidence based prevention policy. We conducted a seroprevalence study of IgG antibodies among 439 Israeli adults born in 1988-9, based on a representative sample of sera collected at age 18-19 upon recruitment to mandatory military service in 2007. In total, 85.7% were seropositive for measles as compared with 95.6% in the 1996 recruitment (P Rubella seropositivity among measles seropositives was 90.4%, significantly (P < 0.001) higher than 72.1% among measles seronegatives. Mumps seropositivity among measles seropositives was 87.0%, significantly (P < 0.001) higher than 62.3% among measles seronegatives. Results were similar for Israeli-born only. Our findings indicate that measles seroprevalence decreased after the last change in vaccination policy and reach sub-optimal level. Until global eradication is reached, a proactive vaccination program to supplement routine childhood vaccination program should be considered in Israel and in other countries.

  10. Mumps orchitis in the post-vaccine era (1967-2009): a single-center series of 67 patients and review of clinical outcome and trends.

    Science.gov (United States)

    Ternavasio-de la Vega, Hugo-Guillermo; Boronat, Mauro; Ojeda, Antonio; García-Delgado, Yaiza; Angel-Moreno, Alfonso; Carranza-Rodríguez, Cristina; Bellini, Raquel; Francès, Adela; Nóvoa, Francisco Javier; Pérez-Arellano, José-Luis

    2010-03-01

    Since the introduction of the mumps vaccine, the age of appearance of mumps infection has shifted from children to adolescents and young adults, groups with a higher incidence of disease complications and sequelae. During the years 2000-2001, the Gran Canaria Island was part of an epidemic of mumps. In that period, our institution attended 67 cases of serologically confirmed acute mumps orchitis, the most serious complication of mumps infection in young postpubertal males. We conducted a descriptive and prospective study of this cohort and extensively reviewed the literature from 1967 (the year the first mumps vaccine was introduced) to 2009. Fifty-six patients were admitted because of general impairment and were treated with alpha-interferon. Sixty-six patients presented parotitis previous to orchitis (interval from parotitis to orchitis, 4.9 d). Orchitis was unilateral in 89.5% and bilateral in 10.4% of cases. More than 98% of patients had orchitis-associated fever. Nine patients had clinical and biochemical data showing acute mumps meningitis, and 11 had subclinical pancreatitis. The mean duration of symptoms was 4.6 days (range, 1-9). During the acute phase, more than 41% of the evaluated testes had a volume >25 mL. Acute hormonal disturbances were highly prevalent. These included decreased levels of testosterone and inhibin B with low or normal levels of gonadotropins in 35% of subjects, and, to our knowledge not previously reported, an atypical hormonal pattern consisting of low levels of free testosterone and inhibin B, along with increased measures of luteinizing hormone but low or normal follicle-stimulating hormone levels (11% of cases). During the follow-up period (mean, 331 d) a high incidence of sperm disturbance was found.

  11. Holistic Nursing Intervention for Mumps%流行性腮腺炎整体护理干预

    Institute of Scientific and Technical Information of China (English)

    谢冬云

    2015-01-01

    Objective To summarize the clinical features of mumps in children and explore the corresponding nursing intervention. Methods 50 children with mumps admitted in our hospital from June 2011 to October 2014 were divided into the experimental group and the control group with 25 children in each in accordance with the sealed envelope method, treated by the holistic nurs-ing and conventional nursing, respectively. And the nursing efficacy was compared between the two groups. Results Patients with silent infection of mumps and early mumps patients are all the sources of infection of mumps. Mumps frequently occurs in children of school age. Most of the children have no precursory symptoms. The complications include meningitis, orchitis, oophoritis and pancreatitis. The incidence of complications was 4.0%in the experimental group, and 16.0% in the control group, the level of sat-isfaction of the children's families was 96.0% in the experimental group, and 80.0% in the control group, the difference between the two groups was statistically significant(P<0.05). Conclusion Mumps seriously affects the healthy growth of children. Early find-ing, early treatment, early nursing, active prevention and treatment of the complications can promote the recovery and improve the prognosis. Holistic nursing has higher clinical application effect, so it is worthy of promotion.%目的:总结流行性腮腺炎患儿的临床特点,探讨护理措施。方法随机选取2011年6月—2014年10月该院流行性腮腺炎患儿50例,按信封法将其分成实验组25例,对照组25例,分别给予常规护理、整体护理,对比护理效果。结果隐性感染者和早期病人均为腮腺炎传染源,好发于学龄儿童,多数患儿无前驱症状,并发症包括脑膜炎、睾丸炎、卵巢炎以及胰腺炎。实验组并发症发生率为4.0%,患儿家属满意度为96.0%,与对照组的16.0%、80.0%比较,差异有统计学意义(P<0.05)。结论流行

  12. 乙型脑炎减毒活疫苗细菌内毒素检查方法及质量标准的建立%Establishment of the inspection methods and quality criteria for bacterial endotoxin of live-attenuated vaccine of encephalitis B virus

    Institute of Scientific and Technical Information of China (English)

    李红芳; 陈继军; 王建军; 王伟; 杨博涵; 李守丽; 邹勇

    2009-01-01

    目的 建立乙型脑炎减毒活疫苗细菌内毒素检测的方法及质量标准.方法 参照(三部)中细菌内毒素检查法检测,并与家兔热原实验结果进行对比.结果 使用凝胶限量法检测乙型脑炎减毒活疫苗细菌内毒素,限值为40 EU/mL,即将样品稀释至160倍,在该稀释度下样品对试验没有干扰.结论 该方法简便、灵敏、结果可靠,可用于乙型脑炎减毒活疫凿中间产品的细菌内毒素检查.%Objective To establish the inspection methods and quality criteria for bacterial en- dotoxin of live-attenuated vaccine of encephalitis B virus. Methods The inspecting method for bacterial endotoxin from Pharmacopoeia of the People's Republic of China (3 ed) was employed and the results were compared with the results of rabbit pyrogen test. Results Bacterial endo- toxin of live-attenuated vaccine of encephalitis B virus was detected by gel-clot limit test,the detection limit was 40 EU/mL,namely,160-fold dilution of the sample. In this dilution,no inter- ference of samples to the endotoxin test was observed. Conclusion The method is convenient, sensitive and reliable and may be used for bacterial endotoxin inspection of intermediate products of live-attenuated vaccine of encephalitis B virus.

  13. Immune response to the mumps component of the MMR vaccine in the routine of immunisation services in the Brazilian National Immunisation Program

    Directory of Open Access Journals (Sweden)

    Eliane Matos dos Santos

    2014-06-01

    Full Text Available A non-controlled longitudinal study was conducted to evaluate the combined vaccine against measles, mumps and rubella (MMR immunogenicity in 150 children vaccinated in the routine of three health units in the city of Rio de Janeiro, Brazil, 2008-2009, without other vaccines administered during the period from 30 days before to 30 days after vaccination. A previous study conducted in Brazil in 2007, in 1,769 children ranging from 12-15 months of age vaccinated against yellow fever and MMR simultaneously or at intervals of 30 days or more between doses, had shown low seroconversion for mumps regardless of the interval between administration of the two vaccines. The current study showed 89.5% (95% confidence interval: 83.3; 94.0 seroconversion rate for mumps. All children seroconverted for measles and rubella. After revaccination, high antibody titres and seroconversion rates were achieved against mumps. The results of this study and others suggest that two MMR doses confer optimal immunoresponses for all three antigens and the possible need for additional doses should be studied taking into account not only serological, but also epidemiological data, as there is no serological correlate of protection for mumps.

  14. Measles and mumps among service members and other beneficiaries of the U.S. Military Health System, January 2007-December 2014.

    Science.gov (United States)

    Daniele, Denise O; Clark, Leslie L; Hunt, Devin J; O'Donnell, Francis L

    2015-02-01

    Measles and mumps are highly communicable infectious diseases whose causative viruses are spread through airborne droplets and infected surfaces. Individuals at highest risk are infants and unvaccinated individuals. Despite effective vaccines, there have been recent increases in incidence in the U.S. of both infections. During the surveillance period, there were 14 confirmed measles cases and 99 confirmed mumps cases among U.S. military members and other beneficiaries of the U.S. Military Health System. Only one of the confirmed cases of measles was in a service member. Children aged 5 years and younger accounted for the greatest proportion of confirmed measles cases (50.0%); the greatest proportions of confirmed mumps cases were for children aged 1-5 years and adults aged 26-30 years (22.2% and 17.2%, respectively). California had more cases of both measles and mumps than any other state. Recent trends in measles and mumps in civilian populations in the U.S. highlight the importance of primary and booster vaccinations.

  15. Evaluation of Measles-Mumps-Rubella Vaccination Among Newly Arrived Refugees.

    Science.gov (United States)

    Lee, Deborah; Weinberg, Michelle; Benoit, Stephen

    2017-05-01

    To assess US availability and use of measles-mumps-rubella (MMR) vaccination documentation for refugees vaccinated overseas. We selected 1500 refugee records from 14 states from March 2013 through July 2015 to determine whether overseas vaccination records were available at the US postarrival health assessment and integrated into the Advisory Committee on Immunization Practices schedule. We assessed number of doses, dosing interval, and contraindications. Twelve of 14 (85.7%) states provided data on 1118 (74.5%) refugees. Overseas records for 972 (86.9%) refugees were available, most from the Centers for Disease Control and Prevention's Electronic Disease Notification system (66.9%). Most refugees (829; 85.3%) were assessed appropriately for MMR vaccination; 37 (3.8%) should have received MMR vaccine but did not; 106 (10.9%) did not need the MMR vaccine but were vaccinated. Overseas documentation was available at most clinics, and MMR vaccinations typically were given when needed. Further collaboration between refugee health clinics and state immunization information systems would improve accessibility of vaccination documentation.

  16. PolyMUMPs MEMS device to measure mechanical stiffness of single cells in aqueous media

    Science.gov (United States)

    Warnat, S.; King, H.; Forbrigger, C.; Hubbard, T.

