Vidor, J D; Jean-Denis, Shu
The inactivated poliovirus vaccine (IPV) is a very old tool in the fight against poliomyelitis. Though supplanted by oral poliovirus vaccine (OPV) in the 1960s and 1970s, the IPV has now become an inevitable choice because of the increasingly recognized risks associated with continuous use of OPVs. Following the pioneering work of Jonas Salk, who established key principles for the IPV, considerable experience has accumulated over the years. This work has led to modern Salk IPV-containing vaccines, based on the use of inactivated wildtype polioviruses, which have been deployed for routine use in many countries. Very good protection against paralysis is achieved with IPV through the presence of circulating antibodies able to neutralize virus infectivity toward motor neurons. In addition, with IPV, a variable degree of protection against mucosal infection (and therefore transmission) through mucosal antibodies and immune cells is achieved, depending on previous exposure of subjects to wildtype or vaccine polioviruses. The use of an IPV-followed-by-OPV sequential immunization schedule has the potential advantage of eliminating the vaccine-associated paralytic poliomyelitis (VAPP) risk, while limiting the risks of vaccine-derived poliovirus (VDPVs). Sabin strain-derived IPVs are new tools, only recently beginning to be deployed, and data are being generated to document their performance. IPVs will play an irreplaceable role in global eradication of polio.
Martin, J; Daas, A; Milne, C
Inactivated poliomyelitis vaccines are an important part of the World Health Organization (WHO) control strategy to eradicate poliomyelitis. Requirements for the quality control of poliomyelitis vaccines (inactivated) include the use of an in vitro D antigen quantification assay for potency determination on the final lot as outlined in the European Pharmacopoeia (Ph. Eur.) monograph 0214. Performance of this assay requires a reference preparation calibrated in International Units (IU). A Ph. Eur. biological reference preparation (BRP) for poliomyelitis vaccine (inactivated) calibrated in IU has been established for this purpose. Due to the dwindling stocks of batch 2 of the BRP a collaborative study was run as part of the European Directorate for the Quality of Medicines & HealthCare (EDQM) Biological Standardisation Programme to establish BRP batch 3 (BRP3). Twelve laboratories including Official Medicines Control Laboratories (OMCLs) and manufacturers participated. The candidate BRP3 (cBRP3) was from the same source and had the same characteristics as BRP batch 2 (BRP2). During the study the candidate was calibrated against the 3 rd International Standard for inactivated poliomyelitis vaccine using in-house D antigen ELISA assays in line with the Ph. Eur. monograph 0214. The candidate was also compared to BRP2 to evaluate the continuity. Based on the results of the study, values of 320 DU/mL, 78 DU/mL and 288 DU/mL (D antigen units/mL) (IU) for poliovirus type 1, 2 and 3 respectively were assigned to the candidate. In June 2016, the Ph. Eur. Commission adopted the material as Ph. Eur. BRP for poliomyelitis vaccine (inactivated) batch 3.
Bian, Chuan-xiu; Jiang, Shu-de; Yang, Jian-yong; Sun, Ming-bo; Xie, Ming-xue; Zhang, Xin-wen; Liao, Guo-yang; Li, Wei-dong
To investigate the effect of 2-phenoxyethanol on potency of Sabin inactivated poliomyelitis vaccine (IPV). Sabin IPV samples containing 5 mg or 7 mg 2-phenoxyethanol each dosage respectively were placed separately at 4 degrees C, 37 degrees C for 2 days and 7 days. D-antigen contents were tested with ELISA method. Then neutralizing antibodies in mice and guinea pigs were detected. The safety experiment was performed according to unusual toxicity test of China requirement for biological product. After addition of 2-phenoxyethanol, the I, II, and III D-antigen contents of Sabin IPV did not change. The antibody levels in mice and guinea pigs were not different between experimental group and control group. Animals were safe during observation period. 2-Phenoxyethanol had no effect on potency and safety of Sabin IPV. It can be used as antiseptic for Sabin IPV.
Zhao, Dan; Ma, Rui; Zhou, Tao; Yang, Fan; Wu, Jin; Sun, Hao; Liu, Fang; Lu, Li; Li, Xiaomei; Zuo, Shuyan; Yao, Wei; Yin, Jian
When included in a sequential polio vaccination schedule, inactivated polio vaccine (IPV) reduces the risk for vaccine-associated paralytic poliomyelitis (VAPP), a rare adverse event associated with receipt of oral poliovirus vaccine (OPV). During January 2014, the World Health Organization (WHO) recommended introduction of at least 1 IPV dose into routine immunization schedules in OPV-using countries (1). The Polio Eradication and Endgame Strategic Plan 2013-2018 recommended completion of IPV introduction in 2015 and globally synchronized withdrawal of OPV type 2 in 2016 (2). Introduction of 1 dose of IPV into Beijing's Expanded Program on Immunization (EPI) on December 5, 2014 represented China's first province-wide IPV introduction. Coverage with the first dose of polio vaccine was maintained from 96.2% to 96.9%, similar to coverage with the first dose of diphtheria and tetanus toxoids and pertussis vaccine (DTP) (96.5%-97.2%); the polio vaccine dropout rate (the percentage of children who received the first dose of polio vaccine but failed to complete the series) was 1.0% in 2015 and 0.4% in 2016. The use of 3 doses of private-sector IPV per child decreased from 18.1% in 2014, to 17.4% in 2015, and to 14.8% in 2016. No cases of VAPP were identified during 2014-2016. Successful introduction of IPV into the public sector EPI program was attributed to comprehensive planning, preparation, implementation, robust surveillance for adverse events after immunization (AEFI), and monitoring of vaccination coverage. This evaluation provided information that helped contribute to the expansion of IPV use in China and in other OPV-using countries.
Verdijk, Pauline; Rots, Nynke Y; Bakker, Wilfried A M
Following achievement of polio eradication, the routine use of all live-attenuated oral poliovirus vaccines should be discontinued. However, the costs per vaccine dose for the alternative inactivated poliovirus vaccine (IPV) are significantly higher and the current production capacity is not sufficient for worldwide distribution of the vaccine. In order to achieve cost-prize reduction and improve affordability, IPV production processes and dose-sparing strategies should be developed to facilitate local manufacture at a relatively lower cost. The use of attenuated Sabin instead of wild-type polio strains will provide additional safety during vaccine production and permits production in low-cost settings. Sabin-IPV is under development by several manufacturers. This article gives an overview of results from clinical trials with Sabin-IPV and discusses the requirements and challenges in the clinical development of this novel IPV.
Falleiros-Arlant, Luiza Helena; Avila-Agüero, María Luisa; Brea del Castillo, José; Mariño, Cristina
Even though we have already covered 99% of the path to eradicate poliomyelitis from the world, this disease is still causing paralysis in children. Its eradication means not only the end of wild poliovirus circulation, but vaccine-derived poliovirus circulation as well. Taking into account different factors such as: current epidemiological data, adverse events of the attenuated oral poliomyelitis vaccine (OPV), the availability of an injectable inactivated vaccine (IPV) without the potential of causing the severe adverse events of the oral vaccine (OPV), the efficacy and effectiveness of the IPV in several countries of the world where it has been used for several years, the rationale of changing the vaccination schedule in different Latin American countries; the Latin American Society of Pediatric Infectious Diseases (SLIPE) announces its recommendation of switching to IPV in Latin America, by this Declaration, with an Action Plan for 2014-2015 period as regards vaccination against polio policies in Latin America. 1. The optimal proposed schedule consists of four IPV doses (three doses in the primary schedule plus a booster dose), whether IPV is combined or not with other indicated vaccines in the immunization program of the country. During the OPV to IPV transition phase, an alternative schedule is acceptable; 2. Countries should set optimal strategies in order to maintain and improve vaccination coverage, and implement a nominal immunization registry; 3. Improving the Epidemiological Surveillance of Acute Flaccid Paralysis (AFP) and setting up an environmental surveillance program; 4. Setting up strategies for introducing IPV in National Immunization Programs, such as communicating properly with the population, among others; 5. Bringing scientific societies closer to decision makers; 6. Ensuring optimal supply and prices for IPV introduction; 7. Training vaccination teams; 8. Enhancing the distribution and storing logistics of vaccines. In addition to the
Khan, M M; Sharma, S; Tripathi, B; Alvarez, F P
To conduct a budget impact analysis (BIA) of introducing the immunization recommendations of India Expert Advisory Group (IEAG) for the years 2015-2017. The recommendations include introduction of one inactivated poliomyelitis vaccine (IPV) dose in the regular child immunization programme along with reductions in oral polio vaccine (OPV) doses in supplemental programmes. This is a national level analysis of budget impact of new polio immunization recommendations. Since the states of India vary widely in terms of size, vaccine coverage and supplemental vaccine needs, the study estimated the budget impact for each of the states of India separately to derive the national level budget impact. Based on the recommendations of IEAG, the BIA assumes that all children in India will get an IPV dose at 14 weeks of age in addition to the OPV and DPT (or Pentavalent-3) doses. Cost of introducing the IPV dose was estimated by considering vaccine price and vaccine delivery and administration costs. The cost savings associated with the reduction in number of doses of OPV in supplemental immunization were also estimated. The analysis used India-specific or international cost parameters to estimate the budget impact. Introduction of one IPV dose will increase the cost of vaccines in the regular immunization programme from $20 million to $47 million. Since IEAG recommends lower intensity of supplemental OPV vaccination, polio vaccine cost of supplemental programme is expected to decline from $72 million to $53 million. Cost of administering polio vaccines will also decline from $124 million to $105 million mainly due to the significantly lower intensity of supplemental polio vaccination. The net effect of adopting IEAG's recommendations on polio immunization turns out to be cost saving for India, reducing total polio immunization cost by $6 million. Additional savings could be achieved if India adopts the new policy regarding the handling of multi-dose vials after opening
Farizo, Karen M.; And Others
Examines poliomyelitis in the United States by reviewing clinical manifestations and outcomes, history, recent epidemiologic characteristics, characteristics of currently available vaccines, controversies surrounding vaccination policy, current poliovirus vaccination recommendations, and prospects for worldwide eradication. Poliomyelitis remains…
Salk, Jonas; Salk, Darrell
Discusses control of poliomyelitis and influenza by live and killed virus vaccines. Considered are the etiological agents, pathogenic mechanisms and epidemiology of each disease. Reviews recent scientific studies of the diseases. Recommends use of killed virus vaccines in controlling both diseases. (CS)
John, T Jacob
Inactivated poliovirus vaccine (IPV), developed in the USA by Jonas Salk in the early 1950s, was field tested in 1954, and found to be safe and effective. The year 2004 marks the golden jubilee of this breakthrough. From 1955 IPV was used extensively in the US and polio incidence declined by more than 95 per cent. However, in 1962, when oral poliovirus vaccine (OPV) became available, the national policy was shifted to its exclusive use, for reasons other than science and economics. The World Health Organisation (WHO) also adopted the policy of the exclusive use of OPV in developing countries. Thus IPV fell into disrepute in much of the world, while Northern European countries continued to use it. New research led to improving its potency, reducing its manufacturing costs and combining it with the diphtheria-tetanus-pertussis (DTP) vaccine to simplify its administration and reduce programmatic costs. All countries that chose to persist with IPV eliminated poliovirus circulation without OPV-induced polio or the risk of live vaccine viruses reverting to wild-like nature. IPV is highly immunogenic, confers mucosal immunity and exerts herd protective effect, all qualities of a good vaccine. It can be used in harmony with the extendend programme on immunization (EPI) schedule of infant immunisation with DTP, thus reducing programmatic costs. During the last ten years IPV has once again regained its popularity and some 25 industrialised countries use it exclusively. The demand is increasing from other countries and the supply has not caught up, leaving market forces to dictate the sale price of IPV. Anticipating such a turn of events India had launched its own IPV manufacturing programme in 1987, but the project was closed in 1992. Today it is not clear if we can complete the job of global polio eradication without IPV, on account of the genetic instability of OPV and the consequent tendency of vaccine viruses to revert to wild-like properties. The option to use IPV is
Immunogenicity, Safety, and Tolerability of Bivalent rLP2086 Meningococcal Group B Vaccine Administered Concomitantly With Diphtheria, Tetanus, and Acellular Pertussis and Inactivated Poliomyelitis Vaccines to Healthy Adolescents.
Vesikari, Timo; Wysocki, Jacek; Beeslaar, Johannes; Eiden, Joseph; Jiang, Qin; Jansen, Kathrin U; Jones, Thomas R; Harris, Shannon L; O'Neill, Robert E; York, Laura J; Perez, John L
Concomitant administration of bivalent rLP2086 (Trumenba [Pfizer, Inc] and diphtheria, tetanus, and acellular pertussis and inactivated poliovirus vaccine (DTaP/IPV) was immunologically noninferior to DTaP/IPV and saline and was safe and well tolerated. Bivalent rLP2086 elicited robust and broad bactericidal antibody responses to diverse Neisseria meningitidis serogroup B strains expressing antigens heterologous to vaccine antigens after 2 and 3 vaccinations. Bivalent rLP2086, a Neisseria meningitidis serogroup B (MnB) vaccine (Trumenba [Pfizer, Inc]) recently approved in the United States to prevent invasive MnB disease in individuals aged 10-25 years, contains recombinant subfamily A and B factor H binding proteins (fHBPs). This study evaluated the coadministration of Repevax (diphtheria, tetanus, and acellular pertussis and inactivated poliovirus vaccine [DTaP/IPV]) (Sanofi Pasteur MSD, Ltd) and bivalent rLP2086. Healthy adolescents aged ≥11 to B proteins different from the vaccine antigens. Participants were randomly assigned to receive bivalent rLP2086 + DTaP/IPV (n = 373) or saline + DTaP/IPV (n = 376). Immune responses to DTaP/IPV in participants who received bivalent rLP2086 + DTaP/IPV were noninferior to those in participants who received saline + DTaP/IPV.The proportions of bivalent rLP2086 + DTaP/IPV recipients with prespecified seroprotective hSBA titers to the 4 MnB test strains were 55.5%-97.3% after vaccination 2 and 81.5%-100% after vaccination 3. The administration of bivalent rLP2086 was well tolerated and resulted in few serious adverse events. Immune responses to DTaP/IPV administered with bivalent rLP2086 to adolescents were noninferior to DTaP/IPV administered alone. Bivalent rLP2086 was well tolerated and elicited substantial and broad bactericidal responses to diverse MnB strains in a high proportion of recipients after 2 vaccinations, and these responses were further enhanced after 3 vaccinations.ClinicalTrials.gov identifier NCT01323270
Lashkevich, V A
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
The first vaccine against poliovirus (PV), the causative agent of poliomyelitis, was developed in the 1950s by Jonas Salk. The vaccine (IPV) consists of an injected dose of purified and inactivated wild-type PVs (all three serotypes). Soon after this discovery, at the Rijks Instituut voor de
Seĭbil', V B; Malyshkina, L P
Problem of poliomyelitis eradication is examined in the review. After the eradication of wild poliovirus, vaccine poliomyelitis virus continues to circulate in the human population. In rare cases it can cause the development of the disease. The authors describe disadvantages of the use of oral and inactivated poliomyelitis vaccines and note that by using oral poliomyelitis vaccine and eradication only of wild poliovirus, eradication of poliomyelitis as an infection will not succeed. As one of the approaches to reach this goal the authors propose the use of various enterovirus interference. Use of live enterovirus vaccine is described and its advantages and disadvantages are examined.
Full Text Available The present article reports a case involving an immunocompetent, previously well child who, despite two previous doses of inactivated poliovirus vaccine, developed severe flaccid paralysis consistent with polio after receiving oral polio vaccine.
M. L. F. Leal
Full Text Available Different formulations of trivalent oral poliomyelitis vaccine were tested, in order to obtain better thermostability, reduce corrosion of machinery and improve production costs. Magnesium chloride, sucrose, arginine and 199-Hank's medium were used in the formulations. The most appropriate formulation was a mixture of MgCl2 and arginine, which was highly thermostable, and had low production costs. The low corrosive formulation was rejected, due to low thermostability on storage.
... poliomyelitis in most people (immunization is over 90% effective). Alternative Names ... S, Arnold WD. Motor neuron diseases. In: Cifu DX, ed. Braddom's Physical Medicine and Rehabilitation . 5th ed. Philadelphia, PA: Elsevier; 2016: ...
Platt, Lauren R; Estívariz, Concepción F; Sutter, Roland W
Vaccine-associated paralytic poliomyelitis (VAPP) is a rare adverse event associated with oral poliovirus vaccine (OPV). This review summarizes the epidemiology and provides a global burden estimate. A literature review was conducted to abstract the epidemiology and calculate the risk of VAPP. A bootstrap method was applied to calculate global VAPP burden estimates. Trends in VAPP epidemiology varied by country income level. In the low-income country, the majority of cases occurred in individuals who had received >3 doses of OPV (63%), whereas in middle and high-income countries, most cases occurred in recipients after their first OPV dose or unvaccinated contacts (81%). Using all risk estimates, VAPP risk was 4.7 cases per million births (range, 2.4-9.7), leading to a global annual burden estimate of 498 cases (range, 255-1018). If the analysis is limited to estimates from countries that currently use OPV, the VAPP risk is 3.8 cases per million births (range, 2.9-4.7) and a burden of 399 cases (range, 306-490). Because many high-income countries have replaced OPV with inactivated poliovirus vaccine, the VAPP burden is concentrated in lower-income countries. The planned universal introduction of inactivated poliovirus vaccine is likely to substantially decrease the global VAPP burden by 80%-90%. © 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: email@example.com.
Estívariz, Concepción F; Molnár, Zsuzsanna; Venczel, Linda; Kapusinszky, Beatrix; Zingeser, James A; Lipskaya, Galina Y; Kew, Olen M; Berencsi, György; Csohán, Agnes
Historical records of patients with vaccine-associated paralytic poliomyelitis (VAPP) in Hungary during 1961-1981 were reviewed to assess the risk of VAPP after oral polio vaccine (OPV) administration. A confirmed VAPP case was defined as a diagnosis of paralytic poliomyelitis and residual paralysis at 60 days in a patient with an epidemiologic link to the vaccine. Archived poliovirus isolates were retested using polymerase chain reaction and sequencing of the viral protein 1 capsid region. This review confirmed 46 of 47 cases previously reported as VAPP. Three cases originally linked to monovalent OPV (mOPV) 3 and one case linked to mOPV1 presented after administration of bivalent OPV 1 + 3 (bOPV). The adjusted VAPP risk per million doses administered was 0.18 for mOPV1 (2 cases/11.13 million doses), 2.96 for mOPV3 (32 cases/10.81 million doses), and 12.82 for bOPV (5 cases/390,000 doses). Absence of protection from immunization with inactivated poliovirus vaccine or exposure to OPV virus from routine immunization and recent injections could explain the higher relative risk of VAPP in Hungarian children. In polio-endemic areas in which mOPV3 and bOPV are needed to achieve eradication, the higher risk of VAPP would be offset by the high risk of paralysis due to wild poliovirus and higher per-dose efficacy of mOPV3 and bOPV compared with trivalent OPV.
Bencskó, G; Ferenci, T
Recent polio outbreaks in Syria and Ukraine, and isolation of poliovirus from asymptomatic carriers in Israel have raised concerns that polio might endanger Europe. We devised a model to calculate the time needed to detect the first case should the disease be imported into Europe, taking the effect of vaccine coverage - both from inactivated and oral polio vaccines, also considering their differences - on the length of silent transmission into account by deriving an 'effective' case/infection ratio that is applicable for vaccinated populations. Using vaccine coverage data and the newly developed model, the relationship between this ratio and vaccine coverage is derived theoretically and is also numerically determined for European countries. This shows that unnoticed transmission is longer for countries with higher vaccine coverage and a higher proportion of IPV-vaccinated individuals among those vaccinated. Assuming borderline transmission (R = 1·1), the expected time to detect the first case is between 326 days and 512 days in different countries, with the number of infected individuals between 235 and 1439. Imperfect surveillance further increases these numbers, especially the number of infected until detection. While longer silent transmission does not increase the number of clinical diseases, it can make the application of traditional outbreak response methods more complicated, among others.
This podcast describes paralytic poliomyelitis infections acquired by immune-deficient Iranian children following their exposure to live-virus polio vaccine. Olen Kew, Associate Director for Global Laboratory Science at CDC, discusses implications of the use of live-virus vaccines in global polio eradication efforts.
Full Text Available In the year 1988, World Health Organization (WHO claims that polio viruses should be eradicated after year 2000. However, until year 2010 the world have not been free from polio viruses circulation. So many effort had been achieved and it is estimated that the world will be free from polio virus after the year 2013. Control of poliomyelitis in Indonesia has been commenced since 1982 with routine immunization of polio program and the National Immunization Days (NID has been commenced since 1995,1996,2005 and 2006. When the world is free from polio virus, WHO suggests several alternative effort to maintain the world free from polio viruses : I stop the OPV (Oral Polio Vaccine and no polio immunization, 2 stop OPV and stock pile mOPV (monovalent OPV, 3 use OPV and IPV (Inactivated Polio Vaccine in a certain times, 4 use IPV only in a certain times. IPV has been used routinely in develop countries but has not been used in the developing countries. Several studies in development countries has been conducted, but had not been done in the developing countries. Indonesia collaboration with WHO has conducted the study of IPV in Yogyakarta Province since year 2002 until year 2010. The overall aim of the study is to compile the necessary data that will inform global and national decision-making regarding future polio immunization policies for the OPV cessation era. The data generated from the study will be particularly important to make decisions regarding optimal IPV use in developing tropical countries. It is unlikely that this data can be assembled through other means than through this study. The tentative result of the study shows that OPV immunization coverage in the year 2004 is 99% in four district and 93 % in the Yogyakarta city. Environment surveillance shows that there are 65.7% polio virus detected from 137 sewage samples pre IPV swich, and 4.8% polio virus detected from 83 sewage samples post IPV swich. Survey polio antibody serologis shows
This podcast describes paralytic poliomyelitis infections acquired by immune-deficient Iranian children following their exposure to live-virus polio vaccine. Olen Kew, Associate Director for Global Laboratory Science at CDC, discusses implications of the use of live-virus vaccines in global polio eradication efforts. Created: 7/6/2010 by National Center for Emerging and Zoonotic Infectious Diseases, National Center for Immunization and Respiratory Diseases. Date Released: 7/6/2010.
O'Reilly, Kathleen M; Lamoureux, Christine; Molodecky, Natalie A; Lyons, Hil; Grassly, Nicholas C; Tallis, Graham
The international spread of wild poliomyelitis outbreaks continues to threaten eradication of poliomyelitis and in 2014 a public health emergency of international concern was declared. Here we describe a risk scoring system that has been used to assess country-level risks of wild poliomyelitis outbreaks, to inform prioritisation of mass vaccination planning, and describe the change in risk from 2014 to 2016. The methods were also used to assess the risk of emergence of vaccine-derived poliomyelitis outbreaks. Potential explanatory variables were tested against the reported outbreaks of wild poliomyelitis since 2003 using multivariable regression analysis. The regression analysis was translated to a risk score and used to classify countries as Low, Medium, Medium High and High risk, based on the predictive ability of the score. Indicators of population immunity, population displacement and diarrhoeal disease were associated with an increased risk of both wild and vaccine-derived outbreaks. High migration from countries with wild cases was associated with wild outbreaks. High birth numbers were associated with an increased risk of vaccine-derived outbreaks. Use of the scoring system is a transparent and rapid approach to assess country risk of wild and vaccine-derived poliomyelitis outbreaks. Since 2008 there has been a steep reduction in the number of wild poliomyelitis outbreaks and the reduction in countries classified as High and Medium High risk has reflected this. The risk of vaccine-derived poliomyelitis outbreaks has varied geographically. These findings highlight that many countries remain susceptible to poliomyelitis outbreaks and maintenance or improvement in routine immunisation is vital.
Immunogenicity and safety of one dose of diphtheria, tetanus, acellular pertussis and poliomyelitis vaccine (Repevax®) followed by two doses of diphtheria, tetanus and poliomyelitis vaccine (Revaxis®) in adults aged ≥ 40 years not receiving a diphtheria- and tetanus-containing vaccination in the last 20 years.
Dominicus, Rolf; Galtier, Florence; Richard, Patrick; Baudin, Martine
The immunogenicity and safety of one dose of Tdap-IPV (tetanus, diphtheria, acellular pertussis and inactivated poliomyelitis vaccine) and two doses of Td-IPV (tetanus, diphtheria and inactivated poliomyelitis vaccine) were assessed in adults who had not received a diphtheria- and tetanus-containing vaccine in the last 20 years. This open-label, multicentre study was conducted in adults aged ≥ 40 years with no diphtheria- and tetanus-containing vaccine in the last 20 years. Participants received one dose of Tdap-IPV followed by two doses of Td-IPV (0, 1, 6 month schedule). Primary immunogenicity objectives: to demonstrate acceptable seroprotection rates (percentage of participants with antibody titre above threshold) post-dose 3 for diphtheria (≥ 0.1IU/mL by seroneutralization assay [SNA]); tetanus (≥ 0.1IU/mL by enzyme-linked immunosorbent assay [ELISA]); and poliomyelitis (≥ 8 1/dil by SNA); and to evaluate the percentage of participants with an antibody concentration ≥ 5EU/mL (by ELISA) for pertussis antigens post-dose 1. Seroprotection rates were acceptable if the lower limit of the 95% confidence interval (CI) was >95%. Percentage of participants with basic clinical immunity against diphtheria (≥ 0.01IU/mL) was also assessed. Safety (adverse events [AEs] and serious AEs) was assessed after each dose. Overall, 336 participants were included (mean age: 60.2 years). Post-dose 3 seroprotection rates were: diphtheria, 94.6% (CI 91.5-96.8); tetanus and poliomyelitis, 100% (CI: 98.8-100). Percentage of participants with an antibody titre ≥ 5EU/mL against pertussis antigens was ≥ 95.8% for all five pertussis components. Basic clinical immunity against diphtheria was achieved in 100% (CI: 98.8-100) of participants. AEs were reported more frequently following vaccination with Tdap-IPV (post-dose 1: 65.3%) than with Td-IPV (post-dose 2: 48.3%; post-dose 3: 50.3%). This study highlights the benefits of using Tdap-IPV followed by two doses of Td-IPV in an
Delpeyroux, Francis; Colbère-Garapin, Florence; Razafindratsimandresy, Richter; Sadeuh-Mba, Serge; Joffret, Marie-Line; Rousset, Dominique; Blondel, Bruno
The oral poliovaccine, a live vaccine made of attenuated poliovirus strains, is the main tool of the vaccination campaigns organised for eradicating poliomyelitis. these campaigns had led to the decline and, thereafter, to the disappearance of wild poliovirus strains of the three serotypes (1-3) in most parts of the world. However, when the poliovaccine coverage becomes too low, vaccine polioviruses can circulate in insufficiently immunized populations and become then pathogenic by mutations and genetic recombination with other enteroviruses of the same species, in particular some coxsackievirus A. These mutated and recombinant vaccine strains have been implicated in several epidemics of paralytic poliomyelitis. Two polio outbreaks associated with these pathogenic circulating vaccine-derived poliovirus (cVDPV) occurred in 2001-2002 and 2005 in the South of Madagascar where vaccine coverage was low. These cVDPV, of serotype 2 or 3, were isolated from paralyzed children and some of their healthy contacts. Other cVDPV were isolated in the same region from healthy children in 2011, indicating that these viruses were circulating again. Vaccination campaigns could stop the outbreaks in 2002 and 2005, and most probably prevent another one in 2011. Therefore, the genetic plasticity of poliovaccine strains that threatens the benefit of vaccination campaigns is the target of an accurate surveillance and an important theme of studies in the virology laboratories of the Institut Pasteur international network. © 2013 médecine/sciences – Inserm.
Safety and reactogenicity of the combined diphtheria-tetanus-acellular pertussis-inactivated poliovirus-Haemophilus influenzae type b (DTPa-IPV/Hib) vaccine in healthy Vietnamese toddlers: An open-label, phase III study.
Anh, Dang Duc; Van Der Meeren, Olivier; Karkada, Naveen; Assudani, Deepak; Yu, Ta-Wen; Han, Htay Htay
The introduction of combination vaccines plays a significant role in increasing vaccine acceptance and widening vaccine coverage. Primary vaccination against diphtheria, tetanus, pertussis, poliomyelitis and Haemophilus influenza type b (Hib) diseases has been implemented in Vietnam. In this study we evaluated the safety and reactogenicity of combined diphtheria-tetanus-pertussis-inactivated polio (DTPa-IPV)/Hib vaccine when administered as a booster dose in 300 healthy Vietnamese children Vietnamese children aged <2 years.
Shirato, Haruko; Someya, Yuichi; Ochiai, Masaki; Horiuchi, Yoshinobu; Takahashi, Motohide; Takeda, Naokazu; Wakabayashi, Kengo; Ouchi, Yasumitsu; Ota, Yoshihiro; Tano, Yoshio; Abe, Shinobu; Yamazaki, Shudo; Wakita, Takaji
As one aspect of its campaign to eradicate poliomyelitis, the World Health Organization (WHO) has encouraged development of the inactivated polio vaccine (IPV) derived from the Sabin strains (sIPV) as an option for an affordable polio vaccine, especially in low-income countries. The Japan Poliomyelitis Research Institute (JPRI) inactivated three serotypes of the Sabin strains and made sIPV preparations, including serotypes 1, 2 and 3 D-antigens in the ratio of 3:100:100. The National Institute of Infectious Diseases, Japan, assessed the immunogenic stability of these sIPV preparations in a rat potency test, according to an evaluation method recommended by the WHO. The immunogenicity of the three serotypes was maintained for at least 4 years when properly stored under -70°C. Based on these data, the sIPV preparations made by JPRI have been approved as national reference vaccines by the Japanese national control authority and used for the quality control of the tetracomponent sIPV-containing diphtheria-tetanus-acellular pertussis combination vaccines that were licensed for a routine polio immunization in Japan. Copyright © 2014 Elsevier Ltd. All rights reserved.