    2015-02-01

    A method of experimentally determining the mechanical stiffness of single cells by using differential displacement measurements in a two stage spring system is presented. The spring system consists of a known MEMS reference spring and an unknown cellular stiffness: the ratio of displacements is related to the ratio of stiffness. A polyMUMPs implementation for aqueous media is presented and displacement measurements made from optical microphotographs using a FFT based displacement method with a repeatability of ~20 nm. The approach was first validated on a MEMS two stage spring system of known stiffness. The measured stiffness ratios of control structures (i) MEMS spring systems and (ii) polystyrene microspheres were found to agree with theoretical values. Mechanical tests were then performed on Saccharomyces cerevisiae (Baker’s yeast) in aqueous media. Cells were placed (using a micropipette) inside MEMS measuring structures and compressed between two jaws using an electrostatic actuator and displacements measured. Tested cells showed stiffness values between 5.4 and 8.4 N m-1 with an uncertainty of 11%. In addition, non-viable cells were tested by exposing viable cells to methanol. The resultant mean cell stiffness dropped by factor of 3 × and an explicit discrimination between viable and non-viable cells based on mechanical stiffness was seen.

  17. Structure-function analysis of two variants of mumps virus hemagglutinin-neuraminidase protein

    Directory of Open Access Journals (Sweden)

    Gerardo Santos-López

    2009-02-01

    Full Text Available A point mutation from guanine (G to adenine (A at nucleotide position 1081 in the hemagglutinin-neuraminidase (HN gene has been associated with neurovirulence of Urabe AM9 mumps virus vaccine. This mutation corresponds to a glutamic acid (E to lysine (K change at position 335 in the HN glycoprotein. We have experimentally demonstrated that two variants of Urabe AM9 strain (HN-A1081 and HN-G1081 differ in neurotropism, sialic acidbinding affinity and neuraminidase activity. In the present study, we performed a structure-function analysis of that amino acid substitution; the structures of HN protein of both Urabe AM9 strain variants were predicted. Based on our analysis, the E/K mutation changes the protein surface properties and to a lesser extent their conformations, which in turn reflects in activity changes. Our modeling results suggest that this E/K interchange does not affect the structure of the sialic acid binding motif; however, the electrostatic surface differs drastically due to an exposed short alpha helix. Consequently, this mutation may affect the accessibility of HN to substrates and membrane receptors of the host cells. Our findings appear to explain the observed differences in neurotropism of these vaccine strains.

  18. Nonspecific native elution of proteins and mumps virus in immunoaffinity chromatography.

    Science.gov (United States)

    Brgles, Marija; Sviben, Dora; Forčić, Dubravko; Halassy, Beata

    2016-05-20

    Immunoaffinity chromatography, based on the antigen-antibody recognition, enables specific purification of any antigen (protein, virus) by its antibody. The problem with immunoaffinity chromatography is the harsh elution conditions required for disrupting strong antigen-antibody interactions, such as low pH buffers, which are often deleterious for the immobilized protein and the protein to be isolated since they can also disrupt the intramolecular forces. Therefore, immunoaffinity chromatography can only be partially used for protein and virus purification. Here we report on a nonspecific elution in immunoaffinity chromatography using native conditions by elution with amino acid solution at physiological pH for which we suppose possible competing mechanism of action. Elution potential of various amino acid solutions was tested using immunoaffinity columns specific for ovalbumin and mumps virus, and protein G affinity column. Results have shown that the most successful elution solutions were those containing imidazole and arginine of high molarity. Imidazole represents aromatic residues readily found at the antigen-antibody interaction surface and arginine is most frequently found on protein surface in general. Therefore, results on their eluting power in immunoaffinity chromatography, which increases with increasing molarity, are in line with the competing mechanism of action. Virus immunoaffinity chromatography resulted in removal on nonviable virus particles, which is important for research and biotechnology purposes. In addition, amino acids are proven stabilizers for proteins and viruses making approach presented in this work a very convenient purification method.

  19. [Clinical Review of Hypospermatogenesis in Patients with a Previous Episode of Mumps Orchitis].

    Science.gov (United States)

    Takeshima, Teppei; Yumura, Yasushi; Iwasaki, Akira; Noguchi, Kazumi

    2015-06-01

    This study included 10 patients who had developed mumps orchitis previously and had visited our hospital from January 1997 to November 2007. The present illness, testicular volume and semen analysis of 7 of these patients were retrospectively investigated. Semen analyses and pregnancy statuses were followed up over time. The mean age of the 7 patients was 33 years (range, 21-43 years). Four patients had unilateral (right side) orchitis, and three had bilateral orchitis. In the unilateral orchitis group, 1 patient had an atrophic testis. Findings of semen analysis were severe oligozoospermia in three and mild oligozoospermia in one. None of the patients in the bilateral orchitis group, had atrophic testes. Findings of semen analysis were azoospermia in one and severe oligozoospermia in two patients. Findings of semen analysis in most patients improved gradually, and wives of 2 patients eventually achieved pregnancy. Dysfunction of seminiferous tubules in the diseased testis is thought to be reversible when treated adequately in the initial phase. In the patients not conceiving successfully, testicular sperm extraction (TESE) and assisted reproductive technique (ART) are thought to be effective ways to achieve pregnancy.

  20. Mouse Testicular Cell Type-Specific Antiviral Response against Mumps Virus Replication

    Science.gov (United States)

    Wu, Han; Zhao, Xiang; Wang, Fei; Jiang, Qian; Shi, Lili; Gong, Maolei; Liu, Weihua; Gao, Bo; Song, Chengyi; Li, Qihan; Chen, Yongmei; Han, Daishu

    2017-01-01

    Mumps virus (MuV) infection has high tropism to the testis and usually leads to orchitis, an etiological factor in male infertility. However, MuV replication in testicular cells and the cellular antiviral responses against MuV are not fully understood. The present study showed that MuV infected the majority of testicular cells, including Leydig cells (LC), testicular macrophages, Sertoli cells (SC), and male germ cells (GC). MuV was replicated at relatively high efficiencies in SC compared with LC and testicular macrophages. In contrast, MuV did not replicate in male GC. Notably, testicular cells exhibited different innate antiviral responses against MuV replication. We showed that interferon β (IFN-β) inhibited MuV replication in LC, macrophages, and SC, which were associated with the upregulation of major antiviral proteins. We provided primary evidence that autophagy plays a role in blocking MuV replication in male GC. Autophagy was also involved in limiting MuV replication in testicular macrophages but not in Leydig and SC. These findings indicate the involvement of the innate defense against MuV replication in testicular cells. PMID:28239382

  1. New preventive strategy to eliminate measles, mumps and rubella from Europe based on the serological assessment of herd immunity levels in the population.

    Science.gov (United States)

    Plans, P

    2013-07-01

    Herd immunity blocks the transmission of measles, mumps and rubella in a population group when the prevalence of positive serologic results (p) is higher than a critical value (p c), known as the herd immunity threshold. A new preventive strategy should be developed in order to achieve the elimination of measles, rubella and mumps in Europe based on the serological assessment of herd immunity levels in different population groups. This strategy could detect population groups without herd immunity (p herd immunity and prevent outbreaks. The serological assessment of herd immunity levels in Catalonia, Spain, showed that herd immunity had not been established for measles and mumps in schoolchildren (5-9 years of age) and youths/younger adults (15-29 years of age), and that the additional vaccination coverage required to establish herd immunity in these groups was 1-7%. The new preventive strategy should be used to detect priority population groups for preventive and surveillance activities in European countries.

  2. Addressing issues of vaccination literacy and psychological empowerment in the measles-mumps-rubella (MMR) vaccination decision-making: a qualitative study.

    Science.gov (United States)

    Fadda, Marta; Depping, Miriam K; Schulz, Peter J

    2015-09-02

    Whether or not to vaccinate one's child is one of the first health-related decisions parents have to make after their child's birth. For the past 20 years, the share of parents choosing not to immunize their children has increased in many countries, for various reasons. Among these, rumors affirming that vaccinations contain dangerous chemicals or might trigger severe chronic diseases have negatively affected parental attitudes towards pediatric immunizations, particularly the vaccination against measles, mumps and rubella (MMR), raising a number of public health concerns. The primary aim of this qualitative study is to understand what drives parents' decision, giving special attention to vaccination literacy and psychological empowerment in such a context. Twenty individual semi-structured interviews were conducted in the Canton of Ticino (Switzerland) between January and June 2014. Participants were either mothers or fathers of children less than 1 year old living in Switzerland. An inductive thematic analysis was performed to identify the main themes with regard to vaccination literacy and psychological empowerment in the MMR vaccination decision-making. Parents' reports yielded four main themes: (a) the paradox of the free choice, referring to the misinterpretation of current vaccination policies; (b) giving up the power, pointing at the outcomes of a low perceived competence; (c) a far-reaching decision, reflecting the importance attributed to the MMR choice and the different levels of impact the decision can have; (d) the demand for shared-decision making, referring to the parental needs in relation to the child's healthcare provider. Understanding what drives parents' management of their children's immunization schedule in terms of vaccination literacy and psychological empowerment can help health professionals to communicate more effectively with parents in order to facilitate an informed decision, and stakeholders to design tailored health education

  3. Difficulties in eliminating measles and controlling rubella and mumps: a cross-sectional study of a first measles and rubella vaccination and a second measles, mumps, and rubella vaccination.

    Directory of Open Access Journals (Sweden)

    Zhifang Wang

    Full Text Available BACKGROUND: The reported coverage of the measles-rubella (MR or measles-mumps-rubella (MMR vaccine is greater than 99.0% in Zhejiang province. However, the incidence of measles, mumps, and rubella remains high. In this study, we assessed MMR seropositivity and disease distribution by age on the basis of the current vaccination program, wherein the first dose of MR is administered at 8 months and the second dose of MMR is administered at 18-24 months. METHODS: Cross-sectional serological surveys of MMR antibodies were conducted by collecting epidemiological data in Zhejiang province, China in 2011. In total, 1015 participants were randomly selected from two surveillance sites. Serum MMR-specific immunoglobulin G levels were tested by enzyme-linked immunosorbent assay. The geometric mean titers and seroprevalence with 95% confidence intervals (CIs were calculated by age and gender. Proportions of different dose of vaccine by age by vaccine were also identified. Statistically significant differences between categories were assessed by the Chi-square test. RESULTS: Over 95% seroprevalence rates of measles were seen in all age groups except <7 months infants. Children aged 5-9 years were shown lower seropositivity rates of mumps while elder adolescences and young adults were presented lower rubella seroprevalence. Especially, rubella seropositivity was significantly lower in female adults than in male. Nine measles cases were unvaccinated or unknown vaccination history. Among them, 66.67% (6/9 patients were aged 20-29 years while 33.33% (3/9 were infants aged 8-12 months. In addition, 57.75% (648/1122 patients with mumps were children aged 5-9 years, and 50.54% (94/186 rubella cases were aged 15-39 years. CONCLUSIONS: A timely two-dose MMR vaccination schedule is recommended, with the first dose at 8 months and the second dose at 18-24 months. An MR vaccination speed-up campaign may be necessary for elder adolescents and young adults, particularly

  4. Comparison of automated chemiluminescence immunoassays with capture enzyme immunoassays for the detection of measles and mumps IgM antibodies in serum.