Full Text Available Influenza is a major respiratory pathogen causing annual outbreaks and occasional pandemics. Influenza vaccination is the major method of prophylaxis. Currently annual influenza vaccination is recommended for groups at high risk of complications from influenza infection such as pregnant women, young children, people with underlying disease and the elderly, along with occupational groups such a healthcare workers and farm workers. There are two main types of vaccines available: the parenteral inactivated influenza vaccine and the intranasal live attenuated influenza vaccine. The inactivated vaccines are licensed from 6 months of age and have been used for more than 50 years with a good safety profile. Inactivated vaccines are standardized according to the presence of the viral major surface glycoprotein hemagglutinin and protection is mediated by the induction of vaccine strain specific antibody responses. In contrast, the live attenuated vaccines are licensed in Europe for children from 2–17 years of age and provide a multifaceted immune response with local and systemic antibody and T cell responses but with no clear correlate of protection. Here we discuss the immunological immune responses elicited by the two vaccines and discuss future work to better define correlates of protection.
Troy, Stephanie B.; Kouiavskaia, Diana; Siik, Julia; Kochba, Efrat; Beydoun, Hind; Mirochnitchenko, Olga; Levin, Yotam; Khardori, Nancy; Chumakov, Konstantin; Maldonado, Yvonne
Background. Inactivated polio vaccine (IPV) is necessary for global polio eradication because oral polio vaccine can rarely cause poliomyelitis as it mutates and may fail to provide adequate immunity in immunocompromised populations. However, IPV is unaffordable for many developing countries. Intradermal IPV shows promise as a means to decrease the effective dose and cost of IPV, but prior studies, all using 20% of the standard dose used in intramuscular IPV, resulted in inferior antibody tit...
Zuccotti, Gian Vincenzo; Fabiano, Valentina
Influenza represents a major sanitary and socio-economic burden and vaccination is universally considered the most effective strategy for preventing the disease and its complications. Traditional influenza vaccines have been on the market since the late 1940s, with million of doses administered annually worldwide, and demonstrated a substantial efficacy and safety. The trivalent inactivated subunit vaccine has been available for more than 25 years and has been studied in healthy children, adults and the elderly and in people affected by underlying chronic medical conditions. We describe vaccine technology focusing on subunit vaccine production procedures and mode of action and provide updated information on efficacy and safety available data. A review of efficacy and safety data in healthy subjects and in high risk populations from major sponsor- and investigator-driven studies. The vaccine showed a good immunogenicity and a favorable safety profile in all target groups. In the panorama of actually available influenza vaccines, trivalent inactivated subunit vaccine represents a well-established tool for preventing flu and the associated complications.
Korotkova, Ekaterina A; Gmyl, Anatoly P; Yakovenko, Maria L; Ivanova, Olga E; Eremeeva, Tatyana P; Kozlovskaya, Liubov I; Shakaryan, Armen K; Lipskaya, Galina Y; Parshina, Irina L; Loginovskikh, Nataliya V; Morozova, Nadezhda S; Agol, Vadim I
Four cases of acute flaccid paralysis caused by slightly evolved (Sabin-like) vaccine polioviruses of serotype 2 were registered in July to August 2010 in an orphanage of Biysk (Altai Region, Russia). The Biysk cluster of vaccine-associated paralytic poliomyelitis (VAPP) had several uncommon, if not unique, features. (i) Until this outbreak, Sabin-like viruses (in distinction to more markedly evolved vaccine-derived polioviruses [VDPVs]) were reported to cause only sporadic cases of VAPP. Consequently, VAPP cases were not considered to require outbreak-type responses. However, the Biysk outbreak completely blurred the borderline between Sabin-like viruses and VDPVs in epidemiological terms. (ii) The outbreak demonstrated a very high disease/infection ratio, apparently exceeding even that reported for wild polioviruses. The viral genome structures did not provide any substantial hints as to the underlying reason(s) for such pathogenicity. (iii) The replacement of intestinal poliovirus lineages by other Sabin-like lineages during short intervals after the disease onsets was observed in two patients. Again, the sequences of the respective genomes provided no clues to explain these events. (iv) The polioviruses isolated from the patients and their contacts demonstrated a striking heterogeneity as well as rapid and uneven evolution of the whole genomes and their parts, apparently due to extensive interpersonal contacts in a relatively small closed community, multiple bottlenecking, and recombination. Altogether, the results demonstrate several new aspects of pathogenicity, epidemiology, and evolution of vaccine-related polioviruses and underscore several serious gaps in understanding these problems. The oral poliovirus vaccine largely contributed to the nearly complete disappearance of poliovirus-caused poliomyelitis. Being generally safe, it can, in some cases, result in a paralytic disease. Two types of such outcomes are distinguished: those caused by slightly
Immunogenicity, safety, and antibody persistence at 3, 5, and 10 years postvaccination in adolescents randomized to booster immunization with a combined tetanus, diphtheria, 5-component acellular pertussis, and inactivated poliomyelitis vaccine administered with a hepatitis B virus vaccine concurrently or 1 month apart.
Embree, Joanne; Law, Barbara; Voloshen, Tim; Tomovici, Antigona
An understanding of the antibody persistence elicited by a combined tetanus, diphtheria, 5-component acellular pertussis, and inactivated poliovirus vaccine (Tdap-IPV) after adolescent vaccination is important to optimize booster dosing intervals. Our objectives were to compare the safety and immunogenicity of Tdap-IPV coadministered with hepatitis B vaccine (HepB) and sequential administration and evaluate humoral immunity at 3, 5, and 10 years after Tdap-IPV vaccination in adolescents. This phase II randomized, controlled, and open-label study enrolled 280 11- to 14-year-old adolescents with up to 10 years postvaccination follow-up. Group 1 (n = 145) received Tdap-IPV, followed by a HepB dose 1 month later, and group 2 (n = 135) received both vaccines simultaneously. No consistent increases in solicited reactions or unsolicited adverse events occurred with coadministration. All vaccinees attained seroprotective antibody levels at ≥0.01 IU/ml for diphtheria and tetanus, at a ≥1:8 dilution for poliovirus (serotypes 1, 2, and 3), and ≥10 mIU/ml for hepatitis B at 1 month postvaccination. Clinically relevant immunologic interactions did not occur with coadministration. For pertussis, all participants achieved seropositivity levels (at or above the lower limit of quantitation), and 72.7% to 95.8% had 4-fold increases in pertussis antibodies at 1 month postvaccination. At 10 years postvaccination, the remaining participants (62.8% of the original cohort) maintained seroprotective levels of ≥0.01 IU/ml for diphtheria and tetanus, a ≥1:8 dilution for all 3 poliovirus serotypes, and 74.1% to 98.2% maintained pertussis seropositivity levels depending on the antigen tested. There were no differences between the groups. These results support the coadministration of Tdap-IPV and HepB to adolescents and suggest that vaccination with Tdap-IPV can offer protection for 10 years after an adolescent booster vaccination. Copyright © 2015, American Society for Microbiology
Browne, Cameron J; Smith, Robert J; Bourouiba, Lydia
Mass-vaccination campaigns are an important strategy in the global fight against poliomyelitis and measles. The large-scale logistics required for these mass immunisation campaigns magnifies the need for research into the effectiveness and optimal deployment of pulse vaccination. In order to better understand this control strategy, we propose a mathematical model accounting for the disease dynamics in connected regions, incorporating seasonality, environmental reservoirs and independent periodic pulse vaccination schedules in each region. The effective reproduction number, Re, is defined and proved to be a global threshold for persistence of the disease. Analytical and numerical calculations show the importance of synchronising the pulse vaccinations in connected regions and the timing of the pulses with respect to the pathogen circulation seasonality. Our results indicate that it may be crucial for mass-vaccination programs, such as national immunisation days, to be synchronised across different regions. In addition, simulations show that a migration imbalance can increase Re and alter how pulse vaccination should be optimally distributed among the patches, similar to results found with constant-rate vaccination. Furthermore, contrary to the case of constant-rate vaccination, the fraction of environmental transmission affects the value of Re when pulse vaccination is present.
During the endgame of global polio eradication, the universal introduction of inactivated poliovirus vaccines is urgently required to reduce the risk of vaccine-associated paralytic poliomyelitis and polio outbreaks due to wild and vaccine-derived polioviruses. In particular, the development of inactivated poliovirus vaccines (IPVs) derived from the attenuated Sabin strains is considered to be a highly favorable option for the production of novel IPV that reduce the risk of facility-acquired transmission of poliovirus to the communities. In Japan, Sabin-derived IPVs (sIPVs) have been developed and introduced for routine immunization in November 2012. They are the first licensed sIPVs in the world. Consequently, trivalent oral poliovirus vaccine was used for polio control in Japan for more than half a century but has now been removed from the list of vaccines licensed for routine immunization. This paper reviews the development, introduction, characterization, and global status of IPV derived from attenuated Sabin strains. Copyright © 2014 Elsevier Ltd. All rights reserved.
Rodríguez Sánchez, Juan Antonio
Full Text Available Two anti-poliomyelitic vaccination campaigns coexisted in 1963: the Salk vaccine used by the Compulsory Health Insurance and the pilot experience with the oral Sabin vaccine promoted by the Health General Office. This simultaneity of campaigns was due to the interest that both bodies had to control the Preventive Medicine in Spain. The Compulsory Sickness Insurance used the antipolio vaccine to promote itself socially in a time when the Basic Law on Social Security was being developed. Under these circumstances, the Health General Office allegedly brought forward its vaccine campaign by using a test of an innovative oral trivalent vaccine in the province of León, something which was hidden to the public. The Health General Office’s claim of competence in prevention and the need of a massive response to a voluntary vaccine led to a singular advertising campaign with old messages in innovative means of communication.
En 1963 coexistieron en el tiempo dos campañas de vacunación antipoliomielítica: la llevada a cabo con vacuna Salk por el Seguro Obligatorio de Enfermedad y la experiencia piloto con vacuna oral Sabin que promovió la Dirección General de Sanidad. La simultaneidad obedecía a la pugna entre ambos organismos por controlar la Medicina Preventiva en España. El Seguro Obligatorio de Enfermedad utilizó la vacunación antipolio para promocionarse socialmente en unos momentos de gestación de la Ley de Bases de la Seguridad Social. En estas circunstancias, la Dirección General de Sanidad debió anticipar su campaña de vacunación mediante un ensayo de una novedosa vacuna trivalente oral en la provincia de León, aspectos que fueron ocultados a la población. La reivindicación de su competencia en la prevención y la necesidad de una respuesta masiva ante una vacunación voluntaria originaron una singular campaña publicitaria de añejos mensajes pero en novedosos medios de comunicación.
Salmon, J H; Geoffroy, M; Eschard, J P; Ohl, X
Revaxis(®) is a vaccine against diphtheria, tetanus and poliomyelitis (dT-IPV). This vaccine should not be administered by the intradermal or intravenous route. Poor injection techniques and related consequences are rare. We report a case of bursitis associated with reactive glenohumeral effusion complicated by bone erosion occurring after injection of the dT-IPV vaccine. A 26 year old patient was admitted for painful left shoulder causing functional impairment. Control magnetic resonance imaging showed bone oedema on the upper outer part of the humeral head, with a slight cortical irregularity, indicating that the vaccine was injected in contact with the bone at this location, causing erosion. Outcome was favourable after intra-articular corticosteroids. Reports of articular or periarticular injury after vaccination are extremely rare, in view of the substantial number of vaccines administered every year. The potential complications of vaccination are well known to general practitioners but under-reported in the literature. Copyright © 2015 Elsevier Ltd. All rights reserved.
Ivanova, O E; Eremeeva, T P; Morozova, N S; Shakaryan, A K; Gmyl, A P; Yakovenko, M L; Korotkova, E A; Chernjavskaja, O P; Baykova, O Yu; Silenova, O V; Krasota, A Yu; Krasnoproshina, L I; Mustafina, A N; Kozlovskaja, L I
The results of virologic testing of clinical materials and epidemiological analysis of vaccine-associated paralytic poliomyelitis (VAPP) cases obtained in 2006-2013 during AFP surveillance are presented. Among the 2976 cases of AFP 30 cases were VAPP. 15 cases were observed in OPV recipients, whereas 15 cases were observed in non-vaccinated contacts. The age of the patients varied from 4 months to 5.5 years (13.6 ± 12.4 months old). Children younger than 1 year constituted 63.3% of the group; boys were dominant (73.3%); 53.3% of children were vaccinated with OPV; the time period between receipt of OPV and onset of palsy was from 2 to 32 days (18.7 ± 8.2). Lower paraparesis was documented in 48.3% of patients; lower monoparesis in 37.9%; upper monoparesis, in 6.9%; tetraparesis with bulbar syndrome, in 6%. The majority of the patients (85.7%) had an unfavorable premorbid status. The violations of the humoral immunity were found in 73.9% cases: CVID (52.9%), hypogammaglobulinemia (41.2%); selective lgA deflciency (5.9%). In 70.6% cases damage to humoral immunity was combined with poor premorbid status. The most frequently observed (76%, p poliomyelitis in the Russian Federation, WHO Polio eradication initiative, WHO's European Regional Bureau, Russian Foundation for Basic Research (project No. 15-15-00147).
Lee, Hwee Ching; Tay, Joanne; Kwok, Cynthia Y H; Wee, Moi Kim; Ang, Li Wei; Kita, Yuske; Cutter, Jeffery L; Chan, Kwai Peng; Chew, Suok Kai; Goh, Kee Tai
This study reviewed the epidemiological trends of poliomyelitis from 1946 to 2010, and the impact of the national immunisation programme in raising the population herd immunity against poliovirus. We also traced the efforts Singapore has made to achieve certification of poliomyelitis eradication by the World Health Organisation. Epidemiological data on all reported cases of poliomyelitis were obtained from the Communicable Diseases Division of the Ministry of Health as well as historical records. Coverage of the childhood immunisation programme against poliomyelitis was based on the immunisation data maintained by the National Immunisation Registry, Health Promotion Board. To assess the herd immunity of the population against poliovirus, 6 serological surveys were conducted in 1962, 1978, 1982 to 1984, 1989, 1993 and from 2008 to 2010. Singapore was among the fi rst countries in the world to introduce live oral poliovirus vaccine (OPV) on a mass scale in 1958. With the comprehensive coverage of the national childhood immunisation programme, the incidence of paralytic poliomyelitis declined from 74 cases in 1963 to 5 cases from 1971 to 1973. The immunisation coverage for infants, preschool and primary school children has been maintained at 92% to 97% over the past decade. No indigenous poliomyelitis case had been reported since 1978 and all cases reported subsequently were imported. Singapore was certified poliomyelitis free along with the rest of the Western Pacific Region in 2000 after fulfilling all criteria for poliomyelitis eradication, including the establishment of a robust acute flaccid paralysis surveillance system. However, post-certification challenges remain, with the risk of wild poliovirus importation. Furthermore, it is timely to consider the replacement of OPV with the inactivated poliovirus vaccine in Singapore's national immunisation programme given the risk of vaccine-associated paralytic poliomyelitis and circulating vaccine-derived polioviruses.
Lopes Ferraz-Filho, Jose Roberto; Santos Torres, Ulysses dos; Portela de Oliveira, Eduardo; Soares Souza, Antonio
Although acute flaccid paralysis is a manifestation observed in several neurologic and muscular disorders, vaccine-associated paralytic poliomyelitis (VAPP) is an exceedingly rare etiology. In the clinical setting of acute flaccid paralysis, MRI is useful in differentiating between VAPP and other conditions. Additionally, MRI can assess the extent of lesions. However, reports on MRI findings in VAPP are scarce in the pediatric radiology literature. We report a Brazilian infant who developed VAPP 40 days after receiving the first dose of oral polio vaccine (OPV). MR images of the cervical and thoracic spinal cord showed lesions involving the anterior horn cell, with increased signal intensity on T2-weighted sequences. We would like to emphasize the importance of considering VAPP as a differential diagnosis in patients with acute flaccid paralysis and an MRI showing involvement of medulla oblongata or spinal cord, particularly in countries where OPV is extensively administered. (orig.)
Lopes Ferraz-Filho, Jose Roberto [Sao Jose do Rio Preto Medical School, Department of Radiology, Hospital de Base, Sao Paulo, State (Brazil); Sao Jose do Rio Preto Medical School, Department of Radiology, Sao Jose do Rio Preto, Sao Paulo State (Brazil); Santos Torres, Ulysses dos; Portela de Oliveira, Eduardo; Soares Souza, Antonio [Sao Jose do Rio Preto Medical School, Department of Radiology, Hospital de Base, Sao Paulo, State (Brazil)
Although acute flaccid paralysis is a manifestation observed in several neurologic and muscular disorders, vaccine-associated paralytic poliomyelitis (VAPP) is an exceedingly rare etiology. In the clinical setting of acute flaccid paralysis, MRI is useful in differentiating between VAPP and other conditions. Additionally, MRI can assess the extent of lesions. However, reports on MRI findings in VAPP are scarce in the pediatric radiology literature. We report a Brazilian infant who developed VAPP 40 days after receiving the first dose of oral polio vaccine (OPV). MR images of the cervical and thoracic spinal cord showed lesions involving the anterior horn cell, with increased signal intensity on T2-weighted sequences. We would like to emphasize the importance of considering VAPP as a differential diagnosis in patients with acute flaccid paralysis and an MRI showing involvement of medulla oblongata or spinal cord, particularly in countries where OPV is extensively administered. (orig.)
Aaby, Peter; Ravn, Henrik; Benn, Christine S.
Background: Observational studies have suggested that girls have higher mortality if their most recent immunization is an inactivated vaccine rather than a live vaccine. We therefore reanalyzed 5 randomized trials of early measles vaccine (MV) in which it was possible to compare an inactivated va...
Sun, Mingbo; Li, Changgui; Xu, Wenbo; Liao, Guoyang; Li, Rongcheng; Zhou, Jian; Li, Yanping; Cai, Wei; Yan, Dongmei; Che, Yanchun; Ying, Zhifang; Wang, Jianfeng; Yang, Huijuan; Ma, Yan; Ma, Lei; Ji, Guang; Shi, Li; Jiang, Shude; Li, Qihan
A Sabin strain-based inactivated poliomyelitis vaccine (Sabin-IPV) is the rational option for completely eradicating poliovirus transmission. The neutralizing capacity of Sabin-IPV immune serum to different strains of poliovirus is a key indicator of the clinical protective efficacy of this vaccine. Sera collected from 500 infants enrolled in a randomized, blinded, positive control, phase 2 clinical trial were randomly divided into 5 groups: Groups A, B, and C received high, medium, and low doses, respectively, of Sabin-IPV, while groups D and E received trivalent oral polio vaccine and Salk strain-based IPV, respectively, all on the same schedule. Immune sera were collected after the third dose of primary immunization, and tested in cross-neutralization assays against 19 poliovirus strains of all 3 types. All immune sera from all 5 groups interacted with the 19 poliovirus strains with various titers and in a dose-dependent manner. One type 2 immunodeficiency-associated vaccine-derived poliovirus strain was not recognized by these immune sera. Sabin-IPV vaccine can induce protective antibodies against currently circulating and reference wild poliovirus strains and most vaccine-derived poliovirus strains, with rare exceptions. NCT01056705. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: firstname.lastname@example.org.
O'Reilly, K M; Cori, A; Durry, E; Wadood, M Z; Bosan, A; Aylward, R B; Grassly, N C
Mass vaccination campaigns with the oral poliovirus vaccine targeting children aged poliomyelitis eradication effort. Monitoring the coverage of these campaigns is essential to allow corrective action, but current approaches are limited by their cross-sectional nature, nonrandom sampling, reporting biases, and accessibility issues. We describe a new Bayesian framework using data augmentation and Markov chain Monte Carlo methods to estimate variation in vaccination coverage from children's vaccination histories investigated during surveillance for acute flaccid paralysis. We tested the method using simulated data with at least 200 cases and were able to detect undervaccinated groups if they exceeded 10% of all children and temporal changes in coverage of ±10% with greater than 90% sensitivity. Application of the method to data from Pakistan for 2010-2011 identified undervaccinated groups within the Balochistan/Federally Administered Tribal Areas and Khyber Pakhtunkhwa regions, as well as temporal changes in coverage. The sizes of these groups are consistent with the multiple challenges faced by the program in these regions as a result of conflict and insecurity. Application of this new method to routinely collected data can be a useful tool for identifying poorly performing areas and assisting in eradication efforts. © The Author 2015. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.
Kraan, H.; Have, Ten R.; Maas, van der L.; Kersten, G.F.A.; Amorij, J.P.
A hexavalent vaccine containing diphtheria toxoid, tetanus toxoid, whole cell pertussis, Haemophilius influenza type B, hepatitis B and inactivated polio vaccine (IPV) may: (i) increase the efficiency of vaccination campaigns, (ii) reduce the number of injections thereby reducing needlestick
Thomassen, Y.E.; Oever, van 't R.; Vinke, C.M.; Spiekstra, A.; Wijffels, R.H.; Pol, van der L.A.; Bakker, W.A.M.
The anticipated increase in the demand for inactivated polio vaccines resulting from the success in the polio eradication program requires an increase in production capacity and cost price reduction of the current inactivated polio vaccine production processes. Improvement of existing production
Shirreff, George; Wadood, Mufti Zubair; Vaz, Rui Gama; Sutter, Roland W; Grassly, Nicholas C
In 2014, inactivated poliovirus vaccine (IPV) campaigns were implemented in Nigeria and Pakistan after clinical trials showed that IPV boosts intestinal immunity in children previously given oral poliovirus vaccine (OPV). We estimated the effect of these campaigns by using surveillance data collected during January 2014-April 2016. In Nigeria, campaigns with IPV and trivalent OPV (tOPV) substantially reduced the incidence of poliomyelitis caused by circulating serotype-2 vaccine-derived poliovirus (incidence rate ratio [IRR] 0.17 for 90 days after vs. 90 days before campaigns, 95% CI 0.04-0.78) and the prevalence of virus in environmental samples (prevalence ratio [PR] 0.16, 95% CI 0.02-1.33). Campaigns with tOPV alone resulted in similar reductions (IRR 0.59, 95% CI 0.18-1.97; PR 0.45, 95% CI 0.21-0.95). In Pakistan, the effect of IPV+tOPV campaigns on wild-type poliovirus was not significant. Results suggest that administration of IPV alongside OPV can decrease poliovirus transmission if high vaccine coverage is achieved.
Full Text Available An interference is observed between whooping-cough antigens and Salk polioc vaccine even if the two components are mixed immediately before use. The phenomenon is more evident when flUlid antigens are injected. Pertussis soluble antigen, which gives a good serological response in rabbits, when used alone or combined with DT, is inactivated in the presence of Salk polio vacc:ne
van der Maas, N A; Mollema, L; Berbers, G A; van Rooijen, D M; van der Avoort, H G; Conyn-Van Spaendonck, M A; de Melker, H E; van der Klis, F R
Europe has been declared polio-free since 2002. Here we describe the seroprotection against poliomyelitis in the Dutch population using banked serum samples. Samples from 1,581 inhabitants of eight municipalities with low vaccination coverage (LVC) and an additional 6,386 samples from a nationwide (NS) group (clinical trial number: ISRCTN20164309; collected in 2006–07) were tested for neutralising antibodies (log² reciprocal titres (GMT); non-protection poliomyelitis serotypes. Demographic and epidemiological data were used for statistical regression analysis. Seroprevalence in the NS was 94.6% (type 1), 91.8% (type 2) and 84.0% (type 3). Infants (0–7 months-old) had ≥80% seroprevalence for all serotypes. The highest seroprevalence was found in children, with type 1 and type 2 in five year-olds and type 3 in nine to 10 year-olds. In the LVC group, orthodox protestants, many of whom refuse vaccination, showed seroprevalence rates of 64.9% (type 1), 61.0% (type 2) and 62.1% (type 3). In the NS group, non-Western immigrants and travellers to non-European continents had higher seroprevalences compared to Western immigrants and travellers within Europe, respectively. The Dutch National Immunisation Programme against poliomyelitis has provided good seroprotection, with high and long-lasting GMTs against all serotypes upon completion. The unvaccinated population remains at risk.
Wilson, J H; Hermann-Dekkers, W M; Leemans-Dessy, S; Meijer, J W
A fluid adjuvanted vaccine consisting of inactivated hepatitis virus (iH) and leptospirae antigens (L) was developed. The vaccine (Kavak iHL; Duphar) was tested in several vaccination programmes both alone and in combination with freeze dried measles (M) or distemper (D) vaccines. The results demonstrate that this new vaccine is also effective in pups with maternally derived antibodies, although a second vaccination at 14 weeks of age is recommended to boost the first vaccination. For the booster vaccination either the iHL-vaccine or the liver attenuated hepatitis vaccine (H) can be used.
O'Reilly, Kathleen M; Durry, Elias; ul Islam, Obaid; Quddus, Arshad; Abid, Ni'ma; Mir, Tahir P; Tangermann, Rudi H; Aylward, R Bruce; Grassly, Nicholas C
Pakistan and Afghanistan are two of the three remaining countries yet to interrupt wild-type poliovirus transmission. The increasing incidence of poliomyelitis in these countries during 2010-11 led the Executive Board of WHO in January, 2012, to declare polio eradication a "programmatic emergency for global public health". We aimed to establish why incidence is rising in these countries despite programme innovations including the introduction of new vaccines. We did a matched case-control analysis based on a database of 46,977 children aged 0-14 years with onset of acute flaccid paralysis between Jan 1, 2001, and Dec 31, 2011. The vaccination history of children with poliomyelitis was compared with that of children with acute flaccid paralysis due to other causes to estimate the clinical effectiveness of oral poliovirus vaccines (OPVs) in Afghanistan and Pakistan by conditional logistic regression. We estimated vaccine coverage and serotype-specific vaccine-induced population immunity in children aged 0-2 years and assessed their association with the incidence of poliomyelitis over time in seven regions of Afghanistan and Pakistan. Between Jan 1, 2001, and Dec 31, 2011, there were 883 cases of serotype 1 poliomyelitis (710 in Pakistan and 173 in Afghanistan) and 272 cases of poliomyelitis serotype 3 (216 in Pakistan and 56 in Afghanistan). The estimated clinical effectiveness of a dose of trivalent OPV against serotype 1 poliomyelitis was 12·5% (95% CI 5·6-18·8) compared with 34·5% (16·1-48·9) for monovalent OPV (p=0·007) and 23·4% (10·4-34·6) for bivalent OPV (p=0·067). Bivalent OPV was non-inferior compared with monovalent OPV (p=0·21). Vaccination coverage decreased during 2006-11 in the Federally Administered Tribal Areas (FATA), Balochistan, and Khyber Pakhtunkhwa in Pakistan and in southern Afghanistan. Although partially mitigated by the use of more effective vaccines, these decreases in coverage resulted in lower vaccine-induced population
O'Reilly, Kathleen M; Durry, Elias; ul Islam, Obaid; Quddus, Arshad; Abid, Ni'ma; Mir, Tahir P; Tangermann, Rudi H; Aylward, R Bruce; Grassly, Nicholas C
Summary Background Pakistan and Afghanistan are two of the three remaining countries yet to interrupt wild-type poliovirus transmission. The increasing incidence of poliomyelitis in these countries during 2010–11 led the Executive Board of WHO in January, 2012, to declare polio eradication a “programmatic emergency for global public health”. We aimed to establish why incidence is rising in these countries despite programme innovations including the introduction of new vaccines. Methods We did a matched case-control analysis based on a database of 46 977 children aged 0–14 years with onset of acute flaccid paralysis between Jan 1, 2001, and Dec 31, 2011. The vaccination history of children with poliomyelitis was compared with that of children with acute flaccid paralysis due to other causes to estimate the clinical effectiveness of oral poliovirus vaccines (OPVs) in Afghanistan and Pakistan by conditional logistic regression. We estimated vaccine coverage and serotype-specific vaccine-induced population immunity in children aged 0–2 years and assessed their association with the incidence of poliomyelitis over time in seven regions of Afghanistan and Pakistan. Findings Between Jan 1, 2001, and Dec 31, 2011, there were 883 cases of serotype 1 poliomyelitis (710 in Pakistan and 173 in Afghanistan) and 272 cases of poliomyelitis serotype 3 (216 in Pakistan and 56 in Afghanistan). The estimated clinical effectiveness of a dose of trivalent OPV against serotype 1 poliomyelitis was 12·5% (95% CI 5·6–18·8) compared with 34·5% (16·1–48·9) for monovalent OPV (p=0·007) and 23·4% (10·4–34·6) for bivalent OPV (p=0·067). Bivalent OPV was non-inferior compared with monovalent OPV (p=0·21). Vaccination coverage decreased during 2006–11 in the Federally Administered Tribal Areas (FATA), Balochistan, and Khyber Pakhtunkhwa in Pakistan and in southern Afghanistan. Although partially mitigated by the use of more effective vaccines, these decreases in
Full Text Available Infectious bronchitis (IB is an acute highly contagious viral respiratory disease of poultry caused by coronavirus. The disease causes high mortality in young chicks, reduce body weight gain in broilers and remarkable drop in egg production. IB can only be controlled by vaccination, but due to the antigenic variation among serotypes of IB viruses, the effective IB vaccine should be prepared from local isolates. The aim of this research is to develop inactivated IB vaccine derived from local IB isolates. Local isolates of IB viruses designated as I-37, I-269 and PTS-III were propagated respectively in specific pathogen free (SPF chicken eggs, the viruses then were inactivated by formaline at final concentration of 1:1,000. Subsequently, the inactivated viruses were mixed and emulsified in oil emulsion adjuvant with sorbitant mono-oleic as an emulsifier. The vaccine then was tested for its safety, potency and efficacy in broiler chickens. Birds inoculated twice with a two-week interval by inactivated vaccine did not show any adverse reaction, either systemic or local reaction. The inoculated birds developed antibody responses with high titre, while antibody of the control birds remain negative. In addition, efficacy test which was conducted in broilers demonstrated that birds vaccinated by live-commercial vaccine and boosted three weeks later by Balitvet inactivated vaccine showed high level of antibody production which provided high level of protection against challenged virus (76% against I-37, 92% against I-269 and 68% against PTS-III challenge viruses. From this study, it can be concluded that inactivated local IB vaccine is considered to be safe, potent and efficacious. The vaccine stimulates high titre of antibody responses, which provide high level of protection against challenged viruses.
Full Text Available The article presents the results of the observation of 200 children under the age 18–42 months (64 healthy children and 136 patients with allergic symptoms, residual lesions of CNS, frequently ailing children, and having reactions of previous vaccination in medical history who were re-vaccinated with vaccine Pentaxim. It was shown that 77% of children had asymptomatic post-vaccinal period. Only 1,5% of patients showed severe reactions with fever > 38,6_С. Local reactions (not over 3–5 cm developed in 25,5% of children with allergy, lesions of CNS and frequently ailing children, their rate was significantly higher than in healthy children (7,8%. No one had post-vaccinal complications. An estimation of reactogenicity of vaccine proved its safety and suitability of administration as first re-vaccination against pertussis, diphtheria, tetanus, poliomyelitis and one-time vaccination against Haemophilus influenzae type b in children after 1 year old in different state of health.Key words: children, vaccinations, Pentaxim, post-vaccinal period, safety.(Voprosy sovremennoi pediatrii — Current Pediatrics. 2009;8(6:20-25
Full Text Available Poliomyelitis has nearly been eradicated through the efforts of the World Health Organization's Global Eradication Initiative raising questions on containment of the virus after it has been eliminated in the wild. Most manufacture of inactivated polio vaccines currently requires the growth of large amounts of highly virulent poliovirus, and release from a production facility after eradication could be disastrous; WHO have therefore recommended the use of the attenuated Sabin strains for production as a safer option although it is recognised that they can revert to a transmissible paralytic form. We have exploited the understanding of the molecular virology of the Sabin vaccine strains to design viruses that are extremely genetically stable and hyperattenuated. The viruses are based on the type 3 Sabin vaccine strain and have been genetically modified in domain V of the 5' non-coding region by changing base pairs to produce a cassette into which capsid regions of other serotypes have been introduced. The viruses give satisfactory yields of antigenically and immunogenically correct viruses in culture, are without measurable neurovirulence and fail to infect non-human primates under conditions where the Sabin strains will do so.
Knowlson, Sarah; Burlison, John; Giles, Elaine; Fox, Helen; Macadam, Andrew J; Minor, Philip D
Poliomyelitis has nearly been eradicated through the efforts of the World Health Organization's Global Eradication Initiative raising questions on containment of the virus after it has been eliminated in the wild. Most manufacture of inactivated polio vaccines currently requires the growth of large amounts of highly virulent poliovirus, and release from a production facility after eradication could be disastrous; WHO have therefore recommended the use of the attenuated Sabin strains for production as a safer option although it is recognised that they can revert to a transmissible paralytic form. We have exploited the understanding of the molecular virology of the Sabin vaccine strains to design viruses that are extremely genetically stable and hyperattenuated. The viruses are based on the type 3 Sabin vaccine strain and have been genetically modified in domain V of the 5' non-coding region by changing base pairs to produce a cassette into which capsid regions of other serotypes have been introduced. The viruses give satisfactory yields of antigenically and immunogenically correct viruses in culture, are without measurable neurovirulence and fail to infect non-human primates under conditions where the Sabin strains will do so.
Shirreff, George; Wadood, Mufti Zubair; Vaz, Rui Gama; Sutter, Roland W.
In 2014, inactivated poliovirus vaccine (IPV) campaigns were implemented in Nigeria and Pakistan after clinical trials showed that IPV boosts intestinal immunity in children previously given oral poliovirus vaccine (OPV). We estimated the effect of these campaigns by using surveillance data collected during January 2014–April 2016. In Nigeria, campaigns with IPV and trivalent OPV (tOPV) substantially reduced the incidence of poliomyelitis caused by circulating serotype-2 vaccine–derived poliovirus (incidence rate ratio [IRR] 0.17 for 90 days after vs. 90 days before campaigns, 95% CI 0.04–0.78) and the prevalence of virus in environmental samples (prevalence ratio [PR] 0.16, 95% CI 0.02–1.33). Campaigns with tOPV alone resulted in similar reductions (IRR 0.59, 95% CI 0.18–1.97; PR 0.45, 95% CI 0.21–0.95). In Pakistan, the effect of IPV+tOPV campaigns on wild-type poliovirus was not significant. Results suggest that administration of IPV alongside OPV can decrease poliovirus transmission if high vaccine coverage is achieved. PMID:27861118
Ljubin-Sternak, Sunčanica; Kaić, Bernard; Vilibić-Čavlek, Tatjana; Mlinarić-Galinović, Gordana
Poliomyelitis is a very old disease of humans, caused by poliovirus. With appearance of the epidemics in the 20th century, poliomyelitis became a global public health issue. In 1988, the World Health Organization started a campaign for global eradication of poliomyelitis and till now poliomyelitis cases have been reduced by more than 99%. In Croatia, the introduction of vaccination in 1961 resulted in dramatic reduction of paralytic disease. The European region, including Croatia was certified polio free in 2002. However, the final goal of the "polio-free world" has not yet been reached. To reinforce the campaign, the global polio eradication initiative has come up with the Polio Eradication & Endgame Strategic Plan 2013-2018 with detailed program how to resolve the main challenges: (a) continued transmission of wild polioviruses in endemic reservoirs; (b) reinfection of polio-free areas; and (c) outbreaks due to the circulating vaccine-derived polioviruses (cVDPV). Global oral polio vaccine cessation will follow, with the introduction of universal use of inactivated polio vaccine.
Heinsbroek, E.; Ruitenberg, E.J.
This literature review identifies the factors that influence the decision to introduce inactivated polio vaccine (IPV) in developing countries as opposed to the policy of vaccine cessation. Attenuated viruses in the oral polio vaccine (OPV) can replicate, revert to neurovirulence and become
... taken in its entirety from the CDC Inactivated Influenza Vaccine Information Statement (VIS) www.cdc.gov/vaccines/hcp/vis/vis-statements/flu.html CDC review information for Inactivated Influenza VIS: ...
Kouiavskaia, Diana; Mirochnitchenko, Olga; Dragunsky, Eugenia; Kochba, Efrat; Levin, Yotam; Troy, Stephanie; Chumakov, Konstantin
Intradermal delivery of vaccines has been shown to result in dose sparing. We tested the ability of fractional doses of inactivated poliovirus vaccine (IPV) delivered intradermally to induce levels of serum poliovirus-neutralizing antibodies similar to immunization through the intramuscular route. Immunogenicity of fractional doses of IPV was studied by comparing intramuscular and intradermal immunization of Wistar rats using NanoPass MicronJet600 microneedles. Intradermal delivery of partial...
Foiadelli, Thomas; Savasta, Salvatore; Battistone, Andrea; Kota, Majlinda; Passera, Carolina; Fiore, Stefano; Bino, Silvia; Amato, Concetta; Lozza, Alessandro; Marseglia, Gian Luigi; Fiore, Lucia
Vaccine-associated paralytic poliomyelitis (VAPP) and immunodeficient long-term polio excretors constitute a significant public health burden and are a major concern for the WHO global polio eradication endgame. Poliovirus type 3 characterized as Sabin-like was isolated from a 5-month-old Albanian child with X-linked agammaglobulinemia and VAPP after oral polio vaccine administration. Diagnostic workup and treatment were performed in Italy. Poliovirus replicated in the gut for 7 months. The 5' non coding region (NCR), VP1, VP3 capsid proteins and the 3D polymerase genomic regions of sequential isolates were sequenced. Increasing accumulation of nucleotide mutations in the VP1 region was detected over time, reaching 1.0 % of genome variation with respect to the Sabin reference strain, which is the threshold that defines a vaccine-derived poliovirus (VDPV). We identified mutations in the 5'NCR and VP3 regions that are associated with reversion to neurovirulence. Despite this, all isolates were characterized as Sabin-like. Several amino acid mutations were identified in the VP1 region, probably involved in growth adaptation and viral persistence in the human gut. Intertypic recombination with Sabin type 2 polio in the 3D polymerase region, possibly associated with increased virus transmissibility, was found in all isolates. Gamma-globulin replacement therapy led to viral clearance and neurological improvement, preventing the occurrence of persistent immunodeficiency-related VDPV. This is the first case of VAPP in an immunodeficient child detected in Albania through the Acute Flaccid Paralysis surveillance system and the first investigated case of vaccine associated poliomyelitis in Italy since the introduction of an all-Salk schedule in 2002. We discuss over the biological and clinical implications in the context of the Global Polio Eradication Program and emphasize on the importance of the Acute Flaccid Paralysis surveillance.
Li, Zhuofan; Ding, Wenting; Guo, Qi; Liu, Ze; Zhu, Zhe; Song, Shaohui; Li, Weidong; Liao, Guoyang
Sabin-based inactivated poliovirus vaccine(sIPV) is gradually replacing live-attenuated oral polio vaccine(OPV). Sabin-inactivated poliovirus vaccine(sIPV) has played a vital role in reducing economic burden of poliomyelitis and maintaining appropriate antibody levels in the population. However, due to its high cost and limited manufacturing capacity, sIPV cannot reach its full potential for global poliovirus eradication in developing countries. Therefore, to address this situation, we designed this study to evaluate the dose-sparing effects of AS03, CpG oligodeoxynucleotides (CpG-ODN) and polyinosinic:polycytidylic acid (PolyI:C) admixed with sIPV in rats. Our results showed that a combination of 1/4-dose sIPV adjuvanted with AS03 or AS03 with BW006 provides a seroconversion rate similar to that of full-dose sIPV without adjuvant and that, this rate is 5-fold higher than that of 1/4-dose sIPV without adjuvant after the first immunization. The combination of AS03 or AS03 with BW006 as an adjuvant effectively reduced sIPV dose by at least 4-fold and induced both humoral and cellular immune responses. Therefore, our study revealed that the combination of AS03 or AS03 with BW006 is a promising adjuvant for sIPV development.
José A. Paz
Full Text Available Poliomyelitis associated with live strain vaccine is defined as the paralytic form of the acute anterior poliomyelitis related to the vaccine strain. Since these strains behave similarly to the wild-type virus, we can differentiate, epidemiologically, two types of vaccine-associated poliomyelitis: cases in which the patient was vaccinated and cases in which the patient had had contact with vaccinated individuals. We herein present the case of an unvaccinated child, with a clinical picture of an acute anterior poliomyelitis associated with the live strain vaccine, whose brother received the Sabin vaccine 20 days before the onset of the symptoms. Vaccine strain of the type 3 poliovirus was isolated in fecal culture and a presented mutation in nucleotide 472 (C®U in the 5' non-coding region, which is strongly related to the higher strain virulence.A poliomielite associada à vacina oral é definida como a forma paralítica da poliomielite anterior aguda decorrente da cepa vacinal. Uma vez que o comportamento da cepa vacinal é semelhante ao do vírus selvagem, epidemiologicamente podemos distinguir dois tipos de poliomielite associada à vacina, os casos em que o paciente foi vacinado e os casos em que o paciente teve contato com pessoas que receberam a vacina. Apresentamos o caso de um lactente não vacinado, que apresentou quadro de poliomielite anterior aguda associada à vacina oral, cujo irmão havia recebido a vacina Sabin 20 dias antes do início do quadro clínico. Na cultura de fezes do paciente foi isolado o poliovírus tipo 3, cepa vacinal, que apresentava mutação do nucleotídeo 472 (C®U na região 5' não codificadora, a qual está significativamente relacionada com a maior virulência da cepa.
Full Text Available Abstract Background The most common cause of idiopathic nephrotic syndrome in children and younger adults is the minimal change nephrotic syndrome (MCNS. In the elderly MCNS is relatively uncommon. Over the last decade some reports suggest a rare but possible association with the administration of various vaccines. Case presentation A 82-year old Caucasian female presented with pronounced nephrotic syndrome (proteinuria of 7.1 g/d, hypoproteinemia of 47 g/l. About six weeks prior to admission, she had received a combination vaccination for tetanus, diphtheria and poliomyelitis as a booster-vaccination from her general practitioner. The renal biopsy revealed typical minimal change lesions. She responded well to the initiated steroid treatment. As through physical examination as well as extensive laboratory and imaging studies did neither find any evidence for malignancies nor infections we suggest that the minimal change nephrotic syndrome in this patient might be related to the activation of the immune system triggered by the vaccination. Conclusion Our case as well as previous anecdotal reports suggests that vaccination and the resulting stimulations of the immune system might cause MCNS and other severe immune-reactions. Increased awareness in that regard might help to expand the database of those cases.
Full Text Available The article considers the results of infantile mass vaccination with inactivated subunit influenza vaccine (Influvac. It shows that vaccination of 57–72% of children aged 3–17 from organized collectives residing in Mytishchi and Orekhovoczuevo districts of Moscow region was accompanied with nearly triple reduce of flu rates vs. Narofominsk and Odintsovo districts where vaccination was occasional (< 1% of children. The efficiency of the vaccination made 63,7%. Low reactogenicity of the influenza vaccine was recorded. Its convenient packing allows vaccination of large number of children in a short time. The article justifies the necessity of yearly vaccinations even in case of similarity of flu virus strain.Key words: children, mass vaccination, subunit flu vaccine, safety.
Patel, Manish; Zipursky, Simona; Orenstein, Walt; Garon, Julie; Zaffran, Michel
In 2013, the World Health Assembly endorsed a plan that calls for the ultimate withdrawal of oral polio vaccines (OPV) from all immunization programs globally. The withdrawal would begin in a phased manner with removal of the type 2 component of OPV in 2016 through a global switch from trivalent OPV to bivalent OPV (containing only types 1 and 3). To mitigate risks associated with immunity gaps after OPV type 2 withdrawal, the WHO Strategic Advisory Group of Experts has recommended that all 126 OPV-only using countries introduce at least one dose of inactivated polio vaccine into routine immunization programs by end-2015, before the trivalent OPV-bivalent OPV switch. The introduction of inactivated polio vaccine would reduce risks of reintroduction of type 2 poliovirus by providing some level of seroprotection, facilitating interruption of transmission if outbreaks occur, and accelerating eradication by boosting immunity to types 1 and 3 polioviruses.
Kouiavskaia, Diana; Mirochnitchenko, Olga; Dragunsky, Eugenia; Kochba, Efrat; Levin, Yotam; Troy, Stephanie; Chumakov, Konstantin
Intradermal delivery of vaccines has been shown to result in dose sparing. We tested the ability of fractional doses of inactivated poliovirus vaccine (IPV) delivered intradermally to induce levels of serum poliovirus-neutralizing antibodies similar to immunization through the intramuscular route. Immunogenicity of fractional doses of IPV was studied by comparing intramuscular and intradermal immunization of Wistar rats using NanoPass MicronJet600 microneedles. Intradermal delivery of partial vaccine doses induced antibodies at titers comparable to those after immunization with full human dose delivered intramuscularly. The results suggest that intradermal delivery of IPV may lead to dose-sparing effect and reduction of the vaccination cost. Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.
Mullaert, Jimmy; Abgrall, Sophie; Lele, Nathalie; Batteux, Frederic; Slama, Lilia Ben; Meritet, Jean-Francois; Lebon, Pierre; Bouchaud, Olivier; Grabar, Sophie; Launay, Odile
Few data are available on the seroprotection status of HIV1-infected patients with respect to vaccine-preventable diseases. To describe, in a population of HIV1-infected migrants on stable, effective ART therapy, the seroprevalence of diphtheria, poliomyelitis, tetanus, yellow fever antibodies and serostatus for hepatitis B, and to identify factors associated with seroprotection. Vaccine responses against diphtheria, tetanus, poliomyelitis and yellow fever were also studied. Sub-Saharan African patients participating in the ANRS-VIHVO cohort were enrolled prior to travel to their countries of origin. Serologic analyses were performed in a central laboratory before and after the trip. Univariate and multivariate logistic regression was used to identify factors associated with initial seroprotection. 250 patients (99 men and 151 women) were included in the seroprevalence study. Median age was 45 years (IQR 39-52), median CD4 cell count was 440/μL (IQR 336-571), and 237 patients (95%) had undetectable HIV1 viral load. The initial seroprevalence rates were 69.0% (95%CI 63.2-74.7) for diphtheria, 70.7% (95%CI 65.0-76.3) for tetanus, and 85.9% (95%CI 81.6-90.2) for yellow fever. Only 64.4% (95%CI 58.5-70.3) of patients had protective antibody titers against all three poliomyelitis vaccine strains before travel. No serological markers of hepatitis B were found in 18.6% of patients (95%CI 13.7-23.3). Patient declaration of prior vaccination was the only factor consistently associated with initial seroprotection. We found a low prevalence of seroprotection against diphtheria, poliomyelitis, tetanus and hepatitis B. HIV infected migrants living in France and traveling to their native countries need to have their vaccine schedule completed. Copyright © 2015 Elsevier Ltd. All rights reserved.
T. R. Gopalakrishnamurthy
Full Text Available Aim: To evaluate an inactivated vaccine for nephropathogenic infectious bronchitis in broiler with special reference to its ability for passing maternal antibodies to broiler chicks. Materials and Methods: An inactivated vaccine against nephropathogenic infectious bronchitis (NIB, prepared using an isolate obtained from natural outbreak of NIB was administered to broiler parents at the point of lay, leaving the control birds unvaccinated. Eggs laid below the desired weight (> 52 g by vaccinated hens were utilized for yolk serology. Chicks obtained from hens of both group were subjected for serology and challenge with wild type of nephropathogenic IB isolates. Serology of the yolk and serum was carried out using haemagglutination (HI test and ELISA. Results: Yolk serology revealed a geometric mean titre of 415.9 and 15188±768 in HI test and ELISA respectively on 28 days post vaccination (dpv as against 16.0 and 1881±86 in yolk from unvaccinated hens. The HI test and ELISA indicated that the level of maternal antibody (MAb in the chicks obtained from vaccinated hens was significantly (P< 0.01 higher on seven days of age than that of chicks from unvaccinated hens. However, the level of Mab of the chicks obtained from vaccinated hens decreased to below the level of protection at two weeks of age. Wild isolate and another isolate obtained from different geographical area were used for challenge dividing the chicks from vaccinated and unvaccinated hens equally. Mortality was observed in the challenged chicks from vaccinated (one in heterologus challenge and unvaccinated (two hens. Examination of kidney specimens collected from dead chicks revealed mottling and severe congestion grossly and inflammatory, degenerative and necrotic changes microscopically. Conclusion: The partial cross-protection against heterologous challenge and incomplete protection against homologous challenge with wild isolates were noticed. [Vet World 2013; 6(3.000: 134-138
Wilson, J H; Hermann-Dekkers, W M
The significance of canine parvovirus (CPV) infections as a permanent threat susceptible dogs, in particular pups, made the authors develop three liquid homologous inactivated adjuvant CPV vaccines that were compatible with existing canine vaccines and could be incorporated in current vaccination programmes. On vaccine (Kavak Parvo) contained only the CPV component, the second product (Kavak i-LP) also contained two inactivated leptospiral antigens, and the third vaccine (Kavak i-HLP) contained in addition an inactivated canine hepatitis virus. This paper reports on the studies conducted to test the safety and efficacy of the three products. They were used as such and as diluents for freeze dried vaccines containing live attenuated measles, distemper, and hepatitis viruses. The study was performed in a breeding kennel where all dogs were free from CPV antibodies and the nonvaccinated sentinels remained so for the course of the study. All vaccines proved to be safe in dogs of all ages, including pregnant bitches. The efficacy of the CPV component was studied both by monitoring antibody titres for more than a year and by challenge exposure of some dogs to virulent CPV. The results obtained from these studies prove that the CPV component used in the three vaccines can be incorporated as indicated in the recommended canine vaccination programmes. The observations that the inactivated CPV and hepatitis components do induce an active immunity in pups that are still protected by low levels of maternally derived antibodies against these viruses, make those vaccines very suitable in breeding kennels. Additional studies on a comparative basis are being continued in edemically CPV infected breeding kennels to quantify the significance of these observations in these special conditions.
Liao, Guoyang; Li, Rongcheng; Li, Changgui; Sun, Mingbo; Jiang, Shude; Li, Yanping; Mo, Zhaojun; Xia, Jielai; Xie, Zhongping; Che, Yanchun; Yang, Jingsi; Yin, Zhifang; Wang, Jianfeng; Chu, Jiayou; Cai, Wei; Zhou, Jian; Wang, Junzhi; Li, Qihan
The development of a Sabin strain-based inactivated poliovirus vaccine (Sabin-IPV) is imperative to protecting against vaccine-associated paralytic poliomyelitis in developing countries. In this double-blinded, parallel-group, noninferiority trial, eligible infants aged 60-90 days were randomly assigned in a ratio of 1:1 to receive either 3 doses of Sabin-IPV or Salk strain-based IPV (Salk-IPV) at 30-day intervals and a booster at the age of 18 months. Immunogenicity and safety were assessed on the basis of a protocol. Of 1438 infants, 1200 eligible infants were recruited and received either Sabin-IPV or Salk-IPV. From the Sabin-IPV and Salk-IPV groups, 570 and 564 infants, respectively, completed the primary immunization and formed the per-protocol population. The seroconversion rates of the participants who received Sabin-IPV were 100%, 94.9%, and 99.0% (types I, II, and III, respectively), and those of the participants who received Salk-IPV were 94.7%, 91.3%, and 97.9% 1 month after the completion of primary immunization. An anamnestic response for poliovirus types I, II, and III was elicited by a booster in both groups. Except in the case of fever, other adverse events were similar between the 2 groups. The immune response induced by Sabin-IPV was not inferior to that established with Salk-IPV. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail email@example.com.
Pons-Salort, Margarita; Molodecky, Natalie A; O'Reilly, Kathleen M; Wadood, Mufti Zubair; Safdar, Rana M; Etsano, Andrew; Vaz, Rui Gama; Jafari, Hamid; Grassly, Nicholas C; Blake, Isobel M
Global withdrawal of serotype-2 oral poliovirus vaccine (OPV2) took place in April 2016. This marked a milestone in global polio eradication and was a public health intervention of unprecedented scale, affecting 155 countries. Achieving high levels of serotype-2 population immunity before OPV2 withdrawal was critical to avoid subsequent outbreaks of serotype-2 vaccine-derived polioviruses (VDPV2s). In August 2015, we estimated vaccine-induced population immunity against serotype-2 poliomyelitis for 1 January 2004-30 June 2015 and produced forecasts for April 2016 by district in Nigeria and Pakistan. Population immunity was estimated from the vaccination histories of children poliomyelitis. District immunity estimates were spatio-temporally smoothed using a Bayesian hierarchical framework. Coverage estimates for immunisation activities were also obtained, allowing for heterogeneity within and among districts. Forward projections of immunity, based on these estimates and planned immunisation activities, were produced through to April 2016 using a cohort model. Estimated population immunity was negatively correlated with the probability of VDPV2 poliomyelitis being reported in a district. In Nigeria and Pakistan, declines in immunity during 2008-2009 and 2012-2013, respectively, were associated with outbreaks of VDPV2. Immunity has since improved in both countries as a result of increased use of trivalent OPV, and projections generally indicated sustained or improved immunity in April 2016, such that the majority of districts (99% [95% uncertainty interval 97%-100%] in Nigeria and 84% [95% uncertainty interval 77%-91%] in Pakistan) had >70% population immunity among children poliomyelitis was forecasted to improve in April 2016 compared to the first half of 2015 in Nigeria and Pakistan. These analyses informed the endorsement of OPV2 withdrawal in April 2016 by the WHO Strategic Advisory Group of Experts on Immunization.
E M D L van der Heijden
Full Text Available Conventional control and eradication strategies for bovine tuberculosis (BTB face tremendous difficulties in developing countries; countries with wildlife reservoirs, a complex wildlife-livestock-human interface or a lack of veterinary and veterinary public health surveillance. Vaccination of cattle and other species might in some cases provide the only suitable control strategy for BTB, while in others it may supplement existing test-and-slaughter schemes. However, the use of live BCG has several limitations and the global rise of HIV/AIDS infections has furthermore warranted the exploration of inactivated vaccine preparations. The aim of this study was to compare the immune response profiles in response to parenteral vaccination with live BCG and two inactivated vaccine candidates in cattle. Twenty-four mixed breed calves (Bos taurus aged 4-6 months, were allocated to one of four groups and vaccinated sub-cutaneously with live M. bovis BCG (Danish 1331, formalin-inactivated M. bovis BCG, heat-killed M. bovis or PBS/Montanide™ (control. Interferon-γ responsiveness and antibody production were measured prior to vaccination and at weekly intervals thereafter for twelve weeks. At nine weeks post-priming, animals were skin tested using tuberculins and MTBC specific protein cocktails and subsequently challenged through intranodular injection of live M. bovis BCG. The animals in the heat-killed M. bovis group demonstrated strong and sustained cell-mediated and humoral immune responses, significantly higher than the control group in response to vaccination, which may indicate a protective immune profile. Animals in this group showed reactivity to the skin test reagents, confirming good vaccine take. Lastly, although not statistically significant, recovery of BCG after challenge was lowest in the heat-killed M. bovis group. In conclusion, the parenteral heat-killed M. bovis vaccine proved to be clearly immunogenic in cattle in the present study
Thomas R Hird
Full Text Available Inactivated poliovirus vaccine (IPV may be used in mass vaccination campaigns during the final stages of polio eradication. It is also likely to be adopted by many countries following the coordinated global cessation of vaccination with oral poliovirus vaccine (OPV after eradication. The success of IPV in the control of poliomyelitis outbreaks will depend on the degree of nasopharyngeal and intestinal mucosal immunity induced against poliovirus infection. We performed a systematic review of studies published through May 2011 that recorded the prevalence of poliovirus shedding in stool samples or nasopharyngeal secretions collected 5-30 days after a "challenge" dose of OPV. Studies were combined in a meta-analysis of the odds of shedding among children vaccinated according to IPV, OPV, and combination schedules. We identified 31 studies of shedding in stool and four in nasopharyngeal samples that met the inclusion criteria. Individuals vaccinated with OPV were protected against infection and shedding of poliovirus in stool samples collected after challenge compared with unvaccinated individuals (summary odds ratio [OR] for shedding 0.13 (95% confidence interval [CI] 0.08-0.24. In contrast, IPV provided no protection against shedding compared with unvaccinated individuals (summary OR 0.81 [95% CI 0.59-1.11] or when given in addition to OPV, compared with individuals given OPV alone (summary OR 1.14 [95% CI 0.82-1.58]. There were insufficient studies of nasopharyngeal shedding to draw a conclusion. IPV does not induce sufficient intestinal mucosal immunity to reduce the prevalence of fecal poliovirus shedding after challenge, although there was some evidence that it can reduce the quantity of virus shed. The impact of IPV on poliovirus transmission in countries where fecal-oral spread is common is unknown but is likely to be limited compared with OPV.
Monath, Thomas P; Fowler, Elizabeth; Johnson, Casey T; Balser, John; Morin, Merribeth J; Sisti, Maggie; Trent, Dennis W
Yellow fever is a lethal viral hemorrhagic fever occurring in Africa and South America. A highly effective live vaccine (17D) is widely used for travelers to and residents of areas in which yellow fever is endemic, but the vaccine can cause serious adverse events, including viscerotropic disease, which is associated with a high rate of death. A safer, nonreplicating vaccine is needed. In a double-blind, placebo-controlled, dose-escalation, phase 1 study of 60 healthy subjects between 18 and 49 years of age, we investigated the safety and immunogenicity of XRX-001 purified whole-virus, β-propiolactone-inactivated yellow fever vaccine produced in Vero cell cultures and adsorbed to aluminum hydroxide (alum) adjuvant. On two visits 21 days apart, subjects received intramuscular injections of vaccine that contained 0.48 μg or 4.8 μg of antigen. Levels of neutralizing antibodies were measured at baseline and on days 21, 31, and 42. The vaccine induced the development of neutralizing antibodies in 100% of subjects receiving 4.8 μg of antigen in each injection and in 88% of subjects receiving 0.48 μg of antigen in each injection. Antibody levels increased by day 10 after the second injection, at which time levels were significantly higher with the 4.8-μg formulation than with the 0.48-μg formulation (geometric mean titer, 146 vs. 39; Pvaccine groups than in the placebo group: mild pain, tenderness, and (much less frequently) itching at the injection site. One case of urticaria was observed on day 3 after the second dose of 4.8 μg of vaccine. A two-dose regimen of the XRX-001 vaccine, containing inactivated yellow fever antigen with an alum adjuvant, induced neutralizing antibodies in a high percentage of subjects. XRX-001 has the potential to be a safer alternative to live attenuated 17D vaccine. (Funded by Xcellerex; ClinicalTrials.gov number, NCT00995865.).