    Science.gov (United States)

    Haywood, Becky; Patel, Mauli; Hurday, Samantha; Copping, Ruth; Webster, Daniel; Irish, Dianne; Haque, Tanzina

    2014-02-01

    Outbreaks of measles and mumps occur regularly in the UK. Rapid diagnosis of acute infection is important for both infection control and epidemiological purposes. The objective of this study was to compare the performance of an automated platform (DiaSorin Liaison(®), Saluggia, Italy) with a manual capture enzyme immunoassay (EIA; Microimmune, Hounslow, UK) for the detection of measles and mumps IgM antibodies in serum from symptomatic individuals. Ninety sera tested previously for measles (n=50) and mumps (n=40) IgM using the manual EIA were tested retrospectively using the DiaSorin Liaison(®) and the results compared. Sensitivity, specificity, inter-assay variability and intra-assay variability of the Liaison(®) assays were calculated. Sensitivity and specificity of the Liaison(®) assay for measles IgM were 92% and 100% respectively, with inter-assay variation of 14.1% and intra-assay variation of 12.5%. The sensitivity and specificity of the mumps IgM Liaison(®) assay were 88% and 95% respectively, with an inter-assay and intra-assay variation of 13.9% and 5.3% respectively. Both the measles and mumps IgM Liaison(®) assays gave fewer equivocal results than the EIA. Neither Liaison(®) IgM assay showed any cross-reactivity with sera positive against other viruses, however the measles IgM EIA cross-reacted with parvovirus IgM. The automated Liaison(®) assays are more specific, cheaper and less labour-intensive compared to the manual EIA. The Liaison(®) assays benefit from reduced number of equivocal results compared to the EIA for both measles and mumps IgM. This allows clinical decisions to be made accurately and in a timely manner.

  5. Photonic Crystal Fiber Attenuator

    Institute of Scientific and Technical Information of China (English)

    Joo; Beom; Eom; Hokyung; Kim; Jinchae; Kim; Un-Chul; Paek; Byeong; Ha; Lee

    2003-01-01

    We propose a novel fiber attenuator based on photonic crystal fibers. The difference in the modal field diameters of a conventional single mode fiber and a photonic crystal fiber was used. A variable optical attenuator was also achieved by applying macro-bending on the PCF part of the proposed attenuator

  6. 麻疹减毒活疫苗S191生产用毒株的遗传稳定性%Genetic Stability of S191 Strain for Production of Live Attenuated Measles Vaccine

    Institute of Scientific and Technical Information of China (English)

    赵炜炜; 封多佳; 董小曼

    2009-01-01

    目的 分析麻疹减毒活疫苗S191生产用毒株病毒结构基因的遗传稳定性.方法 将北京天坛生物制品股份有限公司(天坛生物)用于麻疹疫苗生产的S191株25代病毒(S191-BJ25)传至29代(S191-BJ29),上海生物制品研究所保存的S191株24代病毒(S191-SH24)传至33代(S191-SH33).从S191株传代病毒中提取RNA,对病毒结构基因片段N、M、F,H进行扩增及测序.将测序结果与GenBank中1994年收录的S191株麻疹病毒的相应序列进行比较分析.结果 S191-BJ25传代病毒N、M、F、H 4个基因的总突变率为0.02%,S191-SH2A传代病毒为0.15%;与1994年的S191疫苗株相比,S191-BJ25传代病毒N、M、F、H 4个基因的总突变率为0.3%,S191-SH24传代病毒为0.4%.结论 目前天坛生物使用的麻疹疫苗S191株生产用三级种子库具有可靠的遗传稳定性,从主代种子到疫苗的传代过程中,N、M、F、H结构基因表现出稳定的分子遗传特征.目前使用的S191毒株的4个结构基因较1994年以前的疫苗株发生了变化.但目前没有证据表明这些变化对免疫原性产生不利影响.%Objective To analyze the genetic stability of structural gene of S191 strain for production of live attenuated measles vaccine.Methods The S191 strain for production of measles vaccine by Beijing Tiantan Biological Products Co.Ltd Was subcuhured from passage 25(S191-BJ25)to 29 (S191-BJ29),and that by Shanghai Institute of Biological Products from passage 24(S191-SH24)to 33(S191-SH33).RNAs were extracted from the subcultured strains for amplification and sequencing of structural gene fragments N,M,F and H.The sequencing results were compared with those of the corresponding sequences of S191 strain included in GenBank in 1994.Results The total mutation rate of N,M,F and H genes of subcultured S191-BJ25 Was 0.02%.while that of subcuhured S191-SH24 was 0.15%.Compared with those of S191 strain included in GenBank in 1994,the total mutation rate of the four genes of

  7. Interaction of mumps virus V protein variants with STAT1-STAT2 heterodimer: experimental and theoretical studies

    Directory of Open Access Journals (Sweden)

    Reyes-Leyva Julio

    2010-10-01

    Full Text Available Abstract Background Mumps virus V protein has the ability to inhibit the interferon-mediated antiviral response by inducing degradation of STAT proteins. Two virus variants purified from Urabe AM9 mumps virus vaccine differ in their replication and transcription efficiency in cells primed with interferon. Virus susceptibility to IFN was associated with insertion of a non-coded glycine at position 156 in the V protein (VGly of one virus variant, whereas resistance to IFN was associated with preservation of wild-type phenotype in the V protein (VWT of the other variant. Results VWT and VGly variants of mumps virus were cloned and sequenced from Urabe AM9 vaccine strain. VGly differs from VWT protein because it possesses an amino acid change Gln103Pro (Pro103 and the Gly156 insertion. The effect of V protein variants on components of the interferon-stimulated gene factor 3 (ISGF3, STAT1 and STAT2 proteins were experimentally tested in cervical carcinoma cell lines. Expression of VWT protein decreased STAT1 phosphorylation, whereas VGly had no inhibitory effect on either STAT1 or STAT2 phosphorylation. For theoretical analysis of the interaction between V proteins and STAT proteins, 3D structural models of VWT and VGly were predicted by comparing with simian virus 5 (SV5 V protein structure in complex with STAT1-STAT2 heterodimer. In silico analysis showed that VWT-STAT1-STAT2 complex occurs through the V protein Trp-motif (W174, W178, W189 and Glu95 residue close to the Arg409 and Lys415 of the nuclear localization signal (NLS of STAT2, leaving exposed STAT1 Lys residues (K85, K87, K296, K413, K525, K679, K685, which are susceptible to proteasome degradation. In contrast, the interaction between VGly and STAT1-STAT2 heterodimer occurs in a region far from the NLS of STAT2 without blocking of Lys residues in both STAT1 and STAT2. Conclusions Our results suggest that VWT protein of Urabe AM9 strain of mumps virus may be more efficient than VGly to

  8. Tracer attenuation in groundwater

    Science.gov (United States)

    Cvetkovic, Vladimir

    2011-12-01

    The self-purifying capacity of aquifers strongly depends on the attenuation of waterborne contaminants, i.e., irreversible loss of contaminant mass on a given scale as a result of coupled transport and transformation processes. A general formulation of tracer attenuation in groundwater is presented. Basic sensitivities of attenuation to macrodispersion and retention are illustrated for a few typical retention mechanisms. Tracer recovery is suggested as an experimental proxy for attenuation. Unique experimental data of tracer recovery in crystalline rock compare favorably with the theoretical model that is based on diffusion-controlled retention. Non-Fickian hydrodynamic transport has potentially a large impact on field-scale attenuation of dissolved contaminants.

  9. The Measels-Mumps-Rubella Vaccination from a health political and economical point of view

    Directory of Open Access Journals (Sweden)

    Habl, Claudia

    2007-11-01

    Full Text Available Introduction: Measels, Mumps and Rubella (MMR are highly contagious infectious diseases which may lead to severe complications. These diseases are vaccine-preventable. The present Health Technology Assessment report (report on technological consequences, HTA report was commissioned by the German Institute of Medical Documentation and Information (DIMDI and addresses various aspects of the MMR vaccination, the key question being how the MMR immunisation coverage rate can be increased in Germany. Objectives: The objectives of this report were to describe the benefits of the MMR vaccination for Germany and to analyse how the desired MMR immunisation coverage of >95% can be achieved. Methods: A systematic literature search was performed in 29 literature data bases. Particularly for epidemiological data and information on vaccination programs, this systematic search was supplemented by an extensive hand search, written and oral enquiries, as well as interviews with experts. A total of 200 texts were used to prepare this report. Results: At 92.5% (as of 2004 based on the whole of Germany, the current immunisation coverage for measles in children is above the weighted EC-15-average of 90.67%. Statements can only be made regarding the probability of illness for measles, as no data is available for mumps and rubella. With 2.8 infections (per 100,000 residents in 2006, Germany has not achieved the WHO target. Of cases submitted to the laboratory, only 32% were validated by diagnostic laboratory findings and 45% confirmed clinical-epidemiologically. There are only few economic analyses of vaccination programs in Germany. In international publications, mainly measels are validated economically. An analysis of the cost of measles for Germany shows potential cost savings. Unfortunately, no complete economic evaluation (cost-effectiveness, cost-benefit, or cost-utility analyses for MMR vaccination has been performed for Germany. Analyses conducted in the US