Wang, Yuhuan; Azevedo, Marli; Saif, Linda J; Gentsch, Jon R; Glass, Roger I; Jiang, Baoming
Live oral rotavirus vaccines that are effective in middle and high income countries have been much less immunogenic and effective among infants in resource-limited settings. Several hypotheses might explain this difference, including neutralization of the vaccine by high levels of maternal antibody in serum and breast milk, severe malnutrition, and interference by other flora and viruses in the gut. We have pursued development of an alternative parenteral rotavirus vaccine with the goal of inducing comparable levels of immunogenicity and efficacy in populations throughout the world regardless of their income levels. In the present study, we assessed the immunogenicity and protection of a candidate inactivated rotavirus vaccine (IRV), the human strain CDC-9 (G1P) formulated with aluminum phosphate, against rotavirus infection in gnotobiotic piglets. Three doses of IRV induced high titers of rotavirus-specific IgG and neutralizing activity in the sera of gnotobiotic piglets and protection against shedding of rotavirus antigen following oral challenge with a homologous virulent human strain Wa (G1P). Our findings demonstrate the proof of concept for an IRV in a large animal model and provide evidence and justification for further clinical development as an alternative candidate vaccine. Published by Elsevier Ltd.
Full Text Available Abstract Background There have been many efforts to develop efficient vaccines for the control of porcine reproductive and respiratory syndrome virus (PRRSV. Although inactivated PRRSV vaccines are preferred for their safety, they are weak at inducing humoral immune responses and controlling field PRRSV infection, especially when heterologous viruses are involved. Results In all groups, the sample to positive (S/P ratio of IDEXX ELISA and the virus neutralization (VN titer remained negative until challenge. While viremia did not reduce in the vaccinated groups, the IDEXX-ELISA-specific immunoglobulin G increased more rapidly and to significantly greater levels 7 days after the challenge in all the vaccinated groups compared to the non-vaccinated groups (p 6 PFU/mL PRRSV vaccine-inoculated and binary ethylenimine (BEI-inactivated groups 22 days after challenge (p Conclusions The inactivated vaccine failed to show the humoral immunity, but it showed different immune response after the challenge compared to mock group. Although the 106 PFU/mL-vaccinated and BEI-inactivated groups showed significantly greater VN titers 22 days after challenge, all the groups were already negative for viremia.
Thomassen, Y.E.; Oever, van 't A.G.; Oijen, van M.G.C.T.; Wijffels, R.H.; Pol, van der L.A.; Bakker, W.A.M.
Worldwide efforts to eradicate polio caused a tipping point in polio vaccination strategies. A switch from the oral polio vaccine, which can cause circulating and virulent vaccine derived polioviruses, to inactivated polio vaccines (IPV) is scheduled. Moreover, a manufacturing process, using
Shim, Eunha; Brown, Shawn T; DePasse, Jay; Nowalk, Mary Patricia; Raviotta, Jonathan M; Smith, Kenneth J; Zimmerman, Richard K
Prior studies showed that live attenuated influenza vaccine (LAIV) is more effective than inactivated influenza vaccine (IIV) in children aged 2-8 years, supporting the Centers for Disease Control and Prevention (CDC) recommendations in 2014 for preferential LAIV use in this age group. However, 2014-2015 U.S. effectiveness data indicated relatively poor effectiveness of both vaccines, leading CDC in 2015 to no longer prefer LAIV. An age-structured model of influenza transmission and vaccination was developed, which incorporated both direct and indirect protection induced by vaccination. Based on this model, the cost effectiveness of influenza vaccination strategies in children aged 2-8 years in the U.S. was estimated. The base case assumed a mixed vaccination strategy where 33.3% and 66.7% of vaccinated children aged 2-8 years receive LAIV and IIV, respectively. Analyses were performed in 2014-2015. Using published meta-analysis vaccine effectiveness data (83% LAIV and 64% IIV), exclusive LAIV use would be a cost-effective strategy when vaccinating children aged 2-8 years, whereas IIV would not be preferred. However, when 2014-2015 U.S. effectiveness data (0% LAIV and 15% IIV) were used, IIV was likely to be preferred. The cost effectiveness of influenza vaccination in children aged 2-8 years is highly dependent on vaccine effectiveness; the vaccine type with higher effectiveness is preferred. In general, exclusive IIV use is preferred over LAIV use, as long as vaccine effectiveness is higher for IIV than for LAIV. Copyright © 2016 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.
Thacker, Naveen; Thacker, Deep; Pathak, Ashish
Global Alliance for Vaccines and Immunization (GAVI, the Vaccine Alliance) is an international organization built through public-private partnership. GAVI has supported more than 200 vaccine introductions in the last 5 years by financing major proportion of costs of vaccine to 73 low-income countries using a co-financing model. GAVI has worked in close co-ordination with Global Polio Eradication Initiative (GPEI) since 2013, to strengthen health systems in countries so as to accelerate introduction of inactivated polio vaccine (IPV). GAVI is involved in many IPV related issues like demand generation, supply, market shaping, communications, country readiness etc. Most of the 73 GAVI eligible countries are also high priority countries for GPEI. GAVI support has helped India to accelerate introduction of IPV in all its states. However, GAVI faces challenges in IPV supply-related issues in the near future. It also needs to play a key role in global polio legacy planning and implementation.
Sluijs, van der M.T.W.; Schroer-Joosten, D.P.H.; Fid-Fourkour, A.; Vrijenhoek, M.; Debyser, I.; Gregg, D.A.; Dufe, D.M.; Moulin, V.; Moormann, R.J.M.; Smit, de A.J.
The effect of vaccination with a commercial inactivated Bluetongue virus serotype 8 (BTV-8) vaccine on the ability of BTV-8 to cross the ruminant placenta was investigated in two experiments. Ten pregnant ewes (Experiment 1) or heifers (Experiment 2) were vaccinated according to the manufacturer's
Kraan, Heleen; Soema, Peter; Amorij, Jean-Pierre; Kersten, Gideon
Polio is on the brink of eradication. Improved inactivated polio vaccines (IPV) are needed towards complete eradication and for the use in the period thereafter. Vaccination via mucosal surfaces has important potential advantages over intramuscular injection using conventional needle and syringe, the currently used delivery method for IPV. One of them is the ability to induce both serum and mucosal immune responses: the latter may provide protection at the port of virus entry. The current study evaluated the possibilities of polio vaccination via mucosal surfaces using IPV based on attenuated Sabin strains. Mice received three immunizations with trivalent sIPV via intramuscular injection, or via the intranasal or sublingual route. The need of an adjuvant for the mucosal routes was investigated as well, by testing sIPV in combination with the mucosal adjuvant cholera toxin. Both intranasal and sublingual sIPV immunization induced systemic polio-specific serum IgG in mice that were functional as measured by poliovirus neutralization. Intranasal administration of sIPV plus adjuvant induced significant higher systemic poliovirus type 3 neutralizing antibody titers than sIPV delivered via the intramuscular route. Moreover, mucosal sIPV delivery elicited polio-specific IgA titers at different mucosal sites (IgA in saliva, fecal extracts and intestinal tissue) and IgA-producing B-cells in the spleen, where conventional intramuscular vaccination was unable to do so. However, it is likely that a mucosal adjuvant is required for sublingual vaccination. Further research on polio vaccination via sublingual mucosal route should include the search for safe and effective adjuvants, and the development of novel oral dosage forms that improve antigen uptake by oral mucosa, thereby increasing vaccine immunogenicity. This study indicates that both the intranasal and sublingual routes might be valuable approaches for use in routine vaccination or outbreak control in the period after
Full Text Available Introduction: Polio vaccination rates remain low in certain regions of Malaysia. The Federal Territory of Kuala Lumpur (FTKL reported coverage of only 29.3% in 2005 and 61.2% in 2006, despite a Department of Health campaign to provide free three-round immunizations. The estimated numbers of live births used to calculate these rates may have artificially lowered the reported coverage percentages.Methods: A descriptive, cross-sectional household survey was conducted throughout the FTKL in 2007 to assess the actual polio vaccination status of children aged 9 to 24 months. Minimum sample size was calculated and proportionately divided among the 11 FTKL parliamentary constituencies. Residential areas were then randomly selected for in-person interviews. We used the gathered information, verified by medical records, to calculate the actual vaccination coverage and to compare the rates determined by using estimated or registered live births for the region.Results: Of the 1713 study participants, 98.3% had completed their polio vaccination schedule. Only 21 children had been partially vaccinated, and nine children were completely unvaccinated. FTKL residents had 20 431 live births registered for 2006, as opposed to the official estimate of 28 400. When the registered value of live births was used to calculate vaccination coverage, the 2006 coverage increased (to 85.1%.Conclusion: Actual vaccination coverage in Kuala Lumpur was much higher than the estimated coverage previously reported, reflecting the expected success of the Department of Health immunization campaign. Estimated values of live births are insufficient to accurately determine vaccine status and should be avoided.
Pereira, Renata C; Silva, Andrea N M R; Souza, Marta Cristina O; Silva, Marlon V; Neves, Patrícia P C C; Silva, Andrea A M V; Matos, Denise D C S; Herrera, Miguel A O; Yamamura, Anna M Y; Freire, Marcos S; Gaspar, Luciane P; Caride, Elena
Yellow fever is an acute infectious disease caused by prototype virus of the genus Flavivirus. It is endemic in Africa and South America where it represents a serious public health problem causing epidemics of hemorrhagic fever with mortality rates ranging from 20% to 50%. There is no available antiviral therapy and vaccination is the primary method of disease control. Although the attenuated vaccines for yellow fever show safety and efficacy it became necessary to develop a new yellow fever vaccine due to the occurrence of rare serious adverse events, which include visceral and neurotropic diseases. The new inactivated vaccine should be safer and effective as the existing attenuated one. In the present study, the immunogenicity of an inactivated 17DD vaccine in C57BL/6 mice was evaluated. The yellow fever virus was produced by cultivation of Vero cells in bioreactors, inactivated with β-propiolactone, and adsorbed to aluminum hydroxide (alum). Mice were inoculated with inactivated 17DD vaccine containing alum adjuvant and followed by intracerebral challenge with 17DD virus. The results showed that animals receiving 3 doses of the inactivated vaccine (2 μg/dose) with alum adjuvant had neutralizing antibody titers above the cut-off of PRNT50 (Plaque Reduction Neutralization Test). In addition, animals immunized with inactivated vaccine showed survival rate of 100% after the challenge as well as animals immunized with commercial attenuated 17DD vaccine. Copyright © 2015 Elsevier Ltd. All rights reserved.
Full Text Available Bovine ephemeral fever (BEF is an economically important viral vector-borne cattle disease. Several live-attenuated, inactivated and recombinant vaccines have been tested, demonstrating varying efficacy. However, to the best of our knowledge, duration of immunity conferred by an inactivated vaccine has never been reported. In the last decade, Israel has faced an increasing number of BEF outbreaks. The need for an effective vaccine compatible with strains circulating in the Middle East region led to the development of a MONTANIDE™ ISA 206 VG (water-in-oil-in-water, inactivated vaccine based on a local strain. We tested the safety, immunogenicity and duration of immunity conferred by this vaccine. The induced neutralizing antibody (NA response was followed for 493 days in 40 cows vaccinated by different protocols. The vaccine did not cause adverse reactions or a decrease in milk production. All cows [except 2 (6.7% which did not respond to vaccination] showed a significant rise in NA titer of up to 1:256 following the second, third or fourth booster vaccination. Neutralizing antibody levels declined gradually to 1:16 up to 120 days post vaccination. This decline continued in cows vaccinated only twice, whereas cows vaccinated 3 or 4 times showed stable titers of approximately 1:16 for up to 267 days post vaccination. At least three vaccinations with the inactivated BEF vaccine were needed to confer long-lasting immunity. These results may have significant implications for the choice of vaccination protocol with inactivated BEF vaccines. Complementary challenge data should however be added to the above results in order to determine what is the minimal NA response conferring protection from clinical disease.
Aaby, Peter; Knudsen, K; Whittle, H
In an urban area of Guinea-Bissau, 384 children were enrolled in a randomized trial comparing morbidity and mortality rates after receiving high-titer Edmonston-Zagreb (EZ) measles vaccine administered from 4 months of age, with a control group receiving inactivated poliomyelitis vaccine at 4...
Infection with poliovirus (a small, non-enveloped Picornavirus) can result in poliomyelitis, hallmarked by symptoms of paralysis which is caused by viral destruction of motor neurons. Circulating humoral neutralizing antibodies can effectively protect against the disease, an immune response which
Inactivated poliovirus vaccine (IPV) plays an instrumental role in the Global Poliovirus Eradication Initiative (GPEI). The quality of IPV is controlled by assessment of the potency of vaccine batches. The potency of IPV can be assessed by both in vivo and in vitro methods. In vitro potency assessment is based upon the assessment of the quantity of the D-Antigen (D-Ag) units in an IPV. The D-Ag unit is used as a measure of potency as it is largely expressed on native infectious virions and is the protective immunogen. The most commonly used in vitro test is the indirect ELISA which is used to ensure consistency throughout production.A range of in vivo assays have been developed in monkeys, chicks, guinea pigs, mice, and rats to assess the potency of IPV. All are based on assessment of the neutralizing antibody titer within the sera of the respective animal model. The rat potency test has become the favored in vivo potency test as it shows minimal variation between laboratories and the antibody patterns of rats and humans are similar. With the development of transgenic mice expressing the human poliovirus receptor, immunization-challenge tests have been developed to assess the potency of IPVs. This chapter describes in detail the methodology of these three laboratory tests to assess the quality of IPVs.
I.K.G. Visser (Ilona); M.W.G. van de Bildt (Marco); H.N. Brugge; P.J.H. Reijnders; E.J. Vedder (Lies); J. Kuiper; P. de Vries (Petra); J. Groen (Jan); H.C. Walvoort; F.G.C.M. Uytdehaag (Fons); A.D.M.E. Osterhaus (Albert)
textabstractTwo inactivated canine distemper virus (CDV) vaccines--an adjuvanted whole inactivated virus and a subunit ISCOM preparation--were tested for their ability to induce protective immunity in harbour seals (Phoca vitulina) against phocid distemper, a disease that recently killed greater
Mahamud, Abdirahman; Kamadjeu, Raoul; Webeck, Jenna; Mbaeyi, Chukwuma; Baranyikwa, Marie Therese; Birungi, Julianne; Nurbile, Yassin; Ehrhardt, Derek; Shukla, Hemant; Chatterjee, Anirban; Mulugeta, Abraham
After the last case of type 1 wild poliovirus (WPV1) was reported in 2007, Somalia experienced another outbreak of WPV1 (189 cases) in 2013. We conducted a retrospective, matched case-control study to evaluate the vaccine effectiveness (VE) of oral polio vaccine (OPV). We retrieved information from the Somalia Surveillance Database. A case was defined as any case of acute flaccid paralysis (AFP) with virological confirmation of WPV1. We selected two groups of controls for each case: non-polio AFP cases ("NPAFP controls") matched to WPV1 cases by age, date of onset of paralysis and region; and asymptomatic "neighborhood controls," matched by age. Using conditional logistic regression, we estimated the VE of OPV as (1-odds ratio)×100. We matched 99 WPV cases with 99 NPAFP controls and 134 WPV1 cases with 268 neighborhood controls. Using NPAFP controls, the overall VE was 70% (95% confidence interval [CI], 37-86), 59% (2-83) among 1-3 dose recipients, 77% (95% CI, 46-91) among ≥4 dose recipients. In neighborhood controls, the overall VE was 95% (95% CI, 84-98), 92% (72-98) among 1-3 dose recipients, and 97% (89-99) among ≥4 dose recipients. When the analysis was limited to cases and controls ≤24 months old, the overall VE in NPAFP and neighborhood controls was 95% (95% CI, 65-99) and 97% (95% CI, 76-100), respectively. Among individuals who were fully vaccinated with OPV, vaccination was effective at preventing WPV1 in Somalia. Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.
Stuurman, Anke L.; Marano, Cinzia; Bunge, Eveline M.; De Moerlooze, Laurence; Shouval, Daniel
ABSTRACT The WHO recommends integration of universal mass vaccination (UMV) against hepatitis A virus (HAV) in national immunization schedules for children aged ≥1 year, if justified on the basis of acute HAV incidence, declining endemicity from high to intermediate and cost-effectiveness. This recommendation has been implemented in several countries. Our aim was to assess the impact of UMV using monovalent inactivated hepatitis A vaccines on incidence and persistence of anti-HAV (IgG) antibodies in pediatric populations. We conducted a systematic review of literature published between 2000 and 2015 in PubMed, Cochrane Library, LILACS, IBECS identifying a total of 27 studies (Argentina, Belgium, China, Greece, Israel, Panama, the United States and Uruguay). All except one study showed a marked decline in the incidence of hepatitis A post introduction of UMV. The incidence in non-vaccinated age groups decreased as well, suggesting herd immunity but also rising susceptibility. Long-term anti-HAV antibody persistence was documented up to 17 y after a 2-dose primary vaccination. In conclusion, introduction of UMV in countries with intermediate endemicity for HAV infection led to a considerable decrease in the incidence of hepatitis A in vaccinated and in non-vaccinated age groups alike. PMID:27786671
Ma, Yan; Qin, Min; Hu, Hui-Qiong; Ji, Guang; Feng, Ling; Gao, Na; Gu, Jie; Xie, Bing-Feng; He, Ji-Hong; Sun, Ming-Bo
In order to search the preparation process and optimazing dosage ratio of adsorbed diphtheria-tetanus-acellular pertussis and sabin inactivated poliovirus combined vaccine (DTaP-sIPV), the neutralizing antibody titers of IPV induced by different concentration of DTaP-sIPV were investigated on rats. Two batches of DTaP-sLPV were produced using different concentration of sIPV and the quality control was carried. Together with sabin-IPV and DTaP-wIPV ( boostrix-polio, GSK, Belgium) as control group, the DTaP-sIPV were administrated on three-dose schedule at 0, 1, 2 month on rats. Serum sample were collected 30 days after each dose and neutralizing antibody titers against three types poliovirus were determined using micro-neutralization test. Two batches of prepared DTaP-sIPV and control sLPV were according to the requirement of Chinese Pharmacopoeia (Volume III, 2005 edition) and showed good stability. The seropositivity rates were 100% for sabin inactivated poliovirus antigen in all groups. The GMTs (Geometric mean titers) of neutralizing antibodies against three types poliovirus increased. The prepared DTaP-sIPV was safe, stable and effective and could induced high level neutralizing antibody against poliovirus on rats.
N. F. Snegova
Full Text Available The article summarizes data on methods and opportunities of frequently ailing children rehabilitation. Authors mark a leading role of vaccination against pneumotropic infections. Questions of successful interaction between doctor and frequently ailing child’s parents are highlighted. The observation of 94 children 3 months — 3 years old (patients had different types of initial immune insuffiiency, neurological pathology, recurrent obstructive bronchitis, or were included in group of frequently ailing children vaccinated with Pentaxim was performed. 94% of children showed asymptomatic postvaccinal period. Fever up to 39°C occurred in 2.3% of patients. Local reactions (diameter was not over 3–5 cm developed in 1.7% of children. There was no any case of postvaccinal complication. Evaluation of vaccine’s reactogenity proves its safety and reasonability in immunization against pertussis, diphtheria, tetanus, poliomyelitis, Haemophilis influenzae type b in children of different health state including those with concomitant diseases.
Francisco Bustos M.
Full Text Available Three groups of 25 broilers were vaccinated on two opportunities by aerosol using inactivated NC (Newcastle virus and different helper concentrations of porinas (20 ìg, 50 ìg, 125 ìg. A fourth group was injected with live B1 virus (12 and 28 days of age nasally. The NC inactivated virus (La Sota strain was concentrated 10 times with PEG with a final titer of 1:2.056. Twenty serums for each group were taken in order to evaluate NC antibodies using the HI and double immuno-difusion tests for IgA detection at 1, 12, 28 and 42 days of age. During the study the chickens were on a restricted diet in order to control ascites (2.640 mosl. On day 42, two broilers of the fourth group (live virus presented ascites and 1 broiler of group 1 presented lung edema (20 ìg. The geometric mean for NC antibodies titers at 42 days of age was 2 in the groups 1,2,3 and 5.7 in the group 4 (Log 2. For IgA, 180 mg/dl, 135 mg/dl, 120 mg/dl and 176 mg/dl respectively. Three broilers of each group were challenged with a pathogenic strain of NC, at 42 day of age, without signs of disease after 72 hours when the positive control group was dead. Gross and microscopic lesions were not detected in the bursa of Fabricius or thymo. [thymo sounds like short hand for something that should be properly named.] Very good animal weight, conversion and efficiency results were observed in all the groups. New studies using a fixed dose of porinas, larger numbers of broilers and the establishment of protective levels of IgA against NC challenge are recommended.
AWARD NUMBER: W81XWH-16-2-0032 TITLE: Systems Biology of Immune Response to Live and Inactivated Dengue Virus Vaccines PRINCIPAL INVESTIGATOR...CONTRACT NUMBER Systems Biology of Immune Response to Live and Inactivated Dengue Virus Vaccines 5b. GRANT NUMBER W81XWH-16-2-0032 5c. PROGRAM ELEMENT...cell) responses will be measured using molecular and cellular approaches and the data analyzed using a systems biology approach. During the first
AWARD NUMBER: W81XWH-16-2-0031 TITLE: Systems Biology of the Immune Response to Live and Inactivated Dengue Virus Vaccines PRINCIPAL...SUBTITLE 5a. CONTRACT NUMBER Systems Biology of the Immune Response to Live and Inactivated Dengue Virus Vaccines 5b. GRANT NUMBER W81XWH-16-2-0031 5c...adaptive (T and B cell) responses will be measured using molecular and cellular approaches and the data analyzed using a systems biology approach
Theeten, H.; Rumke, H.C.; Hoppener, F.J.; Vilatimo, R.; Narejos, S.; Damme, P. van; Hoet, B.
OBJECTIVE: To evaluate immunogenicity and reactogenicity of primary vaccination with reduced-antigen-content diphtheria-tetanus-acellular pertussis (dTpa) or dTpa-inactivated poliovirus (dTpa-IPV) vaccine compared to diphtheria-tetanus-toxoid vaccines (Td) in adults > or = 40 years of age without
Lelie, P. N.; Reesink, H. W.; Lucas, C. J.
The efficacy of two heating cycles (90 sec at 103 degrees C and 10 hr at 65 degrees C) used during manufacture of a plasma-derived hepatitis-B vaccine was validated for the inactivation of 12 virus families. A period of 15 min warming up to 65 degrees C had already completely inactivated
Billah, Mallick M; Zaman, K; Estivariz, Concepcion F; Snider, Cynthia J; Anand, Abhijeet; Hampton, Lee M; Bari, Tajul I A; Russell, Kevin L; Chai, Shua J
Introduction of inactivated polio vaccine creates challenges in maintaining the cold chain for vaccine storage and distribution. We evaluated the cold chain in 23 health facilities and 36 outreach vaccination sessions in 8 districts and cities of Bangladesh, using purposive sampling during August-October 2015. We interviewed immunization and cold-chain staff, assessed equipment, and recorded temperatures during vaccine storage and transportation. All health facilities had functioning refrigerators, and 96% had freezers. Temperature monitors were observed in all refrigerators and freezers but in only 14 of 66 vaccine transporters (21%). Recorders detected temperatures >8°C for >60 minutes in 5 of 23 refrigerators (22%), 3 of 6 cold boxes (50%) transporting vaccines from national to subnational depots, and 8 of 48 vaccine carriers (17%) used in outreach vaccination sites. Temperatures cold boxes (21%) transporting vaccine from subnational depots to health facilities and 14 of 48 vaccine carriers (29%). Bangladesh has substantial cold-chain storage and transportation capacity after inactivated polio vaccine introduction, but temperature fluctuations during vaccine transport could cause vaccine potency loss that could go undetected. Bangladesh and other countries should strive to ensure consistent and sufficient cold-chain storage and monitor the cold chain during vaccine transportation at all levels. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.
Teng, Qiaoyang; Shen, Weixia; Liu, Qinfang; Rong, Guangyu; Chen, Lin; Li, Xuesong; Chen, Hongjun; Yang, Jianmei; Li, Zejun
Wild ducks play an important role in the evolution of avian influenza viruses (AIVs). Domestic ducks in China are known to carry and spread H9N2 AIVs that are thought to have contributed internal genes for the recent outbreak of zoonotic H7N9 virus. In order to protect animal and public health, an effective vaccine is urgently needed to block and prevent the spread of H9N2 virus in ducks. We developed an inactivated H9N2 vaccine (with adjuvant Montanide ISA 70VG) based on an endemic H9N2 AIV and evaluated this vaccine in ducks. The results showed that the inactivated H9N2 vaccine was able to induce a strong and fast humoral immune response in vaccinated ducks. The hemagglutination inhibition titer in the sera increased fast, and reached its peak of 12.3 log2 at 5 weeks post-vaccination in immunized birds and remained at a high level for at least 37 weeks post-vaccination. Moreover, viral shedding was completely blocked in vaccinated ducks after challenge with a homologous H9N2 AIV at both 3 and 37 weeks post-vaccination. The results of this study indicate that the inactivated H9N2 vaccine induces high and prolonged immune response in vaccinated ducks and are efficacious in protecting ducks from H9N2 infection.
Zanolari, P; Bruckner, L; Fricker, R; Kaufmann, C; Mudry, M; Griot, C; Meylan, M
Bluetongue virus serotype 8 (BTV-8) has caused disease in domestic ruminants in several countries of northern Europe since 2006. In 2008 a mass-vaccination program was launched in most affected countries using whole virus inactivated vaccines. To evaluate 2 inactivated vaccines (Bovilis BTV 8; BTVPUR AlSap8) for immunogenicity and safety against BTV-8 in South American camelids (SAC) in a field trial. Forty-two SAC (25 Alpacas, 17 Llamas) aged between 1 and 16 years. The animals were vaccinated twice at intervals of 21 days. They were observed clinically for adverse local, systemic, or both reactions throughout the trial. Blood samples collected on days 0, 14, 21, 43, and 156 after vaccination were tested for the presence of BTV-8 virus by real time-polymerase chain reaction and of specific antibodies by competitive ELISA and a serum neutralization test. All vaccinated animals developed antibodies to BTV-8 after the 2nd administration of the vaccine. No adverse effects were observed except for moderate local swellings at the injection site, which disappeared within 21 days. Slightly increased body temperatures were only observed in the first 2 days after vaccination. The BTV was not detected in any of the samples analyzed. The administration of the 2 inactivated commercial vaccines was safe and induced seroconversion against BTV-8 in all vaccinated animals. The results of this study suggest that 2 doses injected 3 weeks apart is a suitable vaccination regimen for SAC.
Schwick, H G
At a meeting of the Royal and Imperial Association of Physicians in Vienna on December 18, 1908 Dr. Karl Landsteiner reported on the successful experimental transmission of poliomyelitis from man to ape in a study which he undertook together with Erwin Popper. In a scientific article that was published shortly after the meeting, Landsteiner wrote that "the poliomyelitis virus belongs to the group of filterable micro-organisms". Soon, Landsteiner's results were confirmed by other colleagues. During a congress in Washington 1912 Landsteiner declared that the development of a vaccine against poliomyelitis might prove difficult but was certainly possible in his opinion. It took another 45 years before the first polio vaccine was available (1955 Salk) and another 5 years until the oral vaccine (1960 Sabin) was implemented. The incidence of poliomyelitis decreased dramatically in industrial countries as a result of vaccination. Today, poliomyelitis is still an enormous threat in developing countries. Together with many national and international institutions the WHO fights this situation very hard by means of vaccination campaigns. The incidence of side effects and insufficient reactions is small with both vaccines. New techniques in the field of molecular biology and a good knowledge of the poliovirus make it likely that further improvements on the vaccines which are currently available will take place.
Monath, Thomas P; Lee, Cynthia K; Julander, Justin G; Brown, Alicja; Beasley, David W; Watts, Douglas M; Hayman, Edward; Guertin, Patrick; Makowiecki, Joseph; Crowell, Joseph; Levesque, Philip; Bowick, Gavin C; Morin, Merribeth; Fowler, Elizabeth; Trent, Dennis W
In the last 10 years new concerns have arisen about safety of the live, attenuated yellow fever (YF) 17D vaccine, in particular viscerotropic adverse events, which have a case-fatality rate of 64%. A non-replicating cell culture-based vaccine would not cause these adverse events, and potentially could be used in persons with precautions or contraindications to use of the live vaccine, including age 60 years, egg allergy, immune suppression, and pregnancy. We developed a whole virion vaccine from the 17D strain inactivated with beta-propiolactone, and adsorbed to aluminum hydroxide. The inactivated vaccine was highly immunogenic in mice, hamsters, and cynomolgus macaques. After a single dose in hamsters and macaques, neutralizing antibody titers were similar to those elicited by the live 17D vaccine (YF-VAX, Sanofi Pasteur). After two doses of inactivated vaccine, neutralizing antibody titers in hamsters were significantly higher than after a single dose of YF-VAX [geometric mean titer (GMT) 20,480 vs. 1940, respectively (Pvaccine or a single dose of YF-VAX were fully protected against hepatitis, viremia, weight loss and death after challenge with YF virus (Jimenez strain). A clinical trial of the inactivated vaccine (XRX-001) has been initiated. Copyright 2010 Elsevier Ltd. All rights reserved.
Audouy, Sandrine A.L.; van der Schaaf, Gieta; Hinrichs, Wouter L.J.; Frijlink, Henderik W.; Wilschut, Jan; Huckriede, Anke
Stabilization and ease of administration are two ways to substantially improve the use of current vaccines. In the present study an influenza whole inactivated virus (WIV) vaccine was freeze-dried or spray-freeze dried in the presence of inulin as a cryoprotectant. Only spray-freeze drying rendered
Fedorova, Antonina A; Goncharova, Elena P; Kovpak, Mikhail P; Vlassov, Valentin V; Zenkova, Marina A
The inactivation of viral particles with agents causing minimal damage to the structure of surface epitopes is a well-established approach for the production of killed virus vaccines. Here, we describe new agents for the inactivation of influenza virus, artificial ribonucleases (aRNases), which are chemical compounds capable of cleaving RNA molecules. Several aRNases were identified, exhibiting significant virucidal activity against the influenza A virus and causing a minimal effect on the affinity of monoclonal antibodies for the inactivated virus. Using a murine model of the influenza virus infection, a high protective activity of the aRNase-inactivated virus as a vaccine was demonstrated. The results of the experiments demonstrate the efficacy of novel chemical agents in the preparation of vaccines against influenza and, perhaps, against other infections caused by RNA viruses. Copyright © 2012 Elsevier Ltd. All rights reserved.