  10. Seroprevalence of Measles, Mumps, and Rubella Antibodies in College Students in Mumbai, India.

    Science.gov (United States)

    Gohil, Devanshi J; Kothari, Sweta T; Chaudhari, Amol B; Gunale, Bhagwat K; Kulkarni, Prasad S; Deshmukh, Ranjana A; Chowdhary, Abhay S

    2016-04-01

    Measles, Mumps, and Rubella (MMR) are vaccine preventable viral infections, which cause significant mortality and morbidity globally. Increased incidence rates of these infectious diseases are observed in young adults. Information on seroprevalence data on MMR in India is limited. The objective of this study was to determine the prevalence of IgG antibodies against MMR among young adults. This was a descriptive cross-sectional study involving 192 healthy college students from Maharshi Dayanand College, Mumbai. The project was approved by the Institutional Ethics Committee of Haffkine Institute. Between December 2012 and September 2013, blood samples were collected from individuals of age 18-23 years after obtaining written informed consent from them. The quantitative determination of IgG antibodies in serum specimens against MMR was determined using enzyme linked immunosorbent assay. Data on history of vaccination were also collected from participants. Among 192 healthy college students (age 18-23 years), MMR seroprevalence was 91%, 97%, and 88%, respectively. The overall seropositivity of MMR was 79%. The highest level of seronegativity was seen with regards to rubella-specific antibodies in 12% of cases. About 96% of the participants did not know about their vaccination history while none of the participants knew about their history of MMR infections. Despite unknown vaccination status, a majority of college students in our study were found seropositive for all three infections, which indicate natural boosting. However, the proportion of seronegativity for measles and rubella was relatively higher. Especially since the study population belonged to reproductive age group, there is a concern of congenital rubella syndrome in the offspring. Although a larger multicentric study is required to confirm the findings, the results indicate that a dose of measles-rubella (MR) vaccine should be offered to these college students.

  11. Mumps virus Enders strain is sensitive to interferon (IFN) despite encoding a functional IFN antagonist.

    Science.gov (United States)

    Young, D F; Galiano, M C; Lemon, K; Chen, Y-H; Andrejeva, J; Duprex, W P; Rima, B K; Randall, R E

    2009-11-01

    Although the Enders strain of mumps virus (MuV) encodes a functional V protein that acts as an interferon (IFN) antagonist, in multi-cycle growth assays MuV Enders grew poorly in naïve ('IFN-competent' Hep2) cells but grew to high titres in 'IFN-compromised' Hep2 cells. Even so, the growth rate of MuV Enders was significantly slower in 'IFN-compromised' Hep2 cells when compared with its replication rate in Vero cells and with the replication rate of parainfluenza virus type 5 (a closely related paramyxovirus) in both naïve and 'IFN-compromised' Hep2 cells. This suggests that a consequence of slower growth is that the IFN system of naïve Hep2 cells can respond quickly enough to control the growth of MuV Enders. This is supported by the finding that rapidly growing variants of MuV Enders that were selected on 'IFN-compromised' Hep2 cells (i.e. in the absence of any selection pressure exerted by the IFN response) also grew to high titres on naïve Hep2 cells. Sequencing of the complete genome of one of these variants identified a single point mutation that resulted in a substitution of a conserved asparagine by histidine at position 498 of the haemagglutinin-neuraminidase protein, although this mutation was not present in all rapidly growing variants. These results support the concept that there is a race between the ability of a cell to detect and respond to virus infection and the ability of a virus to block the IFN response. Importantly, this emphasizes that factors other than viral IFN antagonists influence the sensitivity of viruses to IFN.

  12. Treatment of recalcitrant warts with intralesional measles, mumps, and rubella vaccine: a promising approach.

    Science.gov (United States)

    Nofal, Ahmad; Nofal, Eman; Yosef, Ayman; Nofal, Hager

    2015-06-01

    Recalcitrant warts represent a frustrating challenge for both patients and physicians. Although many destructive and immunotherapeutic modalities are available for the treatment of warts, an ideal, universally effective approach has not been explored to date. Recently, intralesional antigen immunotherapy has shown promising efficacy in the treatment of warts. The aim of the study was to evaluate the efficacy and safety of intralesional measles, mumps, and rubella (MMR) vaccine in the treatment of recalcitrant warts. The study included 70 adult patients with multiple recalcitrant extragenital warts of different sizes and durations, with or without distant warts. They were directly injected, without a pre-sensitization skin test, with 0.3 intralesional MMR vaccine into the largest wart at 2-week intervals until complete clearance or for a maximum of five treatments. Follow-up was made every month for six months to detect any recurrence. Sixty-five patients, 35 men and 30 women, completed the study, and five patients discontinued for various reasons. Complete clearance of the lesions was observed in 41 patients (63%), partial response in 15 patients (23%), and no response in nine patients (14%). Complete response was demonstrated in 74.5% of those presenting with distant warts. Side effects were mild and insignificant in the form of pain during injection, itching, erythema, and edema at the site of injection and flu-like symptoms. Recurrence was detected in two patients only. Intralesional immunotherapy by MMR vaccine is a promising, effective, and safe treatment modality for recalcitrant warts. © 2014 The International Society of Dermatology.

  13. No evidence of an increase of bacterial and viral infections following Measles, Mumps and Rubella vaccine.

    Science.gov (United States)

    Stowe, Julia; Andrews, Nick; Taylor, Brent; Miller, Elizabeth

    2009-02-25

    The suggestion that multi-antigen vaccines might overload the immune system has led to calls for single antigen vaccines. In 2003 we showed that rather than an increase there appeared to be a reduced risk of severe bacterial infection in the three months following Measles, Mumps and Rubella vaccine (MMR). The present analysis of illnesses in a general population is based on an additional 10 years of data for bacterial infections and also includes admissions with viral infections. Analyses were carried out using the self-controlled case-series method and separately for bacterial and viral infection cases, using risk periods of 0-30 days, 31-60 days and 61-90 days post MMR vaccine. An analysis was also carried out for those cases which were given MMR and Meningococcal serogroup C (MCC) vaccines concomitantly. A reduced risk was seen in the 0-30-day period for both bacterial infection (relative incidence=0.68, 95% CI 0.54-0.86) and viral infections (relative incidence=0.68, 95% CI 0.49-0.93). There was no increased risk in any period when looking at combined viral or bacterial infections or for individual infections with the single exception of an increased risk in the 31-60 days post vaccination period for herpes infections (relative incidence=1.69, 95% CI 1.06-2.70). For the children given Meningococcal group C vaccines concomitantly no significantly increased risk was seen in either the bacterial (relative incidence=0.54, 95% CI 0.26-1.13) or viral cases (relative incidence=0.46, 95% CI 0.11-1.93). Our study confirms that the MMR vaccine does not increase the risk of invasive bacterial or viral infection in the 90 days after the vaccination and does not support the hypothesis that there is an induced immune deficiency due to overload from multi-antigen vaccines.

  14. Prevalence of antibodies against measles, mumps and rubella in the childhood population in Singapore, 2008-2010.

    Science.gov (United States)

    Ang, L W; Lai, F Y; Tey, S H; Cutter, J; James, L; Goh, K T

    2013-08-01

    We undertook a national paediatric seroprevalence survey of measles, mumps and rubella (MMR) in Singapore to assess the impact of the national childhood immunization programme against these three diseases after introduction of the trivalent MMR vaccine in 1990. The survey involved 1200 residual sera of Singapore residents aged 1-17 years collected from two hospitals between 2008 and 2010. The overall prevalence of antibodies against measles, mumps and rubella was 83∙1% [95% confidence interval (CI) 80∙9-85∙1], 71.8% (95% CI 69∙1-74∙2) and 88∙5% (95% CI 86∙6-90∙2), respectively. For all three diseases, the lowest prevalence was in children aged 1 year (47∙8-62∙3%). The seroprevalence of the vaccinated children declined over time. The national MMR immunization programme is effective in raising the herd immunity of the childhood population, although certain age groups are more susceptible to infection, in particular, those who are not eligible for vaccination at age <15 months.

  15. Booster vaccination with safe, modified, live-attenuated mutants of Brucella abortus strain RB51 vaccine confers protective immunity against virulent strains of B. abortus and Brucella canis in BALB/c mice.

    Science.gov (United States)

    Truong, Quang Lam; Cho, Youngjae; Kim, Kiju; Park, Bo-Kyoung; Hahn, Tae-Wook

    2015-11-01

    Brucella abortus attenuated strain RB51 vaccine (RB51) is widely used in prevention of bovine brucellosis. Although vaccination with this strain has been shown to be effective in conferring protection against bovine brucellosis, RB51 has several drawbacks, including residual virulence for animals and humans. Therefore, a safe and efficacious vaccine is needed to overcome these disadvantages. In this study, we constructed several gene deletion mutants (ΔcydC, ΔcydD and ΔpurD single mutants, and ΔcydCΔcydD and ΔcydCΔpurD double mutants) of RB51 with the aim of increasing the safety of the possible use of these mutants as vaccine candidates. The RB51ΔcydC, RB51ΔcydD, RB51ΔpurD, RB51ΔcydCΔcydD and RB51ΔcydCΔpurD mutants exhibited significant attenuation of virulence when assayed in murine macrophages in vitro or in BALB/c mice. A single intraperitoneal immunization with RB51ΔcydC, RB51ΔcydD, RB51ΔcydCΔcydD or RB51ΔcydCΔpurD mutants was rapidly cleared from mice within 3 weeks, whereas the RB51ΔpurD mutant and RB51 were detectable in spleens until 4 and 7 weeks, respectively. Vaccination with a single dose of RB51 mutants induced lower protective immunity in mice than did parental RB51. However, a booster dose of these mutants provided significant levels of protection in mice against challenge with either the virulent homologous B. abortus strain 2308 or the heterologous Brucella canis strain 26. In addition, these mutants were found to induce a mixed but T-helper-1-biased humoral and cellular immune response in immunized mice. These data suggest that immunization with a booster dose of attenuated RB51 mutants provides an attractive strategy to protect against either bovine or canine brucellosis.

  16. Enzyme immunoassay of mumps virus in cell culture with peroxidase-labelled virus specific monoclonal antibodies and its application for determination of antibodies

    NARCIS (Netherlands)

    Tiel, F.H. van; Kraaijeveld, C.A.; Baller, J.; Harmsen, T.; Oosterlaken, T.A.M.; Snippe, H.

    1988-01-01

    Mumps neutralizing monoclonal antibodies (MAs) were purified and labelled with horseradish peroxidase and used to detect virus-infected Vero cells, which were seeded as monolayers in wells of 96-well plates. This direct enzyme immunoassay (EIA) in cell culture proved to be a sensitive method for

  17. Tolerability of Early Measles-Mumps-Rubella Vaccination in Infants Aged 6-14 Months during a Measles Outbreak in the Netherlands in 2013-2014

    NARCIS (Netherlands)

    Van Der Maas, Nicoline A T; Woudenberg, T.; Hahń, S. J M; De Melker, H. E.

    2016-01-01

    Background. In 2013–2014, a measles outbreak spread through the Netherlands. To protect young infants, measles-mumps-rubella (MMR) vaccination was offered to those aged 6–14 months in municipalities with routine first-dose MMR vaccine coverage of <90%. We assessed the tolerability of this early admi

  18. Enzyme immunoassay of mumps virus in cell culture with peroxidase-labelled virus specific monoclonal antibodies and its application for determination of antibodies

    NARCIS (Netherlands)

    Tiel, F.H. van; Kraaijeveld, C.A.; Baller, J.; Harmsen, T.; Oosterlaken, T.A.M.; Snippe, H.

    1988-01-01

    Mumps neutralizing monoclonal antibodies (MAs) were purified and labelled with horseradish peroxidase and used to detect virus-infected Vero cells, which were seeded as monolayers in wells of 96-well plates. This direct enzyme immunoassay (EIA) in cell culture proved to be a sensitive method for det

  19. 减毒流感活疫苗在2~17岁儿童中的有效性和安全性%Effectiveness and safety of live attenuated influenza vaccine in children of 2 to 17 years old

    Institute of Scientific and Technical Information of China (English)

    汪一龙

    2015-01-01

    Live attenuated influenza vaccine (LAIV) is a Live attenuated influenza vaccine.LAIV has demonstrated significantly greater protection against influenza in healthy children or children with a history of respiratory diseases or with immunodeficiency diseases 2 to17 years of age as compared with TIV.LAIV can prevent influenza more efficient without increasing hospitalization and emergency department visits as compared with TIV.Except for the runny nose and nasal congestion,no excess risk of adverse events have been found among children who were vaccinated with LAIV compared with those vaccinated with TIV.LAIV has the potential in children to stimulate greater local anti-influenza immune responses and its protective effect can extend beyond the year of administration.Vaccining LAIV is convenient and noninvasive for children,it is easily accepted by children and their parents.LAIV offers a effective approach to prevent influenza.%与接种三价灭活流感疫苗(trivalent inactivated influenza vaccine,TIV)相比较,接种减毒流感活疫苗(live attenuated influenza vaccine,LAIV)能明显提高2~17岁健康儿童及患呼吸道疾病、免疫缺陷病儿童的抗流感能力,能更有效预防儿童流感的发生,且不会提高儿童的急诊率和住院率,不会提高除鼻塞、流涕外,任何其他不良反应的发生率.LAIV能使儿童机体产生更强的抗流感免疫反应.接种LAIV1年后,其仍有较高的保护效力.经鼻腔接种LAIV方便且无痛苦,更容易被儿童和家长所接受.LAIV为预防儿童流感的发生提供了一条有效的途径.

  20. THE RESULTS OF STUDY OF THE LEVELS OF SPECIFIC ANTIBODIES TO THE COMBINED INJECTION VACCINES AGAINST INFLUENZA, MEASLES, RUBELLA AND MUMPS AND DT IN CHILDREN WITH CHRONIC PHYSICAL ILLNESS

    Directory of Open Access Journals (Sweden)

    S. M. Haritе

    2014-01-01

    Full Text Available The levels of antibodies to the separate and combined administration of the vaccine plus Grippol® Plus and vaccines against measles, mumps and/or rubella, diphtheria and tetanus (DT in children with chronic medical illnesses, including HIV and organic CNS. Revealed that at low reactogenicity and safety of the vaccine Grippol® Plus, concomitant vaccination does not affect the dynamics of the synthesis (seroprotection, seroconversion, diphtheria, mumps, and rubella antibodies, however, reduces the synthesis of measles antibodies. When combined administration of DT and mumps-measles vaccines + Grippol® Plus suppressed antibody response to a strain of influenza virus A/H3N2. 

  1. Clinical analysis of mumps orchitis%流行性腮腺炎合并睾丸炎的临床分析

    Institute of Scientific and Technical Information of China (English)

    何红迅

    2014-01-01

    目的:探究流行性腮腺炎合并睾丸炎的临床特征,为临床治疗流行性腮腺炎合并睾丸炎提供参考。方法:选取我院2012年2月—2014年8月收治的流行性腮腺炎合并睾丸炎48例,对患者流行病学特征、临床特点、治疗及转归进行回顾性分析。结果:腮腺炎合并睾丸炎患者发病主要集中于13~35岁,以15~25岁青少年为主,患者多表现发热、腮腺肿大、睾丸肿大及压痛等症状。经临床对症治疗、支持治疗及综合护理,病人平均治疗为8d,患者痊愈。结论:流行性腮腺炎合并睾丸炎是流行性腮腺炎的常见的并发症,多见于青少年患者,采用中西医结合能有效治疗流行性腮腺炎合并睾丸炎。%Objective:To explore the clinical characteristics of mumps orchitis, provides the reference for the clinical treatment of mumps orchitis. Methods: 48 cases of mumps orchitis selects my courtyard 2012 February 2014 year August were of patients, epidemiological characteristics, clinical features, treatment and prognosis were retrospectively analyzed. Results:The incidence of patients with mumps orchitis mainly concentrated in 13~35 years old, with 15~25 years old teenagers, patients with multiple manifestations of fever, swollen glands, testicular swelling and tenderness and other symptoms. Treatment and comprehensive nursing by clinical symptomatic treatment, support, the average patient treatment for 8D, the patients were cured. Conclusion:Mumps orchitis is a common complication of mumps, more common in adolescent patients, using traditional Chinese and Western medicine can be effective in the treatment of mumps orchitis.

  2. Stability and efficacy of the 3'-UTR A4G-G5A variant of viral hemorrhagic septicemia virus (VHSV) as a live attenuated immersion VHSV vaccine in olive flounder (Paralichthys olivaceus).

    Science.gov (United States)

    Kim, Sung-Hyun; Kim, Meesun; Choi, Go-Eun; Lee, Jeong Ho; Kang, Jung-Ha; Evensen, Øystein; Lee, Woo-Jai

    2016-02-17

    Viral hemorrhagic septicemia virus (VHSV) is the causative agent of viral hemorrhagic septicemia in fish, a disease that affects a number of teleost fish species including olive flounder (Paralichthys olivaceus). In this study, we assessed the safety and efficacy of two recombinant attenuated VHSV strains, termed A4G-G5A and ΔNV, with the purpose to select the most suitable vaccine strain. The virus strains were passaged in two commercially available cell lines, EPC and RTG-2, and the strains were also tested for residual virulence in zebrafish (Danio rerio). The A4G-G5A strain showed an attenuated growth profile in both the EPC and RTG-2 cell lines compared to wild-type (WT) VHSV (JF-09, genotype IVa), whereas the growth profile of ΔNV was comparable to the WT strains in RTG-2 cells in contrast to EPC cells. Moreover, ΔNV had higher residual virulence compared to A4G-G5A and was highly pathogenic to zebrafish. The A4G-G5A strain was chosen as vaccine candidate and tested for efficacy in in vivo fish studies in the target species, olive flounder, using an immersion vaccine scheme. Groups of fish were immunized with 10(2.5), 10(3.5), 10(4.5), and 10(5.5) TCID50/ml of A4G-G5A giving 5-13.3 cumulative percent mortality (CPM) post immunization. Immunization was followed by a challenge experiment using VHSV-WT. The relative percent survival (RPS) in immunized groups ranged from 81.6% to 100%, correlating with vaccination dose. This study demonstrates that while strain A4G-G5A has retained some residual virulence it confers high level of protection in immunized olive flounder.

  3. Establishment of Master Cell Stock and Working Cell Bank of MDCK Lines and Selection and Evaluation of the Lines as Candidate Viral Substrates for Approval Production of Combinational Canine Attenuated-live Virus Vaccines

    Institute of Scientific and Technical Information of China (English)

    ZHANG De-li; FANG Fu-de; LI Liu-jin; XIA Geng-tian; HE Xu-yu; GAO Bu-xian; BAI Xiao-hong; HUANG Gao-sheng; LIU Shang-gao; YEN Lung-fei

    2002-01-01

    Under the prerequisite that the incidence of cancer or tumor in negative-control nude mice inoculated subcutaneously with primary feline or canine kidney cell cultures purified in vitro at passage 3 was 0(0/22) and 0 (0/10), respectively. The incidence of the progressively-growing malignant tumor(MT) in positive-control nude mice inoculated subcutaneously with Hela cell cultures of KB, X, or NM20/X strain was 10/10, 25/25 and 5/51, respectively. The results showed that the incidence of tumor in nude mice with di-and hyperploid YB strain of MDCK cell during 17 - 23 passages, with hyper- and hypoploid KA strain of MDCK cell during 6 - 8 passages, with hypoploid WB strain of MDCK cell on passage 6, with hyper-and hypopioid H strain of MDCK cell during 8 - 24 passages was 2/24, 6/10, 5/10 and 10/15, respectively. The chromosomal analysis results showed that the ratio of difference in the rate of modal chromosome number between high(mcs + n) and lowest (mcs)passages was not more than 5- 15% and the structure aberrations was generally 0-3%. These results proved that the genetic characteristics of chromosomal number of cell lines determines their tumorigenicity, but it is species-specific. MDCK line has tumorigenicity no matter what its chromosome karyotype is, at least it has very low tumorigenicity even when its modal chromosome number is hypoploid. It is thus evident that MDCK cell of WB or H strain can be approved as substrate for the preparation of attenuated viral vaccines, but MDCK cell of YB or KA strain can not be approved as substrate for the preparation of attenuated viral vaccines.