Fernanda de Costa
Full Text Available Inactivated polio vaccines (IPV have an important role at the final stages of poliomyelitis eradication programs, reducing the risks associated with the use of attenuated polio vaccine (OPV. An affordable option to enhance vaccine immunogenicity and reduce costs of IPV may be the use of an effective and renewable adjuvant. In the present study, the adjuvant activity of aqueous extract (AE and saponin fraction QB-90 from Quillaja brasiliensis using poliovirus antigen as model were analyzed and compared to a preparation adjuvanted with Quil-A, a well-known saponin-based commercial adjuvant. Experimental vaccines were prepared with viral antigen plus saline (control, Quil-A (50 µg, AE (400 µg or QB-90 (50 µg. Sera from inoculated mice were collected at days 0, 28, 42 and 56 post-inoculation of the first dose of vaccine. Serum levels of specific IgG, IgG1 and IgG2a were significantly enhanced by AE, QB-90 and Quil-A compared to control group on day 56. The magnitude of enhancement was statistically equivalent for QB-90 and Quil-A. The cellular response was evaluated through DTH and analysis of IFN-γ and IL-2 mRNA levels using in vitro reestimulated splenocytes. Results indicated that AE and QB-90 were capable of stimulating the generation of Th1 cells against the administered antigen to the same extent as Quil-A. Mucosal immune response was enhanced by the vaccine adjuvanted with QB-90 as demonstrated by increases of specific IgA titers in bile, feces and vaginal washings, yielding comparable or higher titers than Quil-A. The results obtained indicate that saponins from Q. brasiliensis are potent adjuvants of specific cellular and humoral immune responses and represent a viable option to Quil-A.
A.N. Mironov; A.A. Romanova; R.Ya. Meshkova; I.V. Fel’dblyum; N.V. Kupina; D.S. Bushmenkov; A.A. Tsaan
NPO «Microgen» developed vaccine «PANDEFLU» — influenza inactivated subunit adsorbed monovalent vaccine, strain A/California/7/2009 (H1N1), for specific prophylaxis of pandemic influenza in different age groups of citizens. Reactogenicity, safety and immunogenicity were analyzed in a study of volunteers 18–60 years old. The article presents results of administration of vaccine «PANDEFLU» in children. The study performed in two clinical centers proves good tolerability, reactogenicity, safety ...
Barrett, P Noel; Terpening, Sara J; Snow, Doris; Cobb, Ronald R; Kistner, Otfried
Rapid development and production of vaccines against emerging diseases requires well established, validated, robust technologies to allow industrial scale production and accelerated licensure of products. Areas covered: A versatile Vero cell platform has been developed and utilized to deliver a wide range of candidate and licensed vaccines against emerging viral diseases. This platform builds on the 35 years' experience and safety record with inactivated whole virus vaccines such as polio vaccine. The current platform has been optimized to include a novel double inactivation procedure in order to ensure a highly robust inactivation procedure for novel emerging viruses. The utility of this platform in rapidly developing inactivated whole virus vaccines against pandemic (-like) influenza viruses and other emerging viruses such as West Nile, Chikungunya, Ross River and SARS is reviewed. The potential of the platform for development of vaccines against other emerging viruses such as Zika virus is described. Expert commentary: Use of this platform can substantially accelerate process development and facilitate licensure because of the substantial existing data set available for the cell matrix. However, programs to provide vaccines against emerging diseases must allow alternative clinical development paths to licensure, without the requirement to carry out large scale field efficacy studies.
This study provides the first robust data that the antibody response of dogs vaccinated with Nobivac® Rabies vaccine stored for several months at high temperatures (up to 30 °C) is not inferior to that of dogs vaccinated with vaccine stored under recommended cold-chain conditions (2 - 8 °C). A controlled and randomized ...
Full Text Available NPO «Microgen» developed vaccine «PANDEFLU» — influenza inactivated subunit adsorbed monovalent vaccine, strain A/California/7/2009 (H1N1, for specific prophylaxis of pandemic influenza in different age groups of citizens. Reactogenicity, safety and immunogenicity were analyzed in a study of volunteers 18–60 years old. The article presents results of administration of vaccine «PANDEFLU» in children. The study performed in two clinical centers proves good tolerability, reactogenicity, safety and high immunogenicity of this vaccine.Key words: children, influenza, influenza virus А/H1N1, inactivated influenza vaccine, reactogenicity, safety, immunogenicity.(Voprosy sovremennoi pediatrii — Current Pediatrics. – 2010;9(4:106-109
Basu, R N
Poliomyelitis, an acute infectious disease which chiefly affects the central nervous system, is included in the list of 20 communicable diseases which are to be reported monthly by all institutions to the State Bureau of Health Intelligence for onward transmission to India's Central Bureau of Health Intelligence (CBHI). The reported number of 17,441 cases of poliomyelitis (annual average) since 1974 fail to reflect the magnitude of the problem in India. Directorate General of Health Services (DHGS) in collaboration with the State health authorities organized sample lameness surveys of children 5-9 years in the community during 1981-82. Poliomyelitis was found to be the major cause of lameness in children 5-9 years (64.5%). Data on admission of poliomyelitis cases from selected hospital in metropolitan cities were collected. All the hospitals reported maximum number of polio cases (more than 78%) below the age of 2 years. This data reinforce the importance of improving vaccination coverage in the age group most affected. High incidence of poliomyelitis (45% of the cases) were observed during July, August, and September, corresponding to the well demarcated monsoon season. This suggests a need to intensify immunization coverage during the low polio incidence period, namely, November to April. Polio vaccine was introduced in the national immunization program in 1980. The schedule recommends 3 doses of oral polio vaccine (OPV), starting from the age of 3 months with intervals not less than 1 month. DPT and polio vaccine are administered to the child at the same time. 1 booster dose of OPV is recommended 12-18 months later. The live attenuated OPV, not produced in India is used in the national program. The requirement of the program is met by import of bulk concentrated vaccine separately for type 1, type 2, and type 3. Then, it is diluted, blended, and ampouled by Haffkine Biopharmaceutical Corporation, Ltd. The recent visit of Dr. Jonas Salk has raised the issue of
Troy, Stephanie B; Kouiavskaia, Diana; Siik, Julia; Kochba, Efrat; Beydoun, Hind; Mirochnitchenko, Olga; Levin, Yotam; Khardori, Nancy; Chumakov, Konstantin; Maldonado, Yvonne
Inactivated polio vaccine (IPV) is necessary for global polio eradication because oral polio vaccine can rarely cause poliomyelitis as it mutates and may fail to provide adequate immunity in immunocompromised populations. However, IPV is unaffordable for many developing countries. Intradermal IPV shows promise as a means to decrease the effective dose and cost of IPV, but prior studies, all using 20% of the standard dose used in intramuscular IPV, resulted in inferior antibody titers. We randomly assigned 231 adults with well-controlled human immunodeficiency virus infection at a ratio of 2:2:2:1 to receive 40% of the standard dose of IPV intradermally, 20% of the standard dose intradermally, the full standard dose intramuscularly, or 40% of the standard dose intramuscularly. Intradermal vaccination was done using the NanoPass MicronJet600 microneedle device. Baseline immunity was 87%, 90%, and 66% against poliovirus serotypes 1, 2, and 3, respectively. After vaccination, antibody titers increased a median of 64-fold. Vaccine response to 40% of the standard dose administered intradermally was comparable to that of the standard dose of IPV administered intramuscularly and resulted in higher (although not significantly) antibody titers. Intradermal administration had higher a incidence of local side effects (redness and itching) but a similar incidence of systemic side effects and was preferred by study participants over intramuscular administration. A 60% reduction in the standard IPV dose without reduction in antibody titers is possible through intradermal administration. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: firstname.lastname@example.org.
Swayne, D E; Beck, J R; Garcia, M; Stone, H D
The influence of vaccine strain and antigen mass on the ability of inactivated avian influenza (AI) viruses to protect chicks from a lethal, highly pathogenic (HP) AI virus challenge was studied. Groups of 4-week-old chickens were immunized with inactivated vaccines containing one of 10 haemagglutinin subtype H5 AI viruses, one heterologous H7 AI virus or normal allantoic fluid (sham), and challenged 3 weeks later by intra-nasal inoculation with a HP H5 chicken-origin AI virus. All 10 H5 vaccines provided good protection from clinical signs and death, and produced positive serological reactions on agar gel immunodiffusion and haemagglutination inhibition tests. In experiment 1, challenge virus was recovered from the oropharynx of 80% of chickens in the H5 vaccine group. In five H5 vaccine groups, challenge virus was not recovered from the cloaca of chickens. In the other five H5 vaccine groups, the number of chickens with detection of challenge virus from the cloaca was lower than in the sham group (P turkey/Wisconsin/68 (H5N9) was the best vaccine candidate of the H5 strains tested (PD50= 0.006 μg AI antigen). These data demonstrate that chickens vaccinated with inactivated H5 whole virus AI vaccines were protected from clinical signs and death, but usage of vaccine generally did not prevent infection by the challenge virus, as indicated by recovery of virus from the oropharynx. Vaccine use reduced cloacal detection rates, and quantity of virus shed from the cloaca and oropharynx in some vaccine groups, which would potentially reduce environmental contamination and disease transmission in the field.
Two different types of vaccines were developed against poliomyelitis: The Salk vaccine using inactivated virus and the Sabin one, that was used later, after investigations assured its safety. The first one was made in Mexico with its own resources since 1957 thanks to the efforts of young researchers and technicians coordinated by Luis Gutiérrez-Villegas, M.D., who was a Clinical Pathologist, University Professor and President of the Mexican National Academy of Mexico. Copyright: © 2017 SecretarÍa de Salud.
Full Text Available Newcastle disease (ND is one of the most important diseases that affect birds; the epizootic nature of the disease has caused severe economic losses in the poultry industry worldwide. In this experiment ND virus (NDV was inactivated by two different chemicals binary ethylenimine (BEI and formaldehyde. Formaldehyde was used at 0.1%, while BEI was used at concentrations of 1 to 4 mM. NDV inactivation with BEI was done in various incubation temperatures and periods and the best result (30 °C, 4 mM BEI and 21 hrs treatment used as an experimental vaccine. Prepared inactivated NDV vaccines and a commercial vaccine were tested for their efficiency in generating humoral immune response in different groups of specific pathogen free (SPF chicks. Test groups received 0.2 ml formaldehyde inactivated NDV (NDVF, BEI inactivated NDV (NDVEI and Razi institute produced NDV vaccine (NDVR subcutaneously respectively. HI Log 2 total mean titer of NDVEI group (8.42 ± 0.12 were significantly higher than NDVF (7.64 ± 0.16 and NDVR (7.86 ± 0.11 groups (p<0.05. BEI-inactivated vaccine gave higher antibody titers than formaldehyde-inactivated vaccine and preserves both structural integrity and antigenicity of the virus. Thus, it might be possible to use these compounds as an inactivator agent for commercial NDV inactivated vaccines in future.
Zhu, Wenbo; Jin, Pengfei; Li, Jing-Xin; Zhu, Feng-Cai; Liu, Pei
Inactivated Enterovirus 71 (EV71) vaccines showed significant efficacy against the diseases associated with EV71 and a neutralizing antibody (NTAb) titer of 1:16-1:32 was suggested as the correlates of the vaccine protection. This paper aims to further estimate the immunological surrogate endpoints for the protection of inactivated EV71 vaccines and the effect factors. Pre-vaccination NTAb against EV71 at baseline (day 0), post-vaccination NTAb against EV71 at day 56, and the occurrence of laboratory-confirmed EV71-associated diseases during a 24-months follow-up period were collected from a phase 3 efficacy trial of an inactivated EV71 vaccine. We used the mixed-scaled logit model and the absolute sigmoid function by some extensions in continuous models to estimate the immunological surrogate endpoint for the EV71 vaccine protection, respectively. For children with a negative baseline of EV71 NTAb titers, an antibody level of 26.6 U/ml (1:30) was estimated to provide at least a 50% protection for 12 months, and an antibody level of 36.2 U/ml (1:42) may be needed to achieve a 50% protective level of the population for 24 months. Both the pre-vaccination NTAb level and the vaccine protective period could affect the estimation of the immunological surrogate for EV71 vaccine. A post-vaccination NTAb titer of 1:42 or more may be needed for long-term protection. NCT01508247.
Tano, Yoshio; Shimizu, Hiroyuki; Martin, Javier; Nishimura, Yorihiro; Simizu, Bunsiti; Miyamura, Tatsuo
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.
A randomized study to evaluate the immunogenicity and safety of a heptavalent diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis, haemophilus influenzae b, and meningococcal serogroup C combination vaccine administered to infants at 2, 4 and 12 months of age.
Thollot, Franck; Scheifele, David; Pankow-Culot, Heidemarie; Cheuvart, Brigitte; Leyssen, Maarten; Ulianov, Liliana; Miller, Jacqueline M
The immunogenicity and safety of the investigational diphtheria, tetanus, acellular pertussis, hepatitis B, poliomyelitis, Haemophilus influenzae type b (Hib) and meningococcal serogroup C (MenC) heptavalent combination vaccine were compared with those of licensed control vaccines. In this open, phase II, randomized study (NCT01090453), 480 infants from Germany, France and Canada received the heptavalent vaccine (Hepta group) or hexavalent and monovalent MenC control vaccines (HexaMenC group) co-administered with a 13-valent pneumococcal conjugate vaccine at 2, 4 and 12 months of age. Immunogenicity was measured 1 month after the second primary dose, and before and 1 month after the booster dose. Safety and reactogenicity were also evaluated. Non-inferiority of immune responses to MenC and Hib induced by 2-dose primary vaccination with the heptavalent vaccine versus control vaccines was demonstrated. In exploratory analyses, postprimary and postbooster functional antibody geometric mean titers against MenC tended to be lower (1119.5 vs. 3200.5; 2653.8 vs. 6028.4) and antibody geometric mean concentrations against Hib higher (1.594 vs. 0.671 μg/mL; 17.678 vs. 13.737 μg/mL) in the Hepta versus the HexaMenC group. The heptavalent and control vaccines were immunogenic to all other antigens, although immune responses to poliovirus were lower than expected in both groups. No differences in safety and reactogenicity profiles were detected between groups. The heptavalent vaccine induced non-inferior MenC and Hib responses compared with control vaccines. Both vaccination regimens, when administered at 2, 4 and 12 months of age, had comparable safety profiles and were immunogenic to all antigens, with lower-than-expected responses to poliomyelitis.
Martelli, P; Saleri, R; Cavalli, V; De Angelis, E; Ferrari, L; Benetti, M; Ferrarini, G; Merialdi, G; Borghetti, P
The systemic and respiratory local immune response induced by the intradermal administration of a commercial inactivated Mycoplasma hyopneumoniae whole-cell vaccine (Porcilis(®) MHYO ID ONCE - MSD AH) in comparison with two commercial vaccines administered via the intramuscular route and a negative control (adjuvant only) was investigated. Forty conventional M. hyopneumoniae-free pigs were randomly assigned to four groups (ten animals each): Group A=intradermal administration of the test vaccine by using the needle-less IDAL(®) vaccinator at a dose of 0.2 ml; Group B=intramuscular administration of a commercially available vaccine (vaccine B); Group C=intramuscular administration of the adjuvant only (2 ml of X-solve adjuvant); Group D=intramuscular administration of a commercially available vaccine (vaccine D). Pigs were vaccinated at 28 days of age. Blood and bronchoalveolar lavage (BAL) fluid samples were collected at vaccination (blood only), 4 and 8 weeks post-vaccination. Serum and BAL fluid were tested for the presence of antibodies by ELISA test. Peripheral blood monomorphonuclear cells (PBMC) were isolated to quantify the number of IFN-γ secreting cells by ELISpot. Moreover, cytokine gene expression from the BAL fluid was performed. Total antibodies against M. hyopneumoniae and specific IgG were detected in serum of intradermally and intramuscularly (vaccine B only) vaccinated pigs at 4 and 8 weeks post-vaccination. M. hyopneumoniae specific IgA were detected in BAL fluid from vaccinated animals (Groups A and B) but not from controls and animals vaccinated with the bacterin D (padministration of an adjuvanted bacterin induces both systemic and mucosal immune responses. Moreover, the intramuscularly administered commercial vaccines each had a different ability to stimulate the immune response both systemically and locally. Copyright © 2013 Elsevier B.V. All rights reserved.
Dunham, Stephen P; Bruce, Jennifer; Klein, Dieter; Flynn, J Norman; Golder, Matthew C; MacDonald, Susan; Jarrett, Oswald; Neil, James C
Protection against feline immunodeficiency virus (FIV) has been achieved using a variety of vaccines notably whole inactivated virus (WIV) and DNA. However protection against more virulent isolates, typical of those encountered in natural infections, has been difficult to achieve. In an attempt to improve protection against virulent FIV(GL8), we combined both DNA and WIV vaccines in a "prime-boost" approach. Thirty cats were divided into four groups receiving vaccinations and one unvaccinated control group. Following viral challenge, two vaccinated animals, one receiving DNA alone and one the prime-boost vaccine remained free of viraemia, whilst all controls became viraemic. Animals vaccinated with WIV showed apparent early enhancement of infection at 2 weeks post challenge (pc) with higher plasma viral RNA loads than control animals or cats immunised with DNA alone. Despite this, animals vaccinated with WIV or DNA alone showed significantly lower proviral loads in peripheral blood mononuclear cells and mesenteric lymph node cells, whilst those receiving the DNA-WIV prime-boost vaccine showed significantly lower proviral loads in PBMC, than control animals, at 35 weeks pc. Therefore both DNA and WIV vaccines conferred limited protection against viral challenge but the combination of WIV and DNA in a prime-boost approach appeared to offer no significant advantage over either vaccine alone.
Chu, Leonard Y; Ye, Ling; Dong, Ke; Compans, Richard W; Yang, Chinglai; Prausnitz, Mark R
This study tested the hypothesis that encapsulation of influenza vaccine in microneedle patches increases vaccine stability during storage at elevated temperature. Whole inactivated influenza virus vaccine (A/Puerto Rico/8/34) was formulated into dissolving microneedle patches and vaccine stability was evaluated by in vitro and in vivo assays of antigenicity and immunogenicity after storage for up to 3 months at 4, 25, 37 and 45°C. While liquid vaccine completely lost potency as determined by hemagglutination (HA) activity within 1-2 weeks outside of refrigeration, vaccine in microneedle patches lost 40-50% HA activity during or shortly after fabrication, but then had no significant additional loss of activity over 3 months of storage, independent of temperature. This level of stability required reduced humidity by packaging with desiccant, but was not affected by presence of oxygen. This finding was consistent with additional stability assays, including antigenicity of the vaccine measured by ELISA, virus particle morphological structure captured by transmission electron microscopy and protective immune responses by immunization of mice in vivo. These data show that inactivated influenza vaccine encapsulated in dissolving microneedle patches has enhanced stability during extended storage at elevated temperatures.
... Exclusive License: Purified Inactivated Dengue Tetravalent Vaccine Containing a Common 30 Nucleotide Deletion in the 3'-UTR of Dengue Types 1,2,3, and 4 AGENCY: National Institutes of Health, Public Health...., ``Development of Mutations Useful for Attenuating Dengue Viruses and Chimeric Dengue Viruses''-- European Patent...
Mucosal and systemic immunity were observed in broilers vaccinated with mannosylated chitosan adjuvated (MCA) inactivated A/Turkey/Virginia/158512/2002 (H7N2) and administered with and without recombinant Bacillus subtilis to elicit heterologous influenza strain protection. Previously, mucosal immu...
Habibi, Wazir Ahmad; Hirai, Takuya; Niazmand, Mohammad Hakim; Okumura, Naoko; Yamaguchi, Ryoji
We investigated the amyloidogenic potential of inactivated vaccines and the localized production of serum amyloid A (SAA) at the injection site in white layer chickens. Hens in the treated group were injected intramuscularly three times with high doses of inactivated oil-emulsion Salmonella Enteritidis vaccine and multivalent viral and bacterial inactivated oil-emulsion vaccines at two-week intervals. Chickens in the control group did not receive any inoculum. In the treated group, emaciation and granulomas were present, while several chickens died between 4 and 6 weeks after the first injection. Hepatomegaly was seen at necropsy, and the liver parenchyma showed inconsistent discolouration with patchy green to yellowish-brown areas, or sometimes red-brown areas with haemorrhage. Amyloid deposition in the liver, spleen, duodenum, and at injection sites was demonstrated using haematoxylin and eosin staining, Congo red, and immunohistochemistry. The incidence of chicken amyloid A (AA) amyloidosis was 47% (28 of 60) in the treated group. In addition, RT-PCR was used to identify chicken SAA mRNA expression in the liver and at the injection sites. Furthermore, SAA mRNA was detected by in situ hybridization in fibroblasts at the injection sites, and also in hepatocytes. We believe that this is the first report of the experimental induction of systemic AA amyloidosis in white layer chickens following repeated inoculation with inactivated vaccines without the administration of amyloid fibrils or other amyloid-enhancing factors.
Schiffelers, Marie-Jeanne W. A.; Blaauboer, Bas J.; Bakker, Wieger E.; Hendriksen, Coenraad F. M.
In April 2013 the mouse antibody serum neutralization test (SNT) was formally incorporated into European Pharmacopoeia monograph 0451 for potency testing of inactivated veterinary rabies vaccines. The SNT is designed to replace the highly variable and pain and distress causing NIH mouse rabies
The influenza H1N1 pandemic of 1918 was one of the worst medical disasters in human history. Recent studies have demonstrated that the hemagglutinin (HA) protein of the 1918 virus and 2009 H1N1 pandemic virus, the latter now a component of the seasonal trivalent inactivated influenza vaccine (TIV),...
Full Text Available In recent years, enterovirus D68 (EVD68 has been reported increasingly to be associated with severe respiratory tract infections and acute flaccid myelitis (AFM in children all over the world. Yet, no effective vaccines or antiviral drugs are currently available for EVD68. Although several experimental animal models have been developed, immunogenicity and protective efficacy of inactivated EVD68 vaccines has not been fully evaluated. To promote the development of vaccines, we established an Institute of Cancer Research (ICR suckling mouse model of EVD68 infection in this study. The results showed that ICR neonatal mice up to about nine days of age were susceptible to infection with EVD68 clinical strain US/MO/14-18947 by intraperitoneal injection. The infected mice exhibited progressive limb paralysis prior to death and the mortality of mice was age- and virus dose-dependent. Tissue viral load analysis showed that limb muscle and spinal cord were the major sites of viral replication. Moreover, histopathologic examination revealed the severe necrosis of the limb and juxtaspinal muscles, suggesting that US/MO/14-18947 has a strong tropism toward muscle tissues. Additionally, β-propiolactone-inactivated EVD68 vaccine showed high purity and quality and induced robust EVD68-specific neutralizing antibody responses in adult mice. Importantly, results from both antisera transfer and maternal immunization experiments clearly showed that inactivated EVD68 vaccine was able to protect against lethal viral infection in the mouse model. In short, these results demonstrate the successful establishment of the mouse model of EVD68 infection for evaluating candidate vaccines against EVD68 and also provide important information for the development of inactivated virus-based EVD68 vaccines.
Edens, Chris; Dybdahl-Sissoko, Naomi C; Weldon, William C; Oberste, M Steven; Prausnitz, Mark R
The phased replacement of oral polio vaccine (OPV) with inactivated polio vaccine (IPV) is expected to significantly complicate mass vaccination campaigns, which are an important component of the global polio eradication endgame strategy. To simplify mass vaccination with IPV, we developed microneedle patches that are easy to administer, have a small package size, generate no sharps waste and are inexpensive to manufacture. When administered to rhesus macaques, neutralizing antibody titers were equivalent among monkeys vaccinated using microneedle patches and conventional intramuscular injection for IPV types 1 and 2. Serologic response to IPV type 3 vaccination was weaker after microneedle patch vaccination compared to intramuscular injection; however, we suspect the administered type 3 dose was lower due to a flawed pre-production IPV type 3 analytical method. IPV vaccination using microneedle patches was well tolerated by the monkeys. We conclude that IPV vaccination using a microneedle patch is immunogenic in rhesus macaques and may offer a simpler method of IPV vaccination of people to facilitate polio eradication. Copyright © 2015 Elsevier Ltd. All rights reserved.
Jadi, R S; Sudeep, A B; Barde, P V; Arankalle, V A; Mishra, A C
A Vero cell based vaccine candidate against Chandipura (CHP) virus (Rhabdoviridae: Vesiculovirus), was developed and evaluated for immunogenicity in mice. Virus was purified by ultracentrifugation on 30% glycerol cushion followed by differential centrifugation on 10-60% sucrose gradient and inactivated with β-propio lactone at a concentration of 1:3500. The inactivated product was blended with aluminium phosphate (3%) and immunized 4-week-old Swiss albino mice. Neutralizing antibodies in the range of 1:10 to 160 and 1:80 to 1:320 was detected with 85% and 100% sero-conversion after 2nd and 3rd dose, respectively. All the immunized mice with antibody titer above 1:20 survived live virus challenge. The vaccine candidate has potential to be an efficient vaccine against CHP virus. Copyright © 2011 Elsevier Ltd. All rights reserved.
Yu, Wen-Zhou; Wen, Ning; Zhang, Yong; Wang, Hai-Bo; Fan, Chun-Xiang; Zhu, Shuang-Li; Xu, Wen-Bo; Liang, Xiao-Feng; Luo, Hui-Ming; Li, Li
Poliomyelitis has historically been endemic in China and has been considered an important cause of disability and death. We reviewed strategies and measures of poliomyelitis control and eradication from 1953 to 2012. Data from notifiable disease and routine immunization reporting systems and acute flaccid paralysis (AFP) surveillance were analyzed. About 20 000 poliomyelitis cases were reported annually in the prevaccine era. During 1965-1977, live, attenuated oral poliomyelitis vaccine (OPV) was administered to children through annual mass campaigns in the winter, and the number of poliomyelitis cases started to decline. A cold chain system was established during 1982, and OPV coverage increased during the early stage of the Expanded Programme on Immunization, from 1978 to 1988. Between 1989 and 1999, routine immunization was strengthened, supplementary immunization activities (SIAs) were conducted, and the AFP surveillance system was established. China reported a last indigenous poliomyelitis case in 1994 and was certified as free of polio in 2000. To maintain its polio-free status, China kept >90% coverage of 3 doses of OPV, conducted SIAs in high-risk areas, and maintained high-quality of AFP surveillance. China succeeded in stopping the outbreak in Xinjiang in 2011. China's polio-free status was achieved and maintained through strengthening routine immunization and implementing SIAs and AFP surveillance. © 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: email@example.com.
Full Text Available Enterovirus 71 (EV71, a major causative agent of hand-foot-and-mouth disease (HFMD, causes outbreaks among children in the Asia-Pacific region. A vaccine is urgently needed. Based on successful pre-clinical work, phase I and II clinical trials of an inactivated EV71 vaccine, which included the participants of 288 and 660 respectively, have been conducted. In the present study, the immune response and the correlated modulation of gene expression in the peripheral blood mononuclear cells (PBMCs of 30 infants (6 to 11 months immunized with this vaccine or placebo and consented to join this study in the phase II clinical trial were analyzed. The results showed significantly greater neutralizing antibody and specific T cell responses in vaccine group after two inoculations on days 0 and 28. Additionally, more than 600 functional genes that were up- or down-regulated in PBMCs were identified by the microarray assay, and these genes included 68 genes associated with the immune response in vaccine group. These results emphasize the gene expression profile of the immune system in response to an inactivated EV71 vaccine in humans and confirmed that such an immune response was generated as the result of the positive mobilization of the immune system. Furthermore, the immune response was not accompanied by the development of a remarkable inflammatory response.NCT01391494 and NCT01512706.
Ma, Xia; Guo, Zhenhuan; Shen, Zhiqiang; Wang, Jinliang; Hu, Yuanliang; Wang, Deyun
Two experiments were carried out. In immune response test, the immune enhancement of propolis, oilemulsion and aluminium salt were compared in guinea pig vaccinated with inactivated porcine parvovirus (PPV) vaccine. The result showed that three adjuvants could enhance antibody titer, T lymphocyte proliferation, IL-2 and IL-4 secretion of splenic lymphocyte. The action of propolis was similar to that of oilemulsion and superior to that of aluminium salt, especially in early period of vaccination propolis could accelerate antibody production. In immune protection test, the effects of three adjuvants on PPV infection were compared in guinea pig vaccinated with PPV vaccine then challenged with PPV. The result showed that propolis and oilemulsion could enhance the antibody titer, IL-2 and IL-4 content in serum and decrease the PPV content in blood and viscera. In the effect of improving cellular immune response, the propolis was the best. These results indicated that propolis possessed better immune enhancement and would be exploited into a effective adjuvant of inactivated vaccine. Copyright © 2011 Elsevier Inc. All rights reserved.
Kapczynski, Darrell R; Perkins, Laura L; Sellers, Holly S
Studies were performed to determine if mucosal vaccination with inactivated avian metapneumovirus (aMPV) subtype C protected turkey poults from clinical disease and virus replication following mucosal challenge. Decreases in clinical disease were not observed in vaccinated groups, and the vaccine failed to inhibit virus replication in the tracheas of 96% of vaccinated birds. Histopathologically, enhancement of pulmonary lesions following virus challenge was associated with birds receiving the inactivated aMPV vaccine compared to unvaccinated birds. As determined by an enzyme-linked immunosorbent assay (ELISA), all virus-challenged groups increased serum immunoglobulin (Ig) G and IgA antibody production against the virus following challenge; however, the unvaccinated aMPV-challenged group displayed the highest increases in virus-neutralizing antibody. On the basis of these results it is concluded that intranasal vaccination with inactivated aMPV does not induce protective immunity, reduce virus shedding, or result in decreased histopathologic lesions.
Zhang, Xiaoshu; An, Jing; Tu, Aixia; Liang, Xuefeng; Cui, Fuqiang; Zheng, Hui; Tang, Yu; Liu, Jianfeng; Wang, Xuxia; Zhang, Ningjing; Li, Hui
ABSTRACT Objective: Compare immune persistence from one dose of each of 3 different hepatitis A vaccines when given to school-age children: a domestic, live attenuated hepatitis A vaccine (H2 vaccine); a domestic inactivated hepatitis A vaccine (Healive®); and an imported, inactivated hepatitis A vaccine (Havrix®),.Methods: School-age children were randomized into 1 of 4 groups to receive a single dose of a vaccine: H2 vaccine, Healive®, Havrix®, or hepatitis B vaccine [control]. Serum samples were collected 12 and 24 months after vaccination for measurement of anti-HAV IgG using microparticle enzyme immunoassay. Seropositivity was defined as ≥ 20 mUI/ml. We compared groups on seropositivity and geometric mean concentration (GMC). Results: Seropositive rates for the H2, Healive®, Havrix®, and control groups were 64%, 94.4%, 73%, and 1.0%, respectively, 12-months post-vaccination; and 63%, 95.6%, 72%, and 1.0%, respectively 24-months post-vaccination. Seropositivity was greater for Healive® than for H2 and Havrix® at 12 months (p-values a single dose of inactivated hepatitis A vaccine and live attenuated hepatitis A vaccine. PMID:27494260
Apr 9, 2018 ... However, small ruminants are also susceptible to many diseases. ... while CCPP is a severe respiratory disease caused by Mycoplasma capricolum subsp. ... the cost of vaccination, resulting in healthier goats and reduced mortality. ... capital, solve two disparate problems: environmental pollution from unc.
Domingues, Carla Magda Allan S; de Fátima Pereira, Sirlene; Cunha Marreiros, Ana Carolina; Menezes, Nair; Flannery, Brendan
In August 2012, the Brazilian Ministry of Health introduced inactivated polio vaccine (IPV) as part of sequential polio vaccination schedule for all infants beginning their primary vaccination series. The revised childhood immunization schedule included 2 doses of IPV at 2 and 4 months of age followed by 2 doses of oral polio vaccine (OPV) at 6 and 15 months of age. One annual national polio immunization day was maintained to provide OPV to all children aged 6 to 59 months. The decision to introduce IPV was based on preventing rare cases of vaccine-associated paralytic polio, financially sustaining IPV introduction, ensuring equitable access to IPV, and preparing for future OPV cessation following global eradication. Introducing IPV during a national multivaccination campaign led to rapid uptake, despite challenges with local vaccine supply due to high wastage rates. Continuous monitoring is required to achieve high coverage with the sequential polio vaccine schedule. Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.
Povey, R. C.; Carman, P. S.; Ewert, E.
Dogs were successfully isolated for a period of either 52 or 64 weeks following vaccination with an inactivated, adjuvanted canine parvovirus-2 vaccine. Antibody persisted in all ten vaccinated dogs, although in one case by 52 weeks postvaccination only virus neutralizing antibody, and not hemagglutination-inhibiting antibody, could be detected. Sentinel unvaccinated dogs housed alongside the vaccinated dogs throughout the study remained free of canine parvovirus-2 antibody until challenged. ...
Muhammad Akram Muneer, Haji Ahmad Hashmi, Masood Rabbani, Zahid Munir Chaudhry and Ali M. Bahrami
Full Text Available A total of 160 one-day-old broiler chicks were used to evaluate the immunomodulatory effects of an inactivated Eimeria tenella vaccine and a live polyvalent imported antiococcidial vaccine (Coccivac. This study indicated that both of these vaccines did not adversely affect the development of serum antibody against Newcastle disease virus (NDV and the chicks vaccinated with either of the anticoccidial vaccines resisted the virulent NDV challenge. A study of the lymphoid organs such as bursa of fabricuis: thymus and spleen from the experimental chicks indicated that those organs were comparable with those from the chicks not vaccinated with these coccidial vaccines. The overall findings of this study indicate that anticoccidial vaccines do not have any effects on the immune functions of the vaccinates. In fact these vaccines prevented the occurrence of clinical coccidiosis in the vaccinates.
Kelly, H; Carcione, D; Dowse, G; Effler, P
Australian and New Zealand health authorities identified seasonal trivalent inactivated influenza vaccines manufactured by CSL Biotherapies as the probable cause of increased febrile convulsions in children under five within 24 hours of vaccination and recommended against their use in this age group. We quantified the benefit-risk profile of the CSL vaccines using the number needed to vaccinate and suggest they might have caused two to three hospital admissions due to febrile convulsions for every hospital admission due to influenza prevented.
Cyril Jean-Marie Martel
Full Text Available Trivalent inactivated vaccines (TIV against influenza are given to 350 million people every year. Most of these are non-adjuvanted vaccines whose immunogenicity and protective efficacy are considered suboptimal. Commercially available non-adjuvanted TIV are known to elicit mainly a humoral immune response, whereas the induction of cell-mediated immune responses is negligible. Recently, a cationic liposomal adjuvant (dimethyldioctadecylammonium/trehalose 6,6'-dibehenate, CAF01 was developed. CAF01 has proven to enhance both humoral and cell-mediated immune responses to a number of different experimental vaccine candidates. In this study, we compared the immune responses in ferrets to a commercially available TIV with the responses to the same vaccine mixed with the CAF01 adjuvant. Two recently circulating H1N1 viruses were used as challenge to test the vaccine efficacy. CAF01 improved the immunogenicity of the vaccine, with increased influenza-specific IgA and IgG levels. Additionally, CAF01 promoted cellular-mediated immunity as indicated by interferon-gamma expressing lymphocytes, measured by flow cytometry. CAF01 also enhanced the protection conferred by the vaccine by reducing the viral load measured in nasal washes by RT-PCR. Finally, CAF01 allowed for dose-reduction and led to higher levels of protection compared to TIV adjuvanted with a squalene emulsion. The data obtained in this human-relevant challenge model supports the potential of CAF01 in future influenza vaccines.
Robert B Couch
Full Text Available BACKGROUND: Concern for a pandemic caused by a newly emerged avian influenza A virus has led to clinical trials with candidate vaccines as preparation for such an event. Most trials have involved vaccines for influenza A (H5N1, A (H7N7 or A (H9N2. OBJECTIVE: To evaluate dosage-related safety and immunogenicity of an inactivated influenza A (H7N7 vaccine in humans. DESIGN: One hundred twenty-five healthy young adults were randomized to receive two doses intramuscularly of placebo or 7.5, 15, 45 or 90 µg of HA of an inactivated subunit influenza A (H7N7 vaccine (25 per group, four weeks apart. Reactogenicity was evaluated closely for one week and for any adverse effect for six months after each dose. Serum hemagglutination-inhibiting and neutralizing antibody responses were determined four weeks after each dose and at six months. RESULTS: Reactogenicity evaluations indicated the vaccinations were well tolerated. Only one subject developed a ≥4-fold serum hemagglutination-inhibition (HAI antibody response and a final titer of ≥1:40 four weeks after dose two and only five subjects developed a neutralizing antibody rise and a final titer of ≥1:40 in tests performed at a central laboratory. Four of the five were given the 45 or 90 µg HA dosage. A more sensitive HAI assay at the study site revealed a dose-response with increasing HA dosage but only 36% in the 90 µg HA group developed a ≥4-fold rise in antibody in this test and only one of these achieved a titer of ≥1:32. CONCLUSION: This inactivated subunit influenza A (H7N7 vaccine was safe but poorly immunogenic in humans. TRIALS REGISTRATION: ClinicalTrials.gov NCT00546585.
T. S. Saraswathy Subramaniam
Full Text Available Since 1992, surveillance for acute flaccid paralysis (AFP cases was introduced in Malaysia along with the establishment of the National Poliovirus Laboratory at the Institute for Medical Research. In 2008, the Ministry of Health, Malaysia, approved a vaccine policy change from oral polio vaccine to inactivated polio vaccine (IPV. Eight states started using IPV in the Expanded Immunization Programme, followed by the remaining states in January 2010. The objective of this study was to determine the viral aetiology of AFP cases below 15 years of age, before and after vaccine policy change from oral polio vaccine to inactivated polio vaccine. One hundred and seventy-nine enteroviruses were isolated from the 3394 stool specimens investigated between 1992 and December 2012. Fifty-six out of 107 virus isolates were polioviruses and the remaining were non-polio enteroviruses. Since 2009 after the sequential introduction of IPV in the childhood immunization programme, no Sabin polioviruses were isolated from AFP cases. In 2012, the laboratory AFP surveillance was supplemented with environmental surveillance with sewage sampling. Thirteen Sabin polioviruses were also isolated from sewage in the same year, but no vaccine-derived poliovirus was detected during this period.
Full Text Available Enveloped virus vaccines can be damaged by high osmotic strength solutions, such as those used to protect the vaccine antigen during drying, which contain high concentrations of sugars. We therefore studied shrinkage and activity loss of whole inactivated influenza virus in hyperosmotic solutions and used those findings to improve vaccine coating of microneedle patches for influenza vaccination. Using stopped-flow light scattering analysis, we found that the virus underwent an initial shrinkage on the order of 10% by volume within 5 s upon exposure to a hyperosmotic stress difference of 217 milliosmolarity. During this shrinkage, the virus envelope had very low osmotic water permeability (1 - 6×10-4 cm s-1 and high Arrhenius activation energy (Ea = 15.0 kcal mol-1, indicating that the water molecules diffused through the viral lipid membranes. After a quasi-stable state of approximately 20 s to 2 min, depending on the species and hypertonic osmotic strength difference of disaccharides, there was a second phase of viral shrinkage. At the highest osmotic strengths, this led to an undulating light scattering profile that appeared to be related to perturbation of the viral envelope resulting in loss of virus activity, as determined by in vitro hemagglutination measurements and in vivo immunogenicity studies in mice. Addition of carboxymethyl cellulose effectively prevented vaccine activity loss in vitro and in vivo, believed to be due to increasing the viscosity of concentrated sugar solution and thereby reducing osmotic stress during coating of microneedles. These results suggest that hyperosmotic solutions can cause biphasic shrinkage of whole inactivated influenza virus which can damage vaccine activity at high osmotic strength and that addition of a viscosity enhancer to the vaccine coating solution can prevent osmotically driven damage and thereby enable preparation of stable microneedle coating formulations for vaccination.
Mee, Edward T; Minor, Philip D; Martin, Javier
Definitive identification of poliovirus strains in vaccines is essential for quality control, particularly where multiple wild-type and Sabin strains are produced in the same facility. Sequence-based identification provides the ultimate in identity testing and would offer several advantages over serological methods. We employed random RT-PCR and high throughput sequencing to recover full-length genome sequences from monovalent and trivalent poliovirus vaccine products at various stages of the manufacturing process. All expected strains were detected in previously characterised products and the method permitted identification of strains comprising as little as 0.1% of sequence reads. Highly similar Mahoney and Sabin 1 strains were readily discriminated on the basis of specific variant positions. Analysis of a product known to contain incorrect strains demonstrated that the method correctly identified the contaminants. Random RT-PCR and shotgun sequencing provided high resolution identification of vaccine components. In addition to the recovery of full-length genome sequences, the method could also be easily adapted to the characterisation of minor variant frequencies and distinction of closely related products on the basis of distinguishing consensus and low frequency polymorphisms. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.
Chen, D; Periwal, S B; Larrivee, K; Zuleger, C; Erickson, C A; Endres, R L; Payne, L G
Both circulating and mucosal antibodies are considered important for protection against infection by influenza virus in humans and animals. However, current inactivated vaccines administered by intramuscular injection using a syringe and needle elicit primarily circulating antibodies. In this study, we report that epidermal powder immunization (EPI) via a unique powder delivery system elicits both serum and mucosal antibodies to an inactivated influenza virus vaccine. Serum antibody responses to influenza vaccine following EPI were enhanced by codelivery of cholera toxin (CT), a synthetic oligodeoxynucleotide containing immunostimulatory CpG motifs (CpG DNA), or the combination of these two adjuvants. In addition, secretory immunoglobulin A (sIgA) antibodies were detected in the saliva and mucosal lavages of the small intestine, trachea, and vaginal tract, although the titers were much lower than the IgG titers. The local origin of the sIgA antibodies was further shown by measuring antibodies released from cultured tracheal and small intestinal fragments and by detecting antigen-specific IgA-secreting cells in the lamina propria using ELISPOT assays. EPI with a single dose of influenza vaccine containing CT or CT and CpG DNA conferred complete protection against lethal challenges with an influenza virus isolated 30 years ago, whereas a prime and boost immunizations were required for protection in the absence of an adjuvant. The ability to elicit augmented circulating antibody and mucosal antibody responses makes EPI a promising alternative to needle injection for administering vaccines against influenza and other diseases.
Resik, Sonia; Tejeda, Alina; Fonseca, Magile; Sein, Carolyn; Hung, Lai Heng; Martinez, Yenisleidys; Diaz, Manuel; Okayasu, Hiromasa; Sutter, Roland W.
Introduction: We conducted a follow-on study to a phase I randomized, controlled trial conducted in Cuba, 2012, to assess the persistence of poliovirus antibodies at 21–22 months following booster dose of Sabin-IPV compared to Salk-IPV in adults who had received multiple doses of oral poliovirus vaccine (OPV) during childhood. Methods: In 2012, 60 healthy adult males aged 19–23 were randomized to receive one booster dose, of either Sabin-inactivated poliovirus vaccine (Sabin-IPV), adjuvant...
Westdijk, Janny; Koedam, Patrick; Barro, Mario; Steil, Benjamin P; Collin, Nicolas; Vedvick, Thomas S; Bakker, Wilfried A M; van der Ley, Peter; Kersten, Gideon
Six different adjuvants, each in combination with inactivated polio vaccine (IPV) produced with attenuated Sabin strains (sIPV), were evaluated for their ability to enhance virus neutralizing antibody titres (VNTs) in the rat potency model. The increase of VNTs was on average 3-, 15-, 24-fold with adjuvants after one immunization (serotypes 1, 2, and 3, respectively). Also after a boost immunization the VNTs of adjuvanted sIPV were on average another 7-20-27 times higher than after two inoculations of sIPV without adjuvant. The results indicate that it is feasible to increase the potency of inactivated polio vaccines by using adjuvants. Copyright © 2013 Elsevier Ltd. All rights reserved.
Yousafzai, Mohammad Tahir; Saleem, Ali Faisal; Mach, Ondrej; Baig, Attaullah; Sutter, Roland W; Zaidi, Anita K M
Administration of intradermal fractional dose of inactivated poliovirus vaccine (fIPV) has proven to be safe and immunogenic; however, its intradermal application using needle and syringe is technically difficult and requires trained personnel. We assessed feasibility of conducting an intradermal fIPV campaign in polio high risk neighborhood of Karachi using Tropis needle-free injector. During the one-day fIPV campaign, we measured average "application time" to administer fIPV with Tropis, collected ergonomic information and measured vaccine wastage. Eleven vaccinator teams, after two-day training, immunized 582 children between 4 months and 5 years of age. Average "application time" ranged from 35-75 seconds; the "application time" decreased with the number of children vaccinated from 68 to 38 seconds between 1st and 30th child. 10/11 (91%) vaccinator teams found no ergonomic issues; 1/11 (9%) assessed that it was not easy to remove air bubbles when filling the device. There was 0% vaccine loss reported. No adverse events following immunizations were reported. We demonstrated that it is feasible, safe and efficient to use Tropis for the administration of fIPV in a campaign setting.
Angela I Bordin
Full Text Available Rhodococcus equi is an important pathogen of foals that causes severe pneumonia. To date, there is no licensed vaccine effective against R. equi pneumonia of foals. The objectives of our study were to develop an electron beam (eBeam inactivated vaccine against R. equi and evaluate its immunogenicity. A dose of eBeam irradiation that inactivated replication of R. equi while maintaining outer cell wall integrity was identified. Enteral administration of eBeam inactivated R. equi increased interferon-γ production by peripheral blood mononuclear cells in response to stimulation with virulent R. equi and generated naso-pharyngeal R. equi-specific IgA in newborn foals. Our results indicate that eBeam irradiated R. equi administered enterally produce cell-mediated and upper respiratory mucosal immune responses, in the face of passively transferred maternal antibodies, similar to those produced in response to enteral administration of live organisms (a strategy which previously has been documented to protect foals against intrabronchial infection with virulent R. equi. No evidence of adverse effects was noted among vaccinated foals.
Sedeh, Farahnaz Motamedi; Shafaee, Kamal; Fatolahi, Hadi; Arbabi, Kourosh; Khorasani, Akbar
FMD is one of the most economically damaging diseases that affect livestock animals. In this study FMD Virus type A87/IRN was multiplied on BHK21 cells. The virus was titrated by TCID50 method, it was 10 7.5 /ml. The FMD virus samples were inactivated by gamma ray from 60 Co source at -20 deg C. Safety test was done by IBRS2 monolayer cell culture method, also antigenicity of irradiated and un-irradiated virus samples were studied by Complement Fixation Test. The dose/survival curve for irradiated FMD Virus was drawn, the optimum dose range for inactivation of FMDV type A87/IRN and unaltered antigenicity was obtained 40-44 kGy. The inactivated virus samples by irradiation and ethyleneimine (EI) were formulated respectively as vaccine with Al(OH) 3 gel and other substances. The vaccines were inoculated to Guinea pigs and the results of Serum Neutralization Test for the normal vaccine and radio-vaccine showed protective titer after 8 months. The potency test of the inactivated vaccines was done, PD50 Value of the vaccines were calculated 7.06 and 5.6 for inactivated vaccine by EI and gamma irradiation respectively. (author)
Srivastava, A K; Putnak, J R; Lee, S H; Hong, S P; Moon, S B; Barvir, D A; Zhao, B; Olson, R A; Kim, S O; Yoo, W D; Towle, A C; Vaughn, D W; Innis, B L; Eckels, K H
A second generation, purified, inactivated vaccine (PIV) against Japanese encephalitis (JE) virus was produced and tested in mice where it was found to be highly immunogenic and protective. The JE-PIV was made from an attenuated strain of JE virus propagated in certified Vero cells, purified, and inactivated with formalin. Its manufacture followed current GMP guidelines for the production of biologicals. The manufacturing process was efficient in generating a high yield of virus, essentially free of contaminating host cell proteins and nucleic acids. The PIV was formulated with aluminum hydroxide and administered to mice by subcutaneous inoculation. Vaccinated animals developed high-titered JE virus neutralizing antibodies in a dose dependent fashion after two injections. The vaccine protected mice against morbidity and mortality after challenge with live, virulent, JE virus. Compared with the existing licensed mouse brain-derived vaccine, JE-Vax, the Vero cell-derived JE-PIV was more immunogenic and as effective as preventing encephalitis in mice. The JE-PIV is currently being tested for safety and immunogenicity in volunteers.
Lúcia Helena de Oliveira
Full Text Available At the present time, the only poliovirus-caused poliomyelitis cases reported in Brazil and other countries of the Americas are of vaccine etiology. It is important for epidemiological surveillance and immunization programs to evaluate the epidemiological profile of cases of vaccine-associated paralytic poliomyelitis (VAPP in order to establish criteria for case definition and vaccination strategies. To research VAPP in Brazil, 30 cases diagnosed and classified as such by the Ministry of Health between 1989 and 1995 were submitted to a descriptive study of clinical, laboratory, and epidemiological data. In addition, the risk of occurrence of VAPP was estimated in relation to determinants based on a cohort of 3 656 persons with acute flaccid paralysis. Among individuals who had received oral polio vaccine (OPV from 4 to 40 days before the onset of paralysis, we found a relative risk of 8.88 (95% CI: 4.37-18.03 for VAPP as compared with persons who had not been vaccinated during the same time interval. For individuals who developed VAPP in the period following national vaccination days, the estimated relative risk was 2.94 (95% CI: 1.44-6.00. For the first dose of OPV administered to the general population the estimated risk was 1 case of VAPP for every 2.39 million doses; for total doses of OPV the risk was 1 case in 13.03 million doses. A major share of VAPP cases were related to children affected by prodromes (fever and gastrointestinal signs and/or symptoms, isolation of vaccine poliovirus type 2, paralysis of the lower limbs, and a mean age of 1 year.En la actualidad, los únicos casos de poliomielitis por poliovirus descritos en Brasil y en otros países americanos son de etiología vacunal. Para la vigilancia epidemiológica y los programas de inmunización es importante investigar el perfil epidemiológico de los casos de poliomielitis paralítica asociada a la vacuna (PPAV con el fin de establecer criterios para la definición de los casos
Sun, Yuelian; Christensen, Jakob Christensen; Hviid, Anders
-acellular pertussis–inactivated poliovirus– Haemophilus influenzae type b (DTaP-IPV-Hib) vaccine since September 2002. Objective To estimate the risk of febrile seizures and epilepsy after DTaP-IPV-Hib vaccination given at 3, 5, and 12 months. Design, Setting, and Participants A population-based cohort study of 378...
J.L. Heeney (Jonathan); P. de Vries (Petra); R. Dubbes (Rob); W. Koornstra (Willem); H. Niphuis; P. ten Haaft (Peter); J. Boes (Jolande); M.E.M. Dings (Marlinda); B. Morein (Bror); A.D.M.E. Osterhaus (Albert)
textabstractThis study attempted to determine if SIV vaccines could protect against challenge with peripheral blood mononuclear cells (PBMCs) from an SIV infected rhesus monkey. Mature Macaca mulatta were vaccinated four times with formalin inactivated SIVmac32H administered in MDP adjuvant (n = 8)
Martel, Cyril Jean-Marie; Agger, Else Marie; Jensen, Trine Hammer
Objectives: To assess the effect of CAF01 adjuvant associated to a commercial trivalent inactivated influenza vaccine in the ferret model. Methods: Ferrets were vaccinated with a range of doses of Sanofi-Pasteur's Vaxigrip with or without the CAF01 adjuvant, and challenged with either one of two H...
Cai, Yicun; Ku, Zhiqiang; Liu, Qingwei; Leng, Qibin; Huang, Zhong
Enterovirus 71 (EV71) and coxsackievirus A16 (CA16) are the two major causative agents of hand, foot and mouth disease (HFMD), which is an infectious disease frequently occurring in children. A bivalent vaccine against both EV71 and CA16 is highly desirable. In the present study, we compare monovalent inactivated EV71, monovalent inactivated CA16, and a combination vaccine candidate comprising of both inactivated EV71 and CA16, for their immunogenicity and in vivo protective efficacy. The two monovalent vaccines were found to elicit serum antibodies that potently neutralized the homologous virus but had no or weak neutralization activity against the heterologous one; in contrast, the bivalent vaccine immunized sera efficiently neutralized both EV71 and CA16. More importantly, passive immunization with the bivalent vaccine protected mice against either EV71 or CA16 lethal infections, whereas the monovalent vaccines only prevented the homologous but not the heterologous challenges. Together, our results demonstrate that the experimental bivalent vaccine comprising of inactivated EV71 and CA16 induces a balanced protective immunity against both EV71 and CA16, and thus provide proof-of-concept for further development of multivalent vaccines for broad protection against HFMD. Copyright © 2014 Elsevier Ltd. All rights reserved.
Aaby, Peter; Jensen, Henrik; Samb, Badara
Females given high-titre measles vaccine (HTMV) have high mortality; diphtheria-tetanus-pertussis (DTP) vaccination might be associated with increased female mortality. We aimed to assess whether DTP or inactivated poliovirus (IPV) administered after HTMV was associated with increased female...
Eduardo Souza Teixeira-Rocha
Full Text Available OBJETIVO: Descrever a ocorrência de poliomielite associada ao vírus vacinal no Brasil de 1995 a 2001 e determinar o risco observado para esse evento adverso. MÉTODOS: Este estudo retrospectivo utilizou os dados das fichas de investigação de notificações de paralisias flácidas agudas do Ministério da Saúde do Brasil. Foram considerados como casos os indivíduos com diagnóstico de paralisia flácida aguda com isolamento de vírus vacinal nas amostras de fezes ou seqüela compatível com poliomielite até 60 dias após o início da deficiência motora. Também foram incluídos os indivíduos em qualquer faixa etária que mantiveram contato com indivíduos vacinados entre 4 e 40 dias antes do início da doença e que desenvolveram deficiência motora entre 4 e 85 dias após esse contato. O risco foi calculado como a razão entre o número de casos e as respectivas doses aplicadas por ano, conforme o Programa Nacional de Imunização. RESULTADOS: Foram registrados 10 casos de pólio associada ao vírus vacinal no período. A média de idade foi de 4,7 meses. Quatro casos foram associados à primeira dose; quatro à segunda; e dois casos foram atribuídos a contato. Os sorotipos vacinais isolados foram o tipo 1 (dois casos; 2 (um caso; e 3 (três casos. Mais de um sorotipo foi isolado em quatro casos. Houve determinação dos sorotipos nos 10 casos. O risco observado para a poliomielite associada ao vírus vacinal durante o período foi de 1:5,11 milhões de primeiras doses e de 1:10,67 milhões para o total de doses. CONCLUSÃO: A presença de casos paralíticos provocados pela mesma política vacinal que objetiva a erradicação constitui-se no principal dilema técnico e ético da fase pós-eliminação da poliomielite.OBJECTIVE: To describe the occurrence of vaccine-associated paralytic poliomyelitis (VAPP in Brazil between 1995 and 2001 and to determine the level of risk for this adverse event. METHODS: This retrospective study
Wang, Rui-ning; Wang, Ya-bin; Geng, Jing-wei; Guo, Dong-hui; Liu, Fang; Chen, Hong-ying; Zhang, Hong-ying; Cui, Bao-an; Wei, Zhan-yong
Inactivated porcine parvovirus (PPV) vaccines are available commercially and widely used in the breeding herds. However, inactivated PPV vaccines have deficiencies in induction of specific cellular immune response. Transfer factor (TF) is a material that obtained from the leukocytes, and is a novel immune-stimulatory reagent that as a modulator of the immune system. In this study, the immunogenicity of PPV oil emulsion vaccine and the immuno-regulatory activities of TF were investigated. The inactivated PPV oil emulsion vaccines with or without TF were inoculated into BALB/c mice by subcutaneous injection. Then humoral and cellular immune responses were evaluated by indirect enzyme-linked immunosorbent assays (ELISA), fluorescence-activated cell sorter analyses (FACS). The results showed that the PPV specific immune responses could be evoked in mice by inoculating with PPV oil emulsion vaccine alone or by co-inoculation with TF. The cellular immune response levels in the co-inoculation groups were higher than those groups receiving the PPV oil emulsion vaccine alone, with the phenomena of higher level of IFN-γ, a little IL-6 and a trace of IL-4 in serum, and a vigorous T-cell response. However, there was no significant difference in antibody titers between TF synergy inactivated vaccine and the inactivated vaccine group (P>0.05). In conclusion, these results suggest that TF possess better cellular immune-enhancing capability and would be exploited into an effective immune-adjuvant for inactivated vaccines. Copyright © 2012 Elsevier Ltd. All rights reserved.
Lelie, P. N.; Reesink, H. W.; Niessen, J.; Brotman, B.; Prince, A. M.
The safety of a plasma-derived hepatitis-B vaccine inactivated by two heating steps (90 sec at 103 degrees C followed by 10 hr pasteurization at 65 degrees C) was validated in chimpanzees; 10(3) chimpanzee-infectious doses (CID50) of hepatitis-B virus (HBV), subjected to the purification steps
Full Text Available Tuberculosis (TB remains a pandemic affecting billions of people worldwide, thus stressing the need for new vaccines. Defining the correlates of vaccine protection is essential to achieve this goal. In this study, we used the wild boar model for mycobacterial infection and TB to characterize the protective mechanisms elicited by a new heat inactivated Mycobacterium bovis vaccine (IV. Oral vaccination with the IV resulted in significantly lower culture and lesion scores, particularly in the thorax, suggesting that the IV might provide a novel vaccine for TB control with special impact on the prevention of pulmonary disease, which is one of the limitations of current vaccines. Oral vaccination with the IV induced an adaptive antibody response and activation of the innate immune response including the complement component C3 and inflammasome. Mycobacterial DNA/RNA was not involved in inflammasome activation but increased C3 production by a still unknown mechanism. The results also suggested a protective mechanism mediated by the activation of IFN-γ producing CD8+ T cells by MHC I antigen presenting dendritic cells (DCs in response to vaccination with the IV, without a clear role for Th1 CD4+ T cells. These results support a role for DCs in triggering the immune response to the IV through a mechanism similar to the phagocyte response to PAMPs with a central role for C3 in protection against mycobacterial infection. Higher C3 levels may allow increased opsonophagocytosis and effective bacterial clearance, while interfering with CR3-mediated opsonic and nonopsonic phagocytosis of mycobacteria, a process that could be enhanced by specific antibodies against mycobacterial proteins induced by vaccination with the IV. These results suggest that the IV acts through novel mechanisms to protect against TB in wild boar.