  4. Thermal Actuation Based 3-DoF Non-Resonant Microgyroscope Using MetalMUMPs.

    Science.gov (United States)

    Shakoor, Rana Iqtidar; Bazaz, Shafaat Ahmed; Kraft, Michael; Lai, Yongjun; Masood Ul Hassan, Muhammad

    2009-01-01

    High force, large displacement and low voltage consumption are a primary concern for microgyroscopes. The chevron-shaped thermal actuators are unique in terms of high force generation combined with the large displacements at a low operating voltage in comparison with traditional electrostatic actuators. A Nickel based 3-DoF micromachined gyroscope comprising 2-DoF drive mode and 1-DoF sense mode oscillator utilizing the chevron-shaped thermal actuators is presented here. Analytical derivations and finite element simulations are carried out to predict the performance of the proposed device using the thermo-physical properties of electroplated nickel. The device sensitivity is improved by utilizing the dynamical amplification of the oscillation in 2-DoF drive mode using an active-passive mass configuration. A comprehensive theoretical description, dynamics and mechanical design considerations of the proposed gyroscopes model are discussed in detail. Parametric optimization of gyroscope, its prototype modeling and fabrication using MetalMUMPs has also been investigated. Dynamic transient simulation results predicted that the sense mass of the proposed device achieved a drive displacement of 4.1μm when a sinusoidal voltage of 0.5V is applied at 1.77 kHz exhibiting a mechanical sensitivity of 1.7μm /°/s in vacuum. The wide bandwidth frequency response of the 2-DoF drive mode oscillator consists of two resonant peaks and a flat region of 2.11 kHz between the peaks defining the operational frequency region. The sense mode resonant frequency can lie anywhere within this region and therefore the amplitude of the response is insensitive to structural parameter variations, enhancing device robustness against such variations. The proposed device has a size of 2.2 × 2.6 mm(2), almost one third in comparison with existing M-DoF vibratory gyroscope with an estimated power consumption of 0.26 Watts. These predicted results illustrate that the chevron-shaped thermal actuator

  5. Thermal Actuation Based 3-DoF Non-Resonant Microgyroscope Using MetalMUMPs

    Directory of Open Access Journals (Sweden)

    Muhammad Masood ul Hassan

    2009-04-01

    Full Text Available High force, large displacement and low voltage consumption are a primary concern for microgyroscopes. The chevron-shaped thermal actuators are unique in terms of high force generation combined with the large displacements at a low operating voltage in comparison with traditional electrostatic actuators. A Nickel based 3-DoF micromachined gyroscope comprising 2-DoF drive mode and 1-DoF sense mode oscillator utilizing the chevron-shaped thermal actuators is presented here. Analytical derivations and finite element simulations are carried out to predict the performance of the proposed device using the thermo-physical properties of electroplated nickel. The device sensitivity is improved by utilizing the dynamical amplification of the oscillation in 2-DoF drive mode using an active-passive mass configuration. A comprehensive theoretical description, dynamics and mechanical design considerations of the proposed gyroscopes model are discussed in detail. Parametric optimization of gyroscope, its prototype modeling and fabrication using MetalMUMPs has also been investigated. Dynamic transient simulation results predicted that the sense mass of the proposed device achieved a drive displacement of 4.1µm when a sinusoidal voltage of 0.5V is applied at 1.77 kHz exhibiting a mechanical sensitivity of 1.7μm /o/s in vacuum. The wide bandwidth frequency response of the 2-DoF drive mode oscillator consists of two resonant peaks and a flat region of 2.11 kHz between the peaks defining the operational frequency region. The sense mode resonant frequency can lie anywhere within this region and therefore the amplitude of the response is insensitive to structural parameter variations, enhancing device robustness against such variations. The proposed device has a size of 2.2 x 2.6 mm2, almost one third in comparison with existing M-DoF vibratory gyroscope with an estimated power consumption of 0.26 Watts. These predicted results illustrate that the chevron

  6. 冻干乙型脑炎减毒活疫苗非动物源性稳定剂的配方及其缓冲液的筛选%Screening of formula and buffer in non-animal-derived stabilizer of freeze-dried live attenuated Japanese encephalitis vaccine

    Institute of Scientific and Technical Information of China (English)

    段凯; 李黎

    2012-01-01

    Objective To screen the formula and buffer in non-animal-derived stabilizer of freeze-dried live attenuated Japanese encephalitis (JE) vaccine. Methods Final bulk and final product of freeze-dried live attenuated JE vaccine were prepared by various formula consisting of dextran-70, sucrose, sorbitol, lactose and histidine dissolved in 0. 01 mol/L PBS and Earles solu-tion respectively, and evaluated for stabilities after storage at various temperatures for various days. The disintegration temperatures (Tc) of the vaccine containing stabilizers of various formula were measured. Results The stabilities of final bulk of JE vaccine con-taining stabilizers of twelve formula were maintained after storage at 4℃ for one week. However, the titer of final bulk showed no sig-nificant change within 3 d after storage at 25℃, and decreased remarkably afterwards. The Tc of vaccine containing stabilizer using 0. 01 mol/L PBS as buffer was lower than that using Earles solution. The titers of final product of freeze-dried live attenuated JE vac-cines containing the stabilizers of formula D2 and F2 using Earles solution as buffer were more than 5. 7 log PFU / ml after storage at 4 and 37℃ for one week. Conclusion The stabilizer consisting of dextran-70, sucrose, sorbitol, lactose and histidine using Earles solu-tion as buffer was suitable for freeze-dried live attenuated JE vaccine.%目的 筛选冻干乙型脑炎减毒活疫苗非动物源性稳定剂的配方及其缓冲液.方法 分别以0.01 mol/L PBS和Earles液为缓冲液,右旋糖苷-70、蔗糖、山梨醇、乳糖及组氨酸不同组合构成的冻干稳定剂,制备乙型脑炎减毒活疫苗半成品及冻干疫苗成品,观察在不同温度存放不同时间的稳定性,并检测不同配方冻干稳定剂的崩解温度(Tc).结果 12种配方冻干稳定剂制成的疫苗半成品可在4℃ 1周内保持滴度稳定性,在25℃3d内保持滴度无明显变化,3d后滴度大幅下降;以0.01 mol/L PBS为缓冲

  7. Immunity of Live Attenuated Japanese Encephalitis(JE)Vaccine to DifferentWild JE Virus Strains%流行性乙型脑炎减毒活疫苗国内外不同野毒株的免疫性

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    目的 研究乙型脑炎减毒活疫苗对国内外不同野毒株的免疫原性。方法 用小鼠保护力试验和空斑减少中和试验检测该疫苗对国内外不同野毒株攻击的保护作用及其免疫血清的中和能力。结果 小鼠免疫1针后均能抵抗国内11株和国外11株乙脑病毒的攻击,保护率均可达90%以上;人体免疫血清对台湾1株和国外9株病毒均有明显的中和作用。结论 SA14-142株乙脑活疫苗具有广谱的免疫原性。%Objective To study on the immunity of live attenuated Japanese Encephalitis(JE)vaccine todifferent wild JE virus strains. Methods The neutralizing effect of the vaccine on different wild JE virusstrains was detected by plaque reduction neutralization test(PRNT), and the immunogenicity of it was studiedin mice by vaccination-challenge protection test. Results The vaccine could protect mice against the challengewith 11 JE vires strains isolated in China and 11 in Thailand,Viemam, Indonesia, India, Phihppines and Ja-pan. The protective rate of it reached above 90%. Human immune sera showed significant neutralizing effect on1 JE virus swain isolated in Taiwan and 9 strains isolated abroad. Conclusion Live attenuated JE vaccine pre-pared with strain SA14-14-2 has broad specmun immunogenicity.

  8. Development of an attenuated live vaccine against highly pathogenic porcine reproductive and respiratory syndrome%高致病性猪繁殖与呼吸综合征活疫苗的研制

    Institute of Scientific and Technical Information of China (English)

    冷雪; 李真光; 夏铭崎; 和彦良; 武华

    2011-01-01

    将高致病性猪繁殖与呼吸综合征病毒致弱株TJM株与耐热冻干保护剂混合制备弱毒活疫苗,并对该活疫苗进行安全性、免疫保护效果和保存期试验。结果显示,4~5周龄仔猪接种该疫苗后体温正常,无任何临床可见异常。该疫苗接种猪对强毒攻击的保护率达4/5以上;将其置于2~8℃保存24个月,病毒效价降低不超过100.5 TCID50/mL。表明该疫苗对猪安全,免疫保护效果良好,且便于保存。%An attenuated highly pathogenic porcine reproductive and respiratory syndrome virus(HP-PRRSV) vaccine was developed by blending the attenuated HP-PRRSV TJM strain with heat endurable protective agent.The safety and efficacy(immunogenicity) in host animals and the period of validity at 2 to 8℃ of the vaccine were tested. In order to test the safety of the vaccine,4 to 5 weeks-old pigs were inoculated with 2mL(106.7TCID50/mL) of the vaccine.In the efficacy study,4 to 5 weeks-old pigs were vaccinated with 1mL of 105.0TCID50 of the vaccine. The animals were challenged with virulent virus on day 28 post-vaccination. To determine the period of validity,the vaccine was sampled on month 3,6,9,12,18,21,and 24 post-vaccination at 2 to 8℃ to test the virus titer. Results revealed that the pigs did not show any clinical diseases post-vaccination.Immunogenicity study demonstrated that the vaccine provided at least four fifths protection to pigs against the HP-PRRSV infection and clinical diseases caused by the challenge.The virus titer decreased no more than 100.5TCID50/mL after 24 month at 2 to 8℃. The results indicated that the vaccine is safe,efficacy to host animals,and easy to be reserved.

  9. Modulation of systemic and mucosal immunity against an inactivated vaccine of Newcastle disease virus by oral co-administration of live attenuated Salmonella enterica serovar Typhimurium expressing chicken interleukin-18 and interferon-α.