Loeb, Mark; Russell, Margaret L; Manning, Vanessa; Fonseca, Kevin; Earn, David J D; Horsman, Gregory; Chokani, Khami; Vooght, Mark; Babiuk, Lorne; Schwartz, Lisa; Neupane, Binod; Singh, Pardeep; Walter, Stephen D; Pullenayegum, Eleanor
Whether vaccinating children with intranasal live attenuated influenza vaccine (LAIV) is more effective than inactivated influenza vaccine (IIV) in providing both direct protection in vaccinated persons and herd protection in unvaccinated persons is uncertain. Hutterite colonies, where members live in close-knit, small rural communities in which influenza virus infection regularly occurs, offer an opportunity to address this question. To determine whether vaccinating children and adolescents with LAIV provides better community protection than IIV. A cluster randomized blinded trial conducted between October 2012 and May 2015 over 3 influenza seasons. (ClinicalTrials.gov: NCT01653015). 52 Hutterite colonies in Alberta and Saskatchewan, Canada. 1186 Canadian children and adolescents aged 36 months to 15 years who received the study vaccine and 3425 community members who did not. Children were randomly assigned according to community in a blinded manner to receive standard dosing of either trivalent LAIV or trivalent IIV. The primary outcome was reverse transcriptase polymerase chain reaction-confirmed influenza A or B virus in all participants (vaccinated children and persons who did not receive the study vaccine). Mean vaccine coverage among children in the LAIV group was 76.9% versus 72.3% in the IIV group. Influenza virus infection occurred at a rate of 5.3% (295 of 5560 person-years) in the LAIV group versus 5.2% (304 of 5810 person-years) in the IIV group. The hazard ratio comparing LAIV with IIV for influenza A or B virus was 1.03 (95% CI, 0.85 to 1.24). The study was conducted in Hutterite communities, which may limit generalizability. Immunizing children with LAIV does not provide better community protection against influenza than IIV. The Canadian Institutes for Health Research.
Full Text Available We collected 30 cases of vaccine associated paralytic poliomyelitis (VAPP from 4081 cases of acute flaccid palsies cases notified from 1989 to 1995 to the Brazilian Ministry of Health. There were 30 VAPP cases with 56% of children younger than 1 year old, 56.7% of female. 46% of cases were reported in the Northeast. Ten P2 vaccine virus, 8 P3 and 2 P1 and associations amongst them were isolated. The clinical pattern in 60 days was: monoplegia (16, paraplegia (6, tetraplegia (5, hemiplegia (2 and triplegia (1. There was no strong relationship between fever, before or after the prodrome period, or the use of intramuscular medication to morbidity. CONCLUSION: if the anti-poliomyelitis strategy adopted in Brazil has lead to the eradication of the poliomyelitis with wild virus infection, the existence of a minimum risk of vaccine-associated poliomyelitis is a matter of concern because there will be a permanent neurological deficit.Trinta casos de poliomielite associada à vacinação oral (Sabin foram estudados a partir de 4081 notificações de paralisias agudas e flácidas feitas ao Ministério da Saúde no período de 1989 a 1995, com o objetivo de avaliar a gravidade do quadro neurológico. Dezesseis pacientes tiveram monoplegia, 6 paraplegia, 5 tetraplegia, 2 hemiplegia e 1 triplegia. Foram 56% em menores de 1 ano, 56,7% no sexo feminino, 46% dos casos provenientes do nordeste. Em 10 pacientes foi isolado o vírus vacinal P2, em oito o P3 e dois o P1. Os demais tinham associações de mais de um tipo de vírus. Febre antes ou após o período prodrômico e o uso de medicação intramuscular não se relacionaram a maior morbidade. A política antipoliomielite adotada no Brasil levou à erradicação da poliomielite pelo vírus selvagem com um risco mínimo do ponto de vista epidemiológico, porém ainda com custos individuais não desprezíveis.
Westdijk, Janny; Brugmans, Debbie; Martin, Javier; van't Oever, Aart; Bakker, Wilfried A M; Levels, Lonneke; Kersten, Gideon
GMP-batches of Sabin-IPV were characterized for their antigenic and immunogenic properties. Antigenic fingerprints of Sabin-IPV reveal that the D-antigen unit is not a fixed amount of antigen but depends on antibody and assay type. Instead of the D-antigen unit we propose standardization of IPV based on a combination of protein amount for dose and D-antigenicity for quality of the vaccine. Although Sabin-IPV type 2 is less immunogenic than regular wild type IPV type 2, the immunogenicity (virus neutralizing titers) per microgram antigen for Sabin-IPV type 2 is in the same order as for wild type serotypes 1 and 3. The latter observations are in line with data from human trials. This suggests that a higher dose of Sabin-IPV type 2 to compensate for the lower rat immunogenicity may not be necessary. Copyright © 2011 Elsevier Ltd. All rights reserved.
Hwang, Hye Suk; Lee, Young-Tae; Kim, Ki-Hye; Ko, Eun-Ju; Lee, Youri; Kwon, Young-Man; Kang, Sang-Moo
Formalin inactivated respiratory syncytial virus (FI-RSV) vaccination caused vaccine-enhanced respiratory disease (ERD) upon exposure to RSV in children. Virus-like particles presenting RSV F fusion protein (F VLP) are known to increase T helper type-1 (Th1) immune responses and avoid ERD in animal models. We hypothesized that F VLP would prime immune responses preventing ERD upon subsequent exposure to ERD-prone FI-RSV. Here, we demonstrated that heterologous F VLP priming and FI-RSV boosting of mice prevented FI-RSV vaccine-enhanced lung inflammation and eosinophilia upon RSV challenge. F VLP priming redirected pulmonary T cells toward effector CD8 T cells producing Th1 cytokines and significantly suppressed pulmonary Th2 cytokines. This study suggests that RSV F VLP priming would modulate and shift immune responses to subsequent exposure to ERD-prone FI-RSV vaccine and RSV infection, suppressing Th2 immune-mediated pulmonary histopathology and eosinophilia. Copyright © 2017. Published by Elsevier Inc.
Full Text Available Adjuvants play an important role in vaccine formulations by increasing their immunogenicity. In this study, the phenolic compound-rich J fraction (JFR of a Brazilian green propolis methanolic extract stimulated cellular and humoral immune responses when co-administered with an inactivated vaccine against swine herpesvirus type 1 (SuHV-1. When compared to control vaccines that used aluminium hydroxide as an adjuvant, the use of 10 mg/dose of JFR significantly increased (p < 0.05 neutralizing antibody titres against SuHV-1, as well as the percentage of protected animals following SuHV-1 challenge (p < 0.01. Furthermore, addition of phenolic compounds potentiated the performance of the control vaccine, leading to increased cellular and humoral immune responses and enhanced protection of animals after SuHV-1 challenge (p < 0.05. Prenylated compounds such as Artepillin C that are found in large quantities in JFR are likely to be the substances that are responsible for the adjuvant activity.
Murugappan, Senthil; Frijlink, Henderik W; Petrovsky, Nikolai; Hinrichs, Wouter L J
Vaccination is the primary intervention to contain influenza virus spread during seasonal and pandemic outbreaks. Pulmonary vaccination is gaining increasing attention for its ability to induce both local mucosal and systemic immune responses without the need for invasive injections. However, pulmonary administration of whole inactivated influenza virus (WIV) vaccine induces a Th2 dominant systemic immune response while a more balanced Th1/Th2 vaccine response may be preferred and only induces modest nasal immunity. This study evaluated immunity elicited by pulmonary versus intramuscular (i.m.) delivery of WIV, and tested whether the immune response could be improved by co-administration of delta (δ)-inulin, a novel carbohydrate-based particulate adjuvant. After pulmonary administration both unadjuvanted and δ-inulin adjuvanted WIV induced a potent systemic immune response, inducing higher serum anti-influenza IgG titers and nasal IgA titers than i.m. administration. Moreover, the addition of δ-inulin induced a more balanced Th1/Th2 response and induced higher nasal IgA titers versus pulmonary WIV alone. Pulmonary WIV alone or with δ-inulin induced hemagglutination inhibition (HI) titers>40, titers which are considered protective against influenza virus. In conclusion, in this study we have shown that δ-inulin adjuvanted WIV induces a better immune response after pulmonary administration than vaccine alone. Copyright © 2014 Elsevier B.V. All rights reserved.
Cashman, Patrick; Moberley, Sarah; Dalton, Craig; Stephenson, Jody; Elvidge, Elissa; Butler, Michelle; Durrheim, David N
Vaxtracker is a web based survey for active post marketing surveillance of Adverse Events Following Immunisation. It is designed to efficiently monitor vaccine safety of new vaccines by early signal detection of serious adverse events. The Vaxtracker system automates contact with the parents or carers of immunised children by email and/or sms message to their smart phone. A hyperlink on the email and text messages links to a web based survey exploring adverse events following the immunisation. The Vaxtracker concept was developed during 2011 (n=21), and piloted during the 2012 (n=200) and 2013 (n=477) influenza seasons for children receiving inactivated influenza vaccine (IIV) in the Hunter New England Local Health District, New South Wales, Australia. Survey results were reviewed by surveillance staff to detect any safety signals and compare adverse event frequencies among the different influenza vaccines administered. In 2012, 57% (n=113) of the 200 participants responded to the online survey and 61% (290/477) in 2013. Vaxtracker appears to be an effective method for actively monitoring adverse events following influenza vaccination in children. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.
Osadebe, Lynda U; MacNeil, Adam; Elmousaad, Hashim; Davis, Lora; Idris, Jibrin M; Haladu, Suleiman A; Adeoye, Olorunsogo B; Nguku, Patrick; Aliu-Mamudu, Uneratu; Hassan, Elizabeth; Vertefeuille, John; Bloland, Peter
Kano State, Nigeria, introduced inactivated polio vaccine (IPV) into its routine immunization (RI) schedule in March 2015 and was the pilot site for an RI data module for the National Health Management Information System (NHMIS). We determined factors impacting IPV introduction and the value of the RI module on monitoring new vaccine introduction. Two assessment approaches were used: (1) analysis of IPV vaccinations reported in NHMIS, and (2) survey of 20 local government areas (LGAs) and 60 associated health facilities (HF). By April 2015, 66% of LGAs had at least 20% of HFs administering IPV, by June all LGAs had HFs administering IPV and by July, 91% of the HFs in Kano reported administering IPV. Among surveyed staff, most rated training and implementation as successful. Among HFs, 97% had updated RI reporting tools, although only 50% had updated microplans. Challenges among HFs included: IPV shortages (20%), hesitancy to administer 2 injectable vaccines (28%), lack of knowledge on multi-dose vial policy (30%) and age of IPV administration (8%). The introduction of IPV was largely successful in Kano and the RI module was effective in monitoring progress, although certain gaps were noted, which should be used to inform plans for future vaccine introductions. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.
Moor, Kathrin; Wotzka, Sandra Y.; Toska, Albulena; Diard, Médéric; Hapfelmeier, Siegfried; Slack, Emma
Our mucosal surfaces are the main sites of non-vector-borne pathogen entry, as well as the main interface with our commensal microbiota. We are still only beginning to understand how mucosal adaptive immunity interacts with commensal and pathogenic microbes to influence factors such as infectivity, phenotypic diversity, and within-host evolution. This is in part due to difficulties in generating specific mucosal adaptive immune responses without disrupting the mucosal microbial ecosystem itself. Here, we present a very simple tool to generate inactivated mucosal vaccines from a broad range of culturable bacteria. Oral gavage of 1010 peracetic acid-inactivated bacteria induces high-titer-specific intestinal IgA in the absence of any measurable inflammation or species invasion. As a proof of principle, we demonstrate that this technique is sufficient to provide fully protective immunity in the murine model of invasive non-typhoidal Salmonellosis, even in the face of severe innate immune deficiency. PMID:26904024
Pencheva, Daniela; Genova-Kalou, Petia; Bryaskova, Rayna
Experimental and laboratory tests were carried out in order to identify the advantages of “ghost” antigens obtained by treatment of the bacterial cell with silver nanoparticles in comparison to the inactivated antigens obtained by classical methods as heating or treatment with formalin. The Minimal Bactericidal Concentrations (MBC) of the hybrid material containing silver nanoparticles (PVA/AgNps), used for inactivation of the tested E. coli strains were determined and they were categorized as susceptible to the action of silver nanoparticles. The changes in the structure of the bacterial cells obtained after the treatment with the hybrid material containing silver nanoparticles or with formaldehyde, respectively, were established by TEM (Transmission electron microscopy) analysis. The advantages of the “ghost” vaccines are expressed in undamaged cell wall and better immunogenicity, thus resulting in faster formation of specific titer after immunization of experimental animals. Key words: E. coli O149, E. coli O157H7, “ghost” vaccine, silver nanoparticles, TEM
Wu, Jun-Yu; Liu, Yan; Chen, Jiang-Ting; Xia, Ming; Zhang, Xiao-Mei
In 2002, the first Chinese domestic preservative-free inactivated hepatitis A vaccine, Healive®, was introduced in China. It is highly immunogenic, and provides lasting protection in healthy individuals and generates protective levels of antibodies in other at-risk individuals. Over 10 years since its first licensure, postmarketing surveillance data have confirmed the outstanding safety profile of the vaccine. Comparative clinical trials indicated that Healive® induce equal or similar immunogenicity with other currently available inactivated hepatitis A vaccines and are interchangeable for the course of HAV immunization in Chinese children. The vaccine is effective in curbing outbreaks of hepatitis A due to rapid seroconversion and the long incubation period of the disease. Additional issues surrounding the use of the vaccine are also reviewed. PMID:23032165
Co-administration of live measles and yellow fever vaccines and inactivated pentavalent vaccines is associated with increased mortality compared with measles and yellow fever vaccines only. An observational study from Guinea-Bissau
Fisker, Ane Bærent; Ravn, Henrik Bylling; Rodrigues, Amabelia
is replacing DTP in many low-income countries and yellow fever vaccine (YF) has been introduced to be given together with MV. Pentavalent and YF vaccines were introduced in Guinea-Bissau in 2008. We investigated whether co-administration of pentavalent vaccine with MV and yellow fever vaccine has similar......Studies from low-income countries indicate that co-administration of inactivated diphtheria-tetanus-pertussis (DTP) vaccine and live attenuated measles vaccine (MV) is associated with increased mortality compared with receiving MV only. Pentavalent (DTP-H. Influenza type B-Hepatitis B) vaccine...
Brady, Rebecca C; Hu, Wilson; Houchin, Vonda G; Eder, Frank S; Jackson, Kenneth C; Hartel, Gunter F; Sawlwin, Daphne C; Albano, Frank R; Greenberg, Michael
A trivalent inactivated influenza vaccine (CSL's TIV, CSL Limited) was licensed under USA accelerated approval regulations for use in persons≥18 years. We performed a randomized, observer-blind study to assess the safety and immunogenicity of CSL's TIV versus an established US-licensed vaccine in a population≥6 months to vaccination history determined the dosing regimen (one or two vaccinations). Subjects received CSL's TIV (n=739) or the established vaccine (n=735) in the autumn of 2009. Serum hemagglutination-inhibition titers were determined pre-vaccination and 30 days after the last vaccination. No febrile seizures or other vaccine-related SAEs were reported. After the first vaccination for Cohorts A and B, respectively, the relative risks of fever were 2.73 and 2.32 times higher for CSL's TIV compared to the established vaccine. Irritability and loss of appetite (for Cohort A) and malaise (for Cohort B) were also significantly higher for CSL's TIV compared to the established vaccine. Post-vaccination geometric mean titers (GMTs) for CSL's TIV versus the established vaccine were 385.49 vs. 382.45 for H1N1; 669.13 vs. 705.61 for H3N2; and 100.65 vs. 93.72 for B. CSL's TIV demonstrated immunological non-inferiority to the established vaccine in all cohorts. Copyright © 2014 Elsevier Ltd. All rights reserved.
Malheiro, Luís; Pinto, Sofia Correia; Sarmento, Antonio; Santos, Lurdes
As we approach the third decade since the WHO started addressing the eradication of poliomyelitis and leprosy, a reflection of the previous campaigns efficacy and an evaluation of further elimination feasibility is important to adapt and intensify the next steps. We performed a critical review of the poliomyelitis and leprosy eradication campaigns to evaluate their technical and operational feasibilities. Vaccination and active case search are highly effective tools against poliomyelitis. If political stability and good vaccination coverage is achieved, poliomyelitis will be an easy target for eradication. Leprosy, on the other hand, faces many barriers towards elimination. The lack of a high efficacy vaccine, the long asymptomatic but infective period, the lack of screening tests and a poorly established elimination target, prevents this disease from being eliminated. In a world where resources and funding are limited, it is apparent that poliomyelitis is a more feasible target for elimination than leprosy.
Full Text Available There is some evidence that annual vaccination of trivalent inactivated influenza vaccine (TIV may lead to reduced vaccine immunogenicity but evidence is lacking on whether vaccine efficacy is affected by prior vaccination history. The efficacy of one dose of TIV in children 6-8 y of age against influenza B is uncertain. We examined whether immunogenicity and efficacy of influenza vaccination in school-age children varied by age and past vaccination history.We conducted a randomized controlled trial of 2009-10 TIV. Influenza vaccination history in the two preceding years was recorded. Immunogenicity was assessed by comparison of HI titers before and one month after receipt of TIV/placebo. Subjects were followed up for 11 months with symptom diaries, and respiratory specimens were collected during acute respiratory illnesses to permit confirmation of influenza virus infections. We found that previous vaccination was associated with reduced antibody responses to TIV against seasonal A(H1N1 and A(H3N2 particularly in children 9-17 y of age, but increased antibody responses to the same lineage of influenza B virus in children 6-8 y of age. Serological responses to the influenza A vaccine viruses were high regardless of vaccination history. One dose of TIV appeared to be efficacious against confirmed influenza B in children 6-8 y of age regardless of vaccination history.Prior vaccination was associated with lower antibody titer rises following vaccination against seasonal influenza A vaccine viruses, but higher responses to influenza B among individuals primed with viruses from the same lineage in preceding years. In a year in which influenza B virus predominated, no impact of prior vaccination history was observed on vaccine efficacy against influenza B. The strains that circulated in the year of study did not allow us to study the effect of prior vaccination on vaccine efficacy against influenza A.
Yvonne E Thomassen
Full Text Available Worldwide efforts to eradicate polio caused a tipping point in polio vaccination strategies. A switch from the oral polio vaccine, which can cause circulating and virulent vaccine derived polioviruses, to inactivated polio vaccines (IPV is scheduled. Moreover, a manufacturing process, using attenuated virus strains instead of wild-type polioviruses, is demanded to enhance worldwide production of IPV, especially in low- and middle income countries. Therefore, development of an IPV from attenuated (Sabin poliovirus strains (sIPV was pursued. Starting from the current IPV production process based on wild type Salk strains, adaptations, such as lower virus cultivation temperature, were implemented. sIPV was produced at industrial scale followed by formulation of both plain and aluminium adjuvanted sIPV. The final products met the quality criteria, were immunogenic in rats, showed no toxicity in rabbits and could be released for testing in the clinic. Concluding, sIPV was developed to manufacturing scale. The technology can be transferred worldwide to support post polio-eradication biosafety goals.
Esposito, Susanna; Giavoli, Claudia; Trombetta, Claudia; Bianchini, Sonia; Montinaro, Valentina; Spada, Anna; Montomoli, Emanuele; Principi, Nicola
Obesity may be a risk factor for increased hospitalization and deaths from infections due to respiratory pathogens. Additionally, obese patients appear to have impaired immunity after some vaccinations. To evaluate the immunogenicity, safety and tolerability of an inactivated trivalent influenza vaccine (TIV) in overweight and obese children, 28 overweight/obese pediatric patients and 23 healthy normal weight controls aged 3-14 years received a dose of TIV. Four weeks after vaccine administration, significantly higher seroprotection rates against the A/H1N1 strain were observed among overweight/obese children compared with normal weight controls (pvaccination, similar or slightly higher seroconversion and seroprotection rates against the A/H1N1 and A/H3N2 strains were detected in overweight/obese than in normal weight children, whereas significantly higher rates of seroconversion and seroprotection against the B strain were found in overweight/obese patients than in normal weight controls (pvaccine administration (pchildren, antibody response to TIV administration is similar or slightly higher than that evidenced in normal weight subjects of similar age and this situation persists for at least 4 months after vaccine administration in the presence of a favorable safety profile. Copyright © 2015 Elsevier Ltd. All rights reserved.
Resik, Sonia; Tejeda, Alina; Fonseca, Magile; Sein, Carolyn; Hung, Lai Heng; Martinez, Yenisleidys; Diaz, Manuel; Okayasu, Hiromasa; Sutter, Roland W
We conducted a follow-on study to a phase I randomized, controlled trial conducted in Cuba, 2012, to assess the persistence of poliovirus antibodies at 21-22 months following booster dose of Sabin-IPV compared to Salk-IPV in adults who had received multiple doses of oral poliovirus vaccine (OPV) during childhood. In 2012, 60 healthy adult males aged 19-23 were randomized to receive one booster dose, of either Sabin-inactivated poliovirus vaccine (Sabin-IPV), adjuvanted Sabin-IPV (aSabin-IPV), or conventional Salk-IPV. In the original study, blood was collected at days 0 (before) and 28 (after vaccination), respectively. In this study, an additional blood sample was collected 21-22 months after vaccination, and tested for neutralizing antibodies to Sabin poliovirus types 1, 2 and 3. We collected sera from 59/60 (98.3%) subjects; 59/59 (100%) remained seropositive to all poliovirus types, 21-22 months after vaccination. The decay curves were very similar among the study groups. Between day 28 and 21-22 months, there was a reduction of ⩾87.4% in median antibody levels for all poliovirus types in all study groups, with no significant differences between the study groups. The decay of poliovirus antibodies over a 21-22-month period was similar regardless of the type of booster vaccine used, suggesting the scientific data of Salk IPV long-term persistence and decay may be broadly applicable to Sabin IPV.
Pervaiz, Aslam; Mbaeyi, Chukwuma; Baig, Mirza Amir; Burman, Ashley; Ahmed, Jamal A; Akter, Sharifa; Jatoi, Fayaz A; Mahamud, Abdirahman; Asghar, Rana Jawad; Azam, Naila; Shah, Muhammad Nadeem; Laghari, Mumtaz Ali; Soomro, Kamaluddin; Wadood, Mufti Zubair; Ehrhardt, Derek; Safdar, Rana M; Farag, Noha
Following the declaration of eradication of wild poliovirus (WPV) type 2 in September 2015, trivalent oral poliovirus vaccine (tOPV) was withdrawn globally to reduce the risk for type 2 vaccine-derived poliovirus (VDPV2) transmission; all countries implemented a synchronized switch to bivalent OPV (type 1 and 3) in April 2016 (1,2). Any isolation of VDPV2 after the switch is to be treated as a potential public health emergency and might indicate the need for supplementary immunization activities (3,4). On August 9, 2016, VDPV2 was isolated from a sewage sample taken from an environmental surveillance site in Hyderabad, Sindh province, Pakistan. Possible vaccination activities in response to VDPV2 isolation include the use of injectable inactivated polio vaccine (IPV), which poses no risk for vaccine-derived poliovirus transmission. Fractional-dose, intradermal IPV (fIPV), one fifth of the standard intramuscular dose, has been developed to more efficiently manage limited IPV supplies. fIPV has been shown in some studies to be noninferior to full-dose IPV (5,6) and was used successfully in response to a similar detection of a single VDPV2 isolate from sewage in India (7). Injectable fIPV was used for response activities in Hyderabad and three neighboring districts. This report describes the findings of an assessment of preparatory activities and subsequent implementation of the fIPV campaign. Despite achieving high coverage (>80%), several operational challenges were noted. The lessons learned from this campaign could help to guide the planning and implementation of future fIPV vaccination activities.
Jin, Pengfei; Li, Jingxin; Zhang, Xuefeng; Meng, Fangyue; Zhou, Yang; Yao, Xuejun; Gan, Zhengkai; Zhu, Fengcai
A primary goal of this study was to establish the serological mechanistic correlate of protection (mCoP) for an inactivated Enterovirus 71 (EV71) vaccine. We used the Prentice criterion framework and scaled logit model to explore the relationship between the neutralizing antibody (NTAb) and EV71-associated disease, and to build a protection curve for estimating the efficacy of EV71 vaccine. Data of NTAb at day 56 post-vaccination and the occurrence of EV71-associated disease during a 12-month follow-up period were collected from a phase 3 efficacy trial of EV71 vaccine in this study. NTAb at day 56 post-vaccination in participants met the Prentice criterion framework. According to the protection curve, the antibody levels of 14.7, 27.8, 55.7, 129.0 and 459.4 (U/mL) were associated with 50%, 60%, 70%, 80% and 90% clinical protection rate, respectively. Vaccine efficacy predicted by the model was 81.5%, which was very similar to the actual vaccine efficacy of 80.4% (95% CI, 58.2, 90.8) observed in the phase 3 trial. NTAb titers post-vaccination can be validated as mCoP for evaluating the efficacy of an inactivated enterovirus 71 vaccine, with a titers of 14.7 (U/ml) as a surrogate associated with the protection of 50% against EV71-associated disease.
Gamoh, K; Senda, M; Inoue, Y; Itoh, O
Canine parvovirus type 2a (CPV-2a) and type 2b (CPV-2b) have recently been isolated from cats throughout the world, and CPV-2b strain FP84 has been reported to be virulent in domestic cats. Although live feline panleucopenia virus (FPLV) vaccines protect domestic cats from CPV infection, the efficacy of inactivated FPLV vaccines has not been established. In this study, two domestic cats were vaccinated with a commercial inactivated FPLV vaccine and challenged with CPV-2b strain FP84 isolated from a domestic cat. The cats were protected against CPV-2b strain FP84 infection and their clinical signs were suppressed, although the two unvaccinated cats showed the typical clinical signs of parvovirus infection.
Mao, Qunying; Wang, Yiping; Shao, Jie; Ying, Zhifang; Gao, Fan; Yao, Xin; Li, Changgui; Ye, Qiang; Xu, Miao; Li, Rongcheng; Zhu, Fengcai; Liang, Zhenglun
Enterovirus 71 (EV71) is the key pathogen for Hand, Foot, and Mouth Disease (HFMD) and can result in severe neurological complications and death among young children. Three inactivated-EV71 vaccines have gone through phase III clinical trials and have demonstrated good safety and efficacy. These vaccines will benefit young children under the threat of severe HFMD. However, the potential immunization-related compatibility for different enterovirus vaccines remains unclear, making it hard to include the EV71 vaccine in Expanded Program on Immunization (EPI). Here, we measured the neutralizing antibodies (NTAbs) against EV71, Coxsackievirus A16 (CA16) and Poliovirus from infants enrolled in those EV71 vaccine clinical trials. The results indicated that the levels of NTAb GMTs for EV71 increased significantly in all 3 vaccine groups (high, middle and low dosages, respectively) post-vaccination. Seroconversion ratios and Geometric mean fold increase were significantly higher in the vaccine groups (≥7/9 and 8.9～228.1) than in the placebo group (≤1/10 and 0.8～1.7, P Poliovirus. The decrease of 3 types of Poliovirus NTAb GMTs and an increase of CA16 GMTs post-EV71-vaccination were found in vaccine and placebo groups. Further animal study on CA16 and poliovirus vaccine co-immunization or pre-immunization with EV71 vaccine in mice indicated that there was no NTAb cross-activity between EV71 and CA16/Poliovirus. Our research showed that inactivated-EV71 vaccine has good specific-neutralizing capacity and can be included in EPI. PMID:25715318
Mao, Qunying; Wang, Yiping; Shao, Jie; Ying, Zhifang; Gao, Fan; Yao, Xin; Li, Changgui; Ye, Qiang; Xu, Miao; Li, Rongcheng; Zhu, Fengcai; Liang, Zhenglun
Enterovirus 71 (EV71) is the key pathogen for Hand, Foot, and Mouth Disease (HFMD) and can result in severe neurological complications and death among young children. Three inactivated-EV71 vaccines have gone through phase III clinical trials and have demonstrated good safety and efficacy. These vaccines will benefit young children under the threat of severe HFMD. However, the potential immunization-related compatibility for different enterovirus vaccines remains unclear, making it hard to include the EV71 vaccine in Expanded Program on Immunization (EPI). Here, we measured the neutralizing antibodies (NTAbs) against EV71, Coxsackievirus A16 (CA16) and Poliovirus from infants enrolled in those EV71 vaccine clinical trials. The results indicated that the levels of NTAb GMTs for EV71 increased significantly in all 3 vaccine groups (high, middle and low dosages, respectively) post-vaccination. Seroconversion ratios and Geometric mean fold increase were significantly higher in the vaccine groups (≥ 7/9 and 8.9 ～ 228.1) than in the placebo group (≤ 1/10 and 0.8 ～ 1.7, P < 0.05). But no similar NTAb response trends were found in CA16 and 3 types of Poliovirus. The decrease of 3 types of Poliovirus NTAb GMTs and an increase of CA16 GMTs post-EV71-vaccination were found in vaccine and placebo groups. Further animal study on CA16 and poliovirus vaccine co-immunization or pre-immunization with EV71 vaccine in mice indicated that there was no NTAb cross-activity between EV71 and CA16/Poliovirus. Our research showed that inactivated-EV71 vaccine has good specific-neutralizing capacity and can be included in EPI.
Kamal, Ram P; Blanchfield, Kristy; Belser, Jessica A; Music, Nedzad; Tzeng, Wen-Pin; Holiday, Crystal; Burroughs, Ashley; Sun, Xiangjie; Maines, Taronna R; Levine, Min Z; York, Ian A
Avian influenza viruses of the H7 hemagglutinin (HA) subtype present a significant public health threat, as evidenced by the ongoing outbreak of human A(H7N9) infections in China. When evaluated by hemagglutination inhibition (HI) and microneutralization (MN) assays, H7 viruses and vaccines are found to induce lower level of neutralizing antibodies (nAb) than do their seasonal counterparts, making it difficult to develop and evaluate prepandemic vaccines. We have previously shown that purified recombinant H7 HA appear to be poorly immunogenic in that they induce low levels of HI and MN antibodies. In this study, we immunized mice with whole inactivated reverse genetics reassortant (RG) viruses expressing HA and neuraminidase (NA) from 3 different H7 viruses [A/Shanghai/2/2013(H7N9), A/Netherlands/219/2003(H7N7), and A/New York/107/2003(H7N2)] or with human A(H1N1)pdm09 (A/California/07/2009-like) or A(H3N2) (A/Perth16/2009) viruses. Mice produced equivalent titers of antibodies to all viruses as measured by enzyme-linked immunosorbent assay (ELISA). However, the antibody titers induced by H7 viruses were significantly lower when measured by HI and MN assays. Despite inducing very low levels of nAb, H7 vaccines conferred complete protection against homologous virus challenge in mice, and the serum antibodies directed against the HA head region were capable of mediating protection. The apparently low immunogenicity associated with H7 viruses and vaccines may be at least partly related to measuring antibody titers with the traditional HI and MN assays, which may not provide a true measure of protective immunity associated with H7 immunization. This study underscores the need for development of additional correlates of protection for prepandemic vaccines. IMPORTANCE H7 avian influenza viruses present a serious risk to human health. Preparedness efforts include development of prepandemic vaccines. For seasonal influenza viruses, protection is correlated with antibody
Immunogenicity and safety evaluation of bivalent types 1 and 3 oral poliovirus vaccine by comparing different poliomyelitis vaccination schedules in China: A randomized controlled non-inferiority clinical trial.
Qiu, Jingjun; Yang, Yunkai; Huang, Lirong; Wang, Ling; Jiang, Zhiwei; Gong, Jian; Wang, Wei; Wang, Hongyan; Guo, Shaohong; Li, Chanjuan; Wei, Shuyuan; Mo, Zhaojun; Xia, Jielai
The type 2 component of the oral poliovirus vaccine is targeted for global withdrawal through a switch from the trivalent oral poliovirus vaccine (tOPV) to a bivalent oral poliovirus vaccine (bOPV). The switch is intended to prevent paralytic polio caused by circulating vaccine-derived poliovirus type 2. We aimed to assess the immunogenicity and safety profile of 6 vaccination schedules with different sequential doses of inactivated poliovirus vaccine (IPV), tOPV, or bOPV. A randomized controlled trial was conducted in China in 2015. Healthy newborn babies randomly received one of the following 6 vaccination schedules: cIPV-bOPV-bOPV(I-B-B), cIPV-tOPV-tOPV(I-T-T), cIPV-cIPV-bOPV(I-I-B), cIPV-cIPV-tOPV(I-I-T), cIPV-cIPV-cIPV(I-I-I), or tOPV-tOPV-tOPV(T-T-T). Doses were administered sequentially at 4-6 week intervals after collecting baseline blood samples. Patients were proactively followed up for observation of adverse events after the first dose and 30 days after all doses. The primary study objective was to investigate the immunogenicity and safety profile of different vaccine schedules, evaluated by seroconversion, seroprotection and antibody titer against poliovirus types 1, 2, and 3 in the per-protocol population. Of 600 newborn babies enrolled, 504 (84.0%) were included in the per-protocol population. For type 1 poliovirus, the differences in the seroconversion were 1.17% (95% CI = -2.74%, 5.08%) between I-B-B and I-T-T and 0.00% (95% CI: -6.99%, 6.99%) between I-I-B and I-I-T; for type 3 poliovirus, differences in the seroconversion were 3.49% (95% CI: -1.50%, 8.48%) between I-B-B and I-T-T and -2.32% (95% CI: -5.51%, 0.86%) between I-I-B and I-I-T. The non-inferiority conclusion was achieved in both poliovirus type 1 and 3 with the margin of -10%. Of 24 serious adverse events reported, no one was vaccine-related. The vaccination schedules with bOPV followed by one or 2 doses of IPV were recommended to substitute for vaccinations involving tOPV without
Zurbriggen, Sebastian; Tobler, Kurt; Abril, Carlos; Diedrich, Sabine; Ackermann, Mathias; Pallansch, Mark A; Metzler, Alfred
From 2001 to 2004, Switzerland switched from routine vaccination with oral polio vaccine (OPV) to inactivated polio vaccine (IPV), using both vaccines in the intervening period. Since IPV is less effective at inducing mucosal immunity than OPV, this change might allow imported poliovirus to circulate undetected more easily in an increasingly IPV-immunized population. Environmental monitoring is a recognized tool for identifying polioviruses in a community. To look for evidence of poliovirus circulation following cessation of OPV use, two sewage treatment plants located in the Zurich area were sampled from 2004 to 2006. Following virus isolation using either RD or L20B cells, enteroviruses and polioviruses were identified by reverse transcription-PCR. A total of 20 out of 174 wastewater samples were positive for 62 Sabin-like isolates. One isolate from each poliovirus-positive sample was analyzed in more detail. Sequencing the complete viral protein 1 (VP1) capsid coding region, as well as intratypic differentiation (ITD), identified 3 Sabin type 1, 13 Sabin type 2, and 4 Sabin type 3 strains. One serotype 1 strain showed a discordant result in the ITD. Three-quarters of the strains showed mutations within the 5' untranslated region and VP1, known to be associated with reversion to virulence. Moreover, three strains showed heterotypic recombination (S2/S1 and S3/S2/S3). The low number of synonymous mutations and the partial temperature sensitivity are not consistent with extended circulation of these Sabin virus strains. Nevertheless, the continuous introduction of polioviruses into the community emphasizes the necessity for uninterrupted child vaccination to maintain high herd immunity.
Full Text Available Combination of CVCVA5 adjuvant and commercial avian influenza (AI vaccine has been previously demonstrated to provide good protection against different AI viruses in chickens. In this study, we further investigated the protective immunity of CVCVA5-adjuvanted oil-emulsion inactivated AI vaccine in chickens, ducks and geese. Compared to the commercial H5 inactivated vaccine, the H5-CVCVA5 vaccine induced significantly higher titers of hemaglutinin inhibitory antibodies in three lines of broiler chickens and ducks, elongated the antibody persistence periods in geese, elevated the levels of cross serum neutralization antibody against different clade and subclade H5 AI viruses in chicken embryos. High levels of mucosal antibody were detected in chickens injected with the H5 or H9-CVCA5 vaccine. Furthermore, cellular immune response was markedly improved in terms of increasing the serum levels of cytokine interferon-γ and interleukine 4, promoting proliferation of splenocytes and upregulating cytotoxicity activity in both H5- and H9-CVCVA5 vaccinated chickens. Together, these results provide evidence that AI vaccines supplemented with CVCVA5 adjuvant is a promising approach for overcoming the limitation of vaccine strain specificity of protection.
Luiza Helena Falleiros Carvalho
Full Text Available OBJETIVOS: Apresentar uma atualização da situação da poliomielite no mundo, número de casos anuais, regiões mais atingidas pela doença, vacinas disponíveis na atualidade, seus riscos e benefícios, utilização da vacina monovalente, riscos da disseminação de um vírus mutante na comunidade, progressos que têm sido realizados em termos de erradicação mundial e as propostas da Organização Mundial da Saúde (OMS nesse período de transição entre a erradicação global e o período pós-erradicação. FONTE DE DADOS: Foram consultadas bases de dados no período de 1955 a 2005 em MEDLINE, LILACS, The Web, Doctor's Guide; site da OMS e Organização Pan-Americana da Saúde (OPAS e livro-texto. SÍNTESE DOS DADOS: Em 1988, a OMS estabeleceu como meta a erradicação da doença e a interrupção da transmissão do vírus selvagem globalmente. Desde então, houve um dramático impacto no declínio da doença, embora em 2005 ainda existam alguns países considerados endêmicos e outros onde a pólio retornou, por conta de vírus importados. As vacinas utilizadas no mundo são as clássicas tOPV e IPV e, dentro desse processo de erradicação, o uso de vacinas mOPV tem sido estimulado nos locais em que circula apenas um tipo de poliovírus. Entretanto, as vacinas OPV, além de disseminarem o vírus na comunidade, podem causar paralisias por reversão do processo de neurovirulência. CONCLUSÕES:Para um mundo livre da doença poliomielite, será preciso retirar o vírus de circulação, o que só será possível se a vacina OPV for descontinuada, conforme propostas da OMS para esse período de transição e para a era pós-erradicação.OBJECTIVES: To present an update on the status of poliomyelitis worldwide, number of cases per year, regions most affected by the disease, vaccines currently available, their risks and benefits, monovalent vaccine use, risks of disseminating a mutant virus in the community, progress that has been made in
Kittikraisak, Wanitchaya; Suntarattiwong, Piyarat; Ditsungnoen, Darunee; Pallas, Sarah E; Abimbola, Taiwo O; Klungthong, Chonticha; Fernandez, Stefan; Srisarang, Suchada; Chotpitayasunondh, Tawee; Dawood, Fatimah S; Olsen, Sonja J; Lindblade, Kim A
Vaccination is the best measure to prevent influenza. We conducted a cost-effectiveness evaluation of trivalent inactivated seasonal influenza vaccination, compared to no vaccination, in children ≤60 months of age participating in a prospective cohort study in Bangkok, Thailand. A static decision tree model was constructed to simulate the population of children in the cohort. Proportions of children with laboratory-confirmed influenza were derived from children followed weekly. The societal perspective and one-year analytic horizon were used for each influenza season; the model was repeated for three influenza seasons (2012-2014). Direct and indirect costs associated with influenza illness were collected and summed. Cost of the trivalent inactivated seasonal influenza vaccine (IIV3) including promotion, administration, and supervision cost was added for children who were vaccinated. Quality-adjusted life years (QALY), derived from literature, were used to quantify health outcomes. The incremental cost-effectiveness ratio (ICER) was calculated as the difference in the expected total costs between the vaccinated and unvaccinated groups divided by the difference in QALYs for both groups. Compared to no vaccination, IIV3 vaccination among children ≤60 months in our cohort was not cost-effective in the introductory year (2012 season; 24,450 USD/QALY gained), highly cost-effective in the 2013 season (554 USD/QALY gained), and cost-effective in the 2014 season (16,200 USD/QALY gained). The cost-effectiveness of IIV3 vaccination among children participating in the cohort study varied by influenza season, with vaccine cost and proportion of high-risk children demonstrating the greatest influence in sensitivity analyses. Vaccinating children against influenza can be economically favorable depending on the maturity of the program, influenza vaccine performance, and target population.
Full Text Available Vaccination is the best measure to prevent influenza. We conducted a cost-effectiveness evaluation of trivalent inactivated seasonal influenza vaccination, compared to no vaccination, in children ≤60 months of age participating in a prospective cohort study in Bangkok, Thailand.A static decision tree model was constructed to simulate the population of children in the cohort. Proportions of children with laboratory-confirmed influenza were derived from children followed weekly. The societal perspective and one-year analytic horizon were used for each influenza season; the model was repeated for three influenza seasons (2012-2014. Direct and indirect costs associated with influenza illness were collected and summed. Cost of the trivalent inactivated seasonal influenza vaccine (IIV3 including promotion, administration, and supervision cost was added for children who were vaccinated. Quality-adjusted life years (QALY, derived from literature, were used to quantify health outcomes. The incremental cost-effectiveness ratio (ICER was calculated as the difference in the expected total costs between the vaccinated and unvaccinated groups divided by the difference in QALYs for both groups.Compared to no vaccination, IIV3 vaccination among children ≤60 months in our cohort was not cost-effective in the introductory year (2012 season; 24,450 USD/QALY gained, highly cost-effective in the 2013 season (554 USD/QALY gained, and cost-effective in the 2014 season (16,200 USD/QALY gained.The cost-effectiveness of IIV3 vaccination among children participating in the cohort study varied by influenza season, with vaccine cost and proportion of high-risk children demonstrating the greatest influence in sensitivity analyses. Vaccinating children against influenza can be economically favorable depending on the maturity of the program, influenza vaccine performance, and target population.
Chandir, Subhash; Dharma, Vijay Kumar; Siddiqi, Danya Arif; Khan, Aamir Javed
Despite multiple rounds of immunization campaigns, it has not been possible to achieve optimum immunization coverage for poliovirus in Pakistan. Supplementary activities to improve coverage of immunization, such as door-to-door campaigns are constrained by several factors including inaccurate hand-drawn maps and a lack of means to objectively monitor field teams in real time, resulting in suboptimal vaccine coverage during campaigns. Global System for Mobile Communications (GSM) - based tracking of mobile subscriber identity modules (SIMs) of vaccinators provides a low-cost solution to identify missed areas and ensure effective immunization coverage. We conducted a pilot study to investigate the feasibility of using GSM technology to track vaccinators through observing indicators including acceptability, ease of implementation, costs and scalability as well as the likelihood of ownership by District Health Officials. The real-time location of the field teams was displayed on a GSM tracking web dashboard accessible by supervisors and managers for effective monitoring of workforce attendance including 'time in-time out', and discerning if all target areas - specifically remote and high-risk locations - had been reached. Direct access to this information by supervisors eliminated the possibility of data fudging and inaccurate reporting by workers regarding their mobility. The tracking cost per vaccinator was USD 0.26/month. Our study shows that GSM-based tracking is potentially a cost-efficient approach, results in better monitoring and accountability, is scalable and provides the potential for improved geographic coverage of health services. Copyright © 2017 Elsevier Ltd. All rights reserved.
Blankenhorn, Anne-Line; Cernuschi, Tania; Zaffran, Michel J
In May 2012, the World Health Assembly declared the completion of poliovirus eradication a programmatic emergency for global public health and called for a comprehensive polio endgame strategy. The Polio Eradication and Endgame Strategic Plan 2013-2018 was developed in response to this call and demands that all countries using Oral Polio Vaccine (OPV) only introduce at least 1 dose of Inactivated Polio Vaccine (IPV) into routine immunization schedules by the end of 2015. In November 2013, the Board of Gavi (the Vaccine Alliance) approved the provision of support for IPV introduction in the 72 Gavi-eligible countries. Following analytical work and stakeholder consultations, the IPV Immunization Systems Management Group (IMG) presented a proposal to provide exceptional financial support for IPV introduction to additional OPV-only using countries not eligible for Gavi support and that would otherwise not be able to mobilize the necessary financial resources within the Polio Eradication and Endgame Strategic Plan timelines. In June 2014, the Polio Oversight Board (POB) agreed to make available a maximum envelope of US $45 million toward supporting countries not eligible for Gavi funding. This article describes the design of the funding mechanism that was developed, its implementation and the lessons learned through this process. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.
Halvorson, David A
Biosecurity is the first line of defence in the prevention and control of mildly pathogenic avian influenza (MPAI). Its use has been highly successful in keeping avian influenza (AI) out of commercial poultry worldwide. However, sometimes AI becomes introduced into poultry populations and, when that occurs, biosecurity again is the primary means of controlling the disease. There is agreement that routine serological monitoring, disease reporting, isolation or quarantine of affected flocks, application of strict measures to prevent the contamination of and movement of people and equipment, and changing flock schedules are necessities for controlling AI. There is disagreement as to the disposition of MPAI-infected flocks: some advocate their destruction and others advocate controlled marketing. Sometimes biosecurity is not enough to stop the spread of MPAI. In general, influenza virus requires a dense population of susceptible hosts to maintain itself. When there is a large population of susceptible poultry in an area, use of an inactivated AI vaccine can contribute to AI control by reducing the susceptibility of the population. Does use of inactivated vaccine assist, complicate or interfere with AI control and eradication? Yes, it assists MPAI control (which may reduce the risk of highly pathogenic AI (HPAI)) but, unless steps are taken to prevent it, vaccination may interfere with sero-epidemiology in the case of an HPAI outbreak. Does lack of vaccine assist, complicate or interfere with AI control and eradication? Yes, it assists in identification of sero-positive (convalescent) flocks in a HPAI eradication program, but it interferes with MPAI control (which in turn may increase the risk of emergence of HPAI).A number of hypothetical concerns have been raised about the use of inactivated AI vaccines. Infection of vaccinated flocks, serology complications and spreading of virus by vaccine crews are some of the hypothetical concerns. The discussion of these concerns
Seybil, V B; Malyshkina, L P; Ageeva, O T; Kosolapova, E I; Mnozhina, E G; Groshenkova, E V; Krivtsov, N V; Gurianova, N I; Daltsaeva, M K; Fomina, N S
The goal of this work was to estimate the collective immunity against poliomyelitis among the population of 8 regions and republics of Russia. The rates of the collective immunity against poliomyelitis allow the polio vaccination quality to be estimated and the population protection rate to be simultaneously demonstrated. A total of 8 regions (2138 people) were tested. The antibodies to the polioviruses of 1-3 types were determined against the vaccine Sabin strains in the neutralization test in the RD cell line. As a result, we found that vaccination against poliomyelitis in all observed regions was maintained at the required high level. Thus, the number of people with antibodies to the polio in most regions and age groups approximates or reaches 100%, while GMT is also high. This work demonstrated the necessity of the continuation of vaccination against poliomyelitis and control over collective immunity.
Wang, Fang; Zhang, Ming; Xie, Bing-Feng; Cao, Han; Tong, Shao-Yong; Wang, Jun-Rong; Yu, Xiao-Ping; Tang, Yang; Yang, Jing-Ran; Sun, Ming-Bo
To study the effect of aluminume adjuvant and immunization schedule on immunogenicity of Sabin inactivated poliovirus vaccine. Four batches of Sabin IPV were produced by different concentrations of type 1, 2, and 3 poliovirus and administrated on three-dose schedule at 0, 1, 2 months and 0, 2, 4 months on rats. Serum samples were collected one month after each dose and neutralizing antibody titers against three types poliovirus were determined by micro-neutralization assay. The GMTs of neutralizing antibodies against three types poliovirus increased significantly and the seropositivity rates were 100% in all groups after 3 doses. There was no significant difference between two immunization schedules, and the 0, 2, 4 month schedule could induce higher level neutralizing antibody compared to the 0, 1, 2 month schedule. The groups with aluminum adjuvant could induce higher level neutralizing antibody compared to the groups without adjuvant. Aluminum djuvant and immunization schedule could improve the immunogenicity of Sabin IPV.
Dong, S Z; Zhu, W B
Global polio eradication has entered its final phase, but still faces enormous challenges. The Polio Eradication and Endgame Strategic Plan (2013-2018) set the target for making the world polio-free by 2018. Meanwhile, the World Heath Organization Global Action Plan (GAP Ⅲ) recommended that polioviruses be stored under strict conditions after eradication of the wild poliovirus. At least one dose of inactivated poliovirus vaccine (IPV) would be required for each newborn baby in the world to ensure successful completion of the final strategy and GAP Ⅲ. The Sabin IPV has a high production safety and low production cost, compared with the wild-virus IPV and, therefore, can play an important role in the final stage of global polio eradication.
Abdallah, Fatma; Hassanin, Ola
Avian Influenza (AI) vaccines are widely used for mammals and birds in a trial to eliminate the Avian Influenza virus (AIV) infection from the world. However and up till now the virus is still existed via modulation of its antigenic structure to evade the pressure of host immune responses. For a complete understanding of the immune responses following AI vaccination in chickens, the modulations of the chickens humoral immune responses and interferon-alpha signaling pathway, as a fundamental part of the innate immune responses, were investigated. In our study, we measured the humoral immune response using hemagglutination-inhibition (HI) and enzyme-linked immunosorbent assay (ELISA) tests. In addition, chicken interferon-alpha pathway components was measured at RNA levels using Quantitative Real-time PCR (qRT-PCR) following one dose of inactivated H5N1 influenza vaccine at 14 days of age. In this study, the protective levels of humoral antibody responses were observed at 14, 21 and 28 days following immunization with inactivated (Re-1/H5N1) AI vaccine. In the chicken spleen cells, up regulation in the chicken interferon-alpha pathway components (MX1 & IRF7) was existed as early as 48 h post vaccination and remained until 28 days post vaccination at the endogenous state. However, after the recall with ex-vivo stimulation, the up regulation was more pronounced in the transcriptional factor (IRF7) compared to the antiviral gene (MX1) at 28 days post vaccination. So far, from our results it appears that the inactivated H5N1 vaccine can trigger the chicken interferon-alpha signaling pathway as well as it can elicit protective humoral antibody responses.
Fan, Yunpeng; Ma, Xia; Hou, Weifeng; Guo, Chao; Zhang, Jing; Zhang, Weimin; Ma, Lin; Song, Xiaoping
In this study, the adjuvant activity of ophiopogon polysaccharide liposome (OPL) was investigated. The effects of OPL on the splenic lymphocyte proliferation of mice were measured in vitro. The results showed that OPL could significantly promote lymphocyte proliferation singly or synergistically with PHA and LPS and that the effect was better than ophiopogon polysaccharide (OP) at most of concentrations. The adjuvant activities of OPL, OP and mineral oil were compared in BALB/c mice inoculated with inactivated PPV in vivo. The results showed that OPL could significantly enhance lymphocyte proliferation, increase the proportion of CD4(+) and CD8(+) T cells, improve the HI antibody titre and specific IgG response, and promote the production of cytokines, and the efficacy of OPL was significantly better than that of OP. In addition, OPL significantly improved the cellular immune response compared with oil adjuvant. These results suggested that OPL possess superior adjuvanticity and that a medium dose had the best efficacy. Therefore, OPL can be used as an effective immune adjuvant for an inactivated PPV vaccine. Copyright © 2015. Published by Elsevier B.V.
Gaetano Federico Ronchi
Full Text Available Monovalent, inactivated and adjuvanted vaccines against African horse sickness, prepared with serotypes 5 and 9, were tested on guinea-pigs to select the formulation that offered the greatest immunity. The final formulation of the vaccines took into account the immune response in the guinea-pig and the inflammatory properties of two types of adjuvant previously tested on target animals. A pilot study was subsequently conducted on horses using a vaccine prepared with serotype 9. The vaccine stimulated neutralising antibodies from the first administration and, after the booster dose, 28 days later; high antibody levels were recorded for at least 10 months. The guinea-pig appears to be a useful laboratory model for the evaluation of the antigenic properties of African horse sickness vaccines.
Yuk, Seong-Su; To, Eredene-Ochir; Kwon, Jung-Hoon; Noh, Jin-Yong; Hong, Woo-Tack; Jeong, Jei-Hyun; Gwon, Gyeong-Bin; Song, Chang-Seon
Owing to the increase in the number of diseases affecting ducks and the demand for food safety by consumers, vaccination has become one of the factors that influence duck meat productivity. The highly pathogenic avian influenza (HPAI) virus is one of the most prevalent and causes one of the most lethal diseases in domestic ducks, and Salmonella enterica serovar Typhimurium is a food-borne pathogen persistent in the domestic duck population. To better understand the optimal usage of HPAI and S. enterica serovar Typhimurium vaccines, we aimed to determine antigen dose, oil and gel adjuvant usage with prime-boost regimen, and vaccination age, inducing the best immune response in ducks, without an effect on body weight gain. In the case of the inactivated H5N9 vaccine, a single dose of vaccine was inadequate to induce proper antibody titer when administered to day-old ducks, which necessitates boost vaccination. Administration of the oil-adjuvanted H5N9 vaccine administration in day-old and 2-week-old ducks resulted in a lower body weight at the time of slaughtering, compared to that of gel-adjuvanted H5N9 vaccine. However, gel-adjuvanted H5N9 vaccine failed to induce proper immune response to an extent recommend by OIE-World Organization for Animal Health. In the case of the Salmonella enterica serovar Typhimurium vaccine, a moderate or low dose of vaccine was appropriate for day-old ducks receiving the gel prime-oil boost vaccination. Single vaccination with oil adjuvants affects the mean body weight of 7-week-old ducks, suggesting that the gel adjuvant is more suitable for meat production. We expect that the use of adjuvants in a prime-boost regimen and at antigen doses set in this study will be helpful to maximize body weight in the case of domestic duck production at the actual farm site. © 2017 Poultry Science Association Inc.
O'Ryan, Miguel; Bandyopadhyay, Ananda S; Villena, Rodolfo; Espinoza, Mónica; Novoa, José; Weldon, William C; Oberste, M Steven; Self, Steve; Borate, Bhavesh R; Asturias, Edwin J; Clemens, Ralf; Orenstein, Walter; Jimeno, José; Rüttimann, Ricardo; Costa Clemens, Sue Ann
Bivalent oral poliovirus vaccine (bOPV; types 1 and 3) is expected to replace trivalent OPV (tOPV) globally by April, 2016, preceded by the introduction of at least one dose of inactivated poliovirus vaccine (IPV) in routine immunisation programmes to eliminate vaccine-associated or vaccine-derived poliomyelitis from serotype 2 poliovirus. Because data are needed on sequential IPV-bOPV schedules, we assessed the immunogenicity of two different IPV-bOPV schedules compared with an all-IPV schedule in infants. We did a randomised, controlled, open-label, non-inferiority trial with healthy, full-term (>2·5 kg birthweight) infants aged 8 weeks (± 7 days) at six well-child clinics in Santiago, Chile. We used supplied lists to randomly assign infants (1:1:1) to receive three polio vaccinations (IPV by injection or bOPV as oral drops) at age 8, 16, and 24 weeks in one of three sequential schedules: IPV-bOPV-bOPV, IPV-IPV-bOPV, or IPV-IPV-IPV. We did the randomisation with blocks of 12 stratified by study site. All analyses were done in a masked manner. Co-primary outcomes were non-inferiority of the bOPV-containing schedules compared with the all-IPV schedule for seroconversion (within a 10% margin) and antibody titres (within two-thirds log2 titres) to poliovirus serotypes 1 and 3 at age 28 weeks, analysed in the per-protocol population. Secondary outcomes were seroconversion and titres to serotype 2 and faecal shedding for 4 weeks after a monovalent OPV type 2 challenge at age 28 weeks. Safety analyses were done in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01841671, and is closed to new participants. Between April 25 and August 1, 2013, we assigned 570 infants to treatment: 190 to IPV-bOPV-bOPV, 192 to IPV-IPV-bOPV, and 188 to IPV-IPV-IPV. 564 (99%) were vaccinated and included in the intention-to-treat cohort, and 537 (94%) in the per-protocol analyses. In the IPV-bOPV-bOPV, IPV-IPV-bOPV, and IPV-IPV-IPV groups
Dolka, Beata; Żbikowski, Artur; Dolka, Izabella; Szeleszczuk, Piotr
Recent epidemics of highly pathogenic avian influenza (HPAI) produced an unprecedented number of cases in mute swans (Cygnus olor) in European countries, which indicates that these birds are very sensitive to the H5N1 virus. The HPAI outbreaks stirred a debate on the controversial stamping-out policy in populations of protected bird species. After preventive vaccination had been approved in the European Union, several countries have introduced vaccination schemes to protect poultry, captive wild birds or exotic birds in zoos against HPAI. The aim of this study was to investigate the immune response of wild mute swans to immunization with an inactivated AI H5N2 vaccine approved for use in poultry. The serological responses of mute swans were assessed by comparison with racing pigeons (Columba livia), a species which is characterized by different susceptibility to infection with the H5N1 HPAI virus and plays a questionable role in the ecology of influenza (H5N1) viruses. Swans were vaccinated once or twice at an interval of 4 weeks. The humoral immune response was evaluated by hemagglutination inhibition (HI) and NP-ELISA. The lymphocyte blast transformation test was used to determine the cell-mediated immune response. Higher values of the geometric mean titer (GMT) and 100 % seroconversion (HI ≥32) were noted in double vaccinated swans (1448.2) than in single vaccinated swans (128.0) or in double vaccinated pigeons (215.3). Significant differences in HI titers were observed between swans and pigeons, but no variations in ELISA scores were noted after the booster dose. Immunization of swans had no effect on the proliferative activity of lymphocytes. The inactivated H5N2 vaccine was safe and immunogenic for mute swans and pigeons. Vaccination may have practical implications for swans kept in zoos, wildlife parks or rehabilitation centers. However, challenge studies are needed to prove the efficacy of the H5N2 AI vaccine.
Jarrahian, Courtney; Rein-Weston, Annie; Saxon, Gene; Creelman, Ben; Kachmarik, Greg; Anand, Abhijeet; Zehrung, Darin
Intradermal delivery of a fractional dose of inactivated poliovirus vaccine (IPV) offers potential benefits compared to intramuscular (IM) delivery, including possible cost reductions and easing of IPV supply shortages. Objectives of this study were to assess intradermal delivery devices for dead space, wastage generated by the filling process, dose accuracy, and total number of doses that can be delivered per vial. Devices tested included syringes with staked (fixed) needles (autodisable syringes and syringes used with intradermal adapters), a luer-slip needle and syringe, a mini-needle syringe, a hollow microneedle device, and disposable-syringe jet injectors with their associated filling adapters. Each device was used to withdraw 0.1-mL fractional doses from single-dose IM glass vials which were then ejected into a beaker. Both vial and device were weighed before and after filling and again after expulsion of liquid to record change in volume at each stage of the process. Data were used to calculate the number of doses that could potentially be obtained from multidose vials. Results show wide variability in dead space, dose accuracy, overall wastage, and total number of doses that can be obtained per vial among intradermal delivery devices. Syringes with staked needles had relatively low dead space and low overall wastage, and could achieve a greater number of doses per vial compared to syringes with a detachable luer-slip needle. Of the disposable-syringe jet injectors tested, one was comparable to syringes with staked needles. If intradermal delivery of IPV is introduced, selection of an intradermal delivery device can have a substantial impact on vaccine wasted during administration, and thus on the required quantity of vaccine that needs to be purchased. An ideal intradermal delivery device should be not only safe, reliable, accurate, and acceptable to users and vaccine recipients, but should also have low dead space, high dose accuracy, and low overall
Heba M. El Naggar
Full Text Available Aim: To develop a mucosal inactivated vaccines for Newcastle disease (ND and H9N2 viruses to protect against these viruses at sites of infections through mucosal immunity. Materials and Methods: In this study, we prepared