    Science.gov (United States)

    Rahman, Md Masudur; Uyangaa, Erdenebelig; Han, Young Woo; Hur, Jin; Park, Sang-Youel; Lee, John Hwa; Kim, Koanhoi; Eo, Seong Kug

    2015-04-01

    Newcastle disease (ND) is a highly contagious disease of chickens causing significant economic losses worldwide. Due to limitations in the efficacy against currently circulating ND viruses, existing vaccination strategies require improvements, and incorporating immunomodulatory cytokines with existing vaccines might be a novel approach. Here, we investigated the systemic and mucosal immunomodulatory properties of oral co-administration of chicken interleukin-18 (chIL-18) and chicken interferon-α (chIFN-α) using attenuated Salmonella enterica serovar Typhimurium on an inactivated ND vaccine. Our results demonstrate that oral administration of S. enterica serovar Typhimurium expressing chIL-18 or chIFN-α provided enhanced systemic and mucosal immune responses, as determined by serum hemagglutination inhibition antibody and NDV Ag-specific IgG as well as NDV Ag-specific IgA in lung and duodenal lavages of chickens immunized with inactivated ND vaccine via the intramuscular or intranasal route. Notably, combined oral administration of S. enterica serovar Typhimurium expressing chIL-18 and chIFN-α significantly enhanced systemic and mucosal immunity in ND-vaccinated chickens, compared to single administration of S. enterica serovar Typhimurium expressing chIL-18 or chIFN-α. In addition, oral co-administration of S. enterica serovar Typhimurium expressing chIL-18 and chIFN-α provided enhanced NDV Ag-specific proliferation of peripheral blood mononuclear cells and Th1-biased cell-mediated immunity, compared to single administration of either construct. Therefore, our results provide valuable insight into the modulation of systemic and mucosal immunity by incorporation of immunomodulatory chIL-18 and chIFN-α using Salmonella vaccines into existing ND vaccines.

  10. Considerable decrease of antibody titers against measles, mumps, and rubella in preschool children from an e-waste recycling area.

    Science.gov (United States)

    Lin, Yucong; Xu, Xijin; Dai, Yifeng; Zhang, Yuling; Li, Weiqiu; Huo, Xia

    2016-12-15

    Data on vaccination effects in children chronically exposed to heavy metals are extremely scarce. This study aims to investigate the immune responsiveness to measles, mumps, and rubella (MMR) vaccination in children from an e-waste recycling area. 378 healthy children from Guiyu (exposed group) and Haojiang (reference group) were surveyed. Blood lead (Pb) levels were measured by graphite furnace atomic absorption. Titers of antibodies against MMR were quantified by ELISA. Blood Pb levels of children from the exposed group were significantly higher than those from the reference group (5.61μg/dL vs. 3.57μg/dL, pe-waste recycling area should be modified.

  11. A case study of a graphical misrepresentation: drawing the wrong conclusions about the measles, mumps and rubella virus vaccine.

    Science.gov (United States)

    Cox, Anthony R; Kirkham, Harold

    2007-01-01

    Graphs have been used in attempts to show a relationship between the measles, mumps and rubella virus (MMR) vaccine and autism. We examine the topic of graphical representation of data in general, and one of these graphs in particular: the one that appeared in a 1999 letter to The Lancet. That graph combined data from England and from California, USA. The author alleged that this graph illustrated a rise in autism rates linked to the use of the MMR vaccine. By examining the presentation closely, we are able to show how this graph misrepresented the data used. We give advice for both authors and publishers in the use of such graphical treatments of data.

  12. Two-layer radio frequency MEMS fractal capacitors in PolyMUMPS for S-band applications

    KAUST Repository

    Elshurafa, Amro M.

    2012-07-23

    In this Letter, the authors fabricate for the first time MEMS fractal capacitors possessing two layers and compare their performance characteristics with the conventional parallel-plate capacitor and previously reported state-of-the-art single-layer MEMS fractal capacitors. Explicitly, a capacitor with a woven structure and another with an interleaved configuration were fabricated in the standard PolyMUMPS surface micromachining process and tested at S-band frequencies. The self-resonant frequencies of the fabricated capacitors were close to 10GHz, which is better than that of the parallel-plate capacitor, which measured only 5.5GHz. Further, the presented capacitors provided a higher capacitance when compared with the state-of-the-art-reported MEMS fractal capacitors created using a single layer at the expense of a lower quality factor. © 2012 The Institution of Engineering and Technology.

  13. Is there a 'regressive phenotype' of Autism Spectrum Disorder associated with the measles-mumps-rubella vaccine? A CPEA Study.

    Science.gov (United States)

    Richler, Jennifer; Luyster, Rhiannon; Risi, Susan; Hsu, Wan-Ling; Dawson, Geraldine; Bernier, Raphael; Dunn, Michelle; Hepburn, Susan; Hyman, Susan L; McMahon, William M; Goudie-Nice, Julie; Minshew, Nancy; Rogers, Sally; Sigman, Marian; Spence, M Anne; Goldberg, Wendy A; Tager-Flusberg, Helen; Volkmar, Fred R; Lord, Catherine

    2006-04-01

    A multi-site study of 351 children with Autism Spectrum Disorders (ASD) and 31 typically developing children used caregiver interviews to describe the children's early acquisition and loss of social-communication milestones. For the majority of children with ASD who had experienced a regression, pre-loss development was clearly atypical. Children who had lost skills also showed slightly poorer outcomes in verbal IQ and social reciprocity, a later mean age of onset of autistic symptoms, and more gastrointestinal symptoms than children with ASD and no regression. There was no evidence that onset of autistic symptoms or of regression was related to measles-mumps-rubella vaccination. The implications of these findings for the existence of a 'regressive phenotype' of ASD are discussed.

  14. INTRALESIONAL MEASLES, MUMPS AND RUBELLA (MMR VACCINE-AN EFFECTIVE THERAPEUTIC TOOL IN THE TREATMENT OF WART

    Directory of Open Access Journals (Sweden)

    Raju

    2015-11-01

    Full Text Available BACKGROUND: Warts are common cutaneous viral infection. Various therapeutic modalities have been using in treatment of wart, but none of them are standardised. Immunotherapy is new current approach in the treatment of wart. AIMS: To know the efficacy and safety profile of Measles Mumps Rubella (MMR Vaccine in the treatment of wart. METHODS: MMR vaccine was injected into a largest single wart intralesionally and subsequent injections given every 2 weeks apart for about 3 to 5 times. Every month followup of patients was done to know the clearance of wart. RESULTS: Complete remission of warts seen in 70.4% of patients, partial remission seen in 22.2% and no response was seen in 7.4% of patients. No serious adverse side effects were seen in the current study. CONCLUSION: MMR vaccine can be considered as a safe, effective, inexpensive intralesional immunotherapeutic modality in the treatment of wart.

  15. Vacinas contra varicela e vacina quádrupla viral Varicella vaccines and measles, mumps, rubella, and varicella vaccine

    Directory of Open Access Journals (Sweden)

    Lucia Ferro Bricks

    2006-07-01

    Full Text Available OBJETIVOS: Apresentar uma revisão atualizada sobre os estudos de eficácia, eventos adversos e esquema vacinal da vacina contra varicela e a nova apresentação combinada com a vacina contra sarampo, caxumba e rubéola. FONTES DOS DADOS: Revisão bibliográfica utilizando a base de dados MEDLINE e LILACS no período de 1999 a 2006. SÍNTESE DOS DADOS: A vacina contra varicela tem uma eficácia entre 70 a 90% contra a infecção e 95 a 98% de proteção contra as formas graves. É uma vacina bem tolerada e pouco reatogênica. Após o seu licenciamento, foram comprovados apenas três casos de transmissão do vírus vacinal de pessoas previamente saudáveis para contatos domiciliares, que desenvolveram doença leve. Apesar das evidências de que a proteção conferida pela vacina pode diminuir com o passar dos anos, ainda não é possível afirmar que seja necessário, no momento, a aplicação de uma segunda dose, tendo em vista a exposição ao vírus selvagem. Após a vacinação universal, as chances de estímulo natural deverão diminuir, e muito provavelmente será necessário a aplicação de doses de reforço. Recentemente foi licenciada a vacina quádrupla viral, um produto combinado com a vacina contra sarampo, caxumba, rubéola e varicela com elevadas taxas de soroconversão. CONCLUSÃO:A vacina contra varicela é recomendada pela Sociedade Brasileira de Pediatria (SBP para as crianças a partir de 1 ano de idade. Esperamos que, em breve, a vacina quádrupla viral esteja disponível no Brasil, pois o uso de vacinas combinadas possibilita uma maior cobertura vacinal.OBJECTIVES: To present an up-to-date review of studies investigating the efficacy, adverse events and vaccination regimens of the varicella vaccine and the new presentation combined with the vaccine for measles, mumps and rubella. SOURCES OF DATA: Bibliographic review of the MEDLINE and LILACS databases covering the period 1999 to 2006 SUMMARY OF THE FINDINGS: The varicella

  16. Landing gear noise attenuation

    Science.gov (United States)

    Moe, Jeffrey W. (Inventor); Whitmire, Julia (Inventor); Kwan, Hwa-Wan (Inventor); Abeysinghe, Amal (Inventor)

    2011-01-01

    A landing gear noise attenuator mitigates noise generated by airframe deployable landing gear. The noise attenuator can have a first position when the landing gear is in its deployed or down position, and a second position when the landing gear is in its up or stowed position. The noise attenuator may be an inflatable fairing that does not compromise limited space constraints associated with landing gear retraction and stowage. A truck fairing mounted under a truck beam can have a compliant edge to allow for non-destructive impingement of a deflected fire during certain conditions.

  17. Risk of febrile seizure after measles-mumps-rubella-varicella vaccine: A systematic review and meta-analysis.

    Science.gov (United States)

    Ma, Shu-Juan; Xiong, Yi-Quan; Jiang, Li-Na; Chen, Qing

    2015-07-17

    Considering the febrile seizure rate, there is no longer a clear preference for use of measles-mumps-rubella-varicella (MMRV) vaccine over separate measles-mumps-rubella (MMR) and varicella (V) vaccine. This work was undertaken to assess the risk of febrile seizure after MMRV vaccine in children. We searched PubMed, Embase, BIOSIS Previews, Scopus, Web of Science, Cochrane Library and other databases through 12 December 2014. Meta-analysis was conducted using R version 3.1.2 and Stata version 12.0. A total of thirty-nine studies were included. Thirty-one published or unpublished clinical trials involving about 40,000 subjects did not show significant differences in incidence of febrile seizure or vaccine related febrile seizure between MMRV and MMR with or without varicella vaccine after any doses, in the risk windows of 0-28, 0-42 or 0-56 days and 7-10 days. In addition, these studies showed that the receipt of concomitant use of MMRV and other pediatric vaccines was not a significant predictor of febrile seizure. Eight post-marketing observations involving more than 3,200,000 subjects were included. No evidence suggested elevated risk of febrile seizure associated with MMRV vaccine among children aged 4-6 years old during 7-10 days or 0-42 days after vaccination. However, an approximately 2-fold increase in risk of seizure or febrile seizure during 7-10 days or 5-12 days after MMRV vaccination was found among children aged 10-24 months, although the highest incidence of seizure was still lower than 2.95‰. First MMRV vaccine dose in children aged 10-24 months was associated with an elevated risk of seizure or febrile seizure. Further post-marketing restudies based on more rigorous study design are needed to confirm the findings. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Seroprevalence of antibodies against measles, rubella, mumps, varicella-zoster, and B. Pertussis in young adults of Madrid, Spain.

    Science.gov (United States)

    González-Escalada, Alba; García-García, Laura; Viguera-Ester, Pablo; Marín-García, Patricia; García, Jesus; Gil-de-Miguel, Angel; Gil-Prieto, Ruth

    2013-09-01

    In recent years, there has been an increase in the number of cases of certain immunopreventable diseases in our country. A high proportion of these have been recorded among the young adult population. The aim of this study was to determine the seroprevalence of antibodies against immunopreventable diseases with the greatest health impacts on the young adult population (19-39 y of age) in Madrid. We collected a total of 1,153 serum samples from healthy volunteers undergoing routine medical visits and used ELISA to determine the presence of IgG antibodies against measles, rubella, mumps, and varicella zoster, as well as Bordetella pertussis. The Pearson's χ(2) test was used to compare prevalences, the Mann-Whitney U test was used to compare means, and the Kruskal-Wallis test was applied for variables with more than 2 categories. Statistical significance was achieved with p values of<0.05. The global prevalence of antibodies was 92.1% for measles, 94.4% for rubella, 88.3% for mumps, 92.8% for varicella zoster, and 70.2% for B. pertussis. No statistically significant differences were found between genders. The prevalence of antibodies against measles was more than 95% in the group of individuals born after 1986, and the percentage of individuals susceptible to rubella was less than 5% in women born after 1986. In spite of adequate vaccination coverage, in our region, a population of young adults exists who have not achieved the objectives of the WHO for the elimination of measles and congenital rubella syndrome.

  19. Intramuscular Immunization of Mice with a Live-Attenuated Triple Mutant of Yersinia pestis CO92 Induces Robust Humoral and Cell-Mediated Immunity To Completely Protect Animals against Pneumonic Plague.

    Science.gov (United States)

    Tiner, Bethany L; Sha, Jian; Ponnusamy, Duraisamy; Baze, Wallace B; Fitts, Eric C; Popov, Vsevolod L; van Lier, Christina J; Erova, Tatiana E; Chopra, Ashok K

    2015-12-01

    Earlier, we showed that the Δlpp ΔmsbB Δail triple mutant of Yersinia pestis CO92 with deleted genes encoding Braun lipoprotein (Lpp), an acyltransferase (MsbB), and the attachment invasion locus (Ail), respectively, was avirulent in a mouse model of pneumonic plague. In this study, we further evaluated the immunogenic potential of the Δlpp ΔmsbB Δail triple mutant and its derivative by different routes of vaccination. Mice were immunized via the subcutaneous (s.c.) or the intramuscular (i.m.) route with two doses (2 × 10(6) CFU/dose) of the above-mentioned triple mutant with 100% survivability of the animals. Upon subsequent pneumonic challenge with 70 to 92 50% lethal doses (LD(50)) of wild-type (WT) strain CO92, all of the mice survived when immunization occurred by the i.m. route. Since Ail has virulence and immunogenic potential, a mutated version of Ail devoid of its virulence properties was created, and the genetically modified ail replaced the native ail gene on the chromosome of the Δlpp ΔmsbB double mutant, creating a Δlpp ΔmsbB::ailL2 vaccine strain. This newly generated mutant was attenuated similarly to the Δlpp ΔmsbB Δail triple mutant when administered by the i.m. route and provided 100% protection to animals against subsequent pneumonic challenge. Not only were the two above-mentioned mutants cleared rapidly from the initial i.m. site of injection in animals with no histopathological lesions, the immunized mice did not exhibit any disease symptoms during immunization or after subsequent exposure to WT CO92. These two mutants triggered balanced Th1- and Th2-based antibody responses and cell-mediated immunity. A substantial increase in interleukin-17 (IL-17) from the T cells of vaccinated mice, a cytokine of the Th17 cells, further augmented their vaccine potential. Thus, the Δlpp ΔmsbB Δail and Δlpp ΔmsbB::ailL2 mutants represent excellent vaccine candidates for plague, with the latter mutant still retaining Ail immunogenicity but

  20. Living Technology

    DEFF Research Database (Denmark)

    2010-01-01

    This book is aimed at anyone who is interested in learning more about living technology, whether coming from business, the government, policy centers, academia, or anywhere else. Its purpose is to help people to learn what living technology is, what it might develop into, and how it might impact...... our lives. The phrase 'living technology' was coined to refer to technology that is alive as well as technology that is useful because it shares the fundamental properties of living systems. In particular, the invention of this phrase was called for to describe the trend of our technology becoming...... increasingly life-like or literally alive. Still, the phrase has different interpretations depending on how one views what life is. This book presents nineteen perspectives on living technology. Taken together, the interviews convey the collective wisdom on living technology's power and promise, as well as its...

  1. Living Technology

    DEFF Research Database (Denmark)

    2010-01-01

    This book is aimed at anyone who is interested in learning more about living technology, whether coming from business, the government, policy centers, academia, or anywhere else. Its purpose is to help people to learn what living technology is, what it might develop into, and how it might impact...... our lives. The phrase 'living technology' was coined to refer to technology that is alive as well as technology that is useful because it shares the fundamental properties of living systems. In particular, the invention of this phrase was called for to describe the trend of our technology becoming...... increasingly life-like or literally alive. Still, the phrase has different interpretations depending on how one views what life is. This book presents nineteen perspectives on living technology. Taken together, the interviews convey the collective wisdom on living technology's power and promise, as well as its...

  2. Combination Measles-Mumps-Rubella-Varicella Vaccine in Healthy Children: A Systematic Review and Meta-analysis of Immunogenicity and Safety.

    Science.gov (United States)

    Ma, Shu-Juan; Li, Xing; Xiong, Yi-Quan; Yao, A-Ling; Chen, Qing

    2015-11-01

    A combined measles-mumps-rubella-varicella (MMRV) vaccine is expected to facilitate universal immunization against these 4 diseases. This study was undertaken to synthesize current research findings of the immunogenicity and safety of MMRV in healthy children.We searched PubMed, Embase, BIOSIS Previews, Web of Science, Cochrane Library, and other databases through September 9, 2014. Eligible randomized controlled trials (RCTs) were selected and collected independently by 2 reviewers. Meta-analysis was conducted using Stata 12.0 and RevMan 5.3.Twenty-four RCTs were included in qualitative synthesis. Nineteen RCTs compared single MMRV dose with measles-mumps-rubella vaccine with or without varicella vaccine (MMR + V/MMR). Similar seroconversion rates of these 4 viruses were found between comparison groups. There were comparable geometric mean titers (GMTs) against mumps and varicella viruses between MMRV group and MMR + V/MMR group. MMRV group achieved enhanced immune response to measles component, with GMT ratio of 1.66 (95% confidence interval [CI] 1.48, 1.86; P measles/rubella-like rash (relative risks 1.44-1.45) in MMRV groups.MMRV had comparable immunogenicity and overall safety profiles to MMR + V/MMR in healthy children based on current evidence.

  3. When, and how, should we introduce a combination measles-mumps-rubella (MMR) vaccine into the national childhood expanded immunization programme in South Africa?

    Science.gov (United States)

    Cameron, Neil A

    2012-09-07

    This article briefly reviews the history and epidemiology of measles, mumps and rubella disease and the case for introducing combination measles-mumps-rubella (MMR) vaccine into the national childhood immunization schedule in South Africa. Despite adopting the World Health Organization's Measles Elimination strategy in 1996 and achieving a significant decrease the incidence of measles, added effort is needed in South and southern Africa to reach the goal to eliminate endogenous spread measles. Mumps is still common disease of childhood and while there are few sequelae, even the rare complications are important in large populations. Congenital rubella syndrome is seldom reported, but it is estimated that of the million or so children born every year in South Africa over 600 infants are affected to some degree by rubella infection. The naturally acquired immunity to rubella in women of childbearing age in South Africa has been estimated at over 90%, so that introducing a rubella containing vaccine in childhood may paradoxically increase the proportion of girls reaching puberty still susceptible to rubella. The elimination of endogenous measles and rubella is being achieved in many countries in South America, and despite the recent measles epidemic, must still be seriously considered for South and southern Africa. Current constraints and potential steps needed to reach the goal in South Africa are discussed.

  4. Effectiveness Assessment of the Supplementary Immunization Activities for Measles Attenuated Live Vaccine in Anhui Province in 2009%安徽省2009年麻疹减毒活疫苗补充免疫活动效果评估

    Institute of Scientific and Technical Information of China (English)

    戴智勤; 唐继海; 张伟青; 易厦晖; 刘丹青; 何纳

    2012-01-01

    目的 对安徽省2009年麻疹减毒活疫苗(Measles Attenuated Live Vaccine,MV)补充免疫活动(Supplementary Immunization Activities,SIA)的流行病学效果进行评估,为消除麻疹提供参考.方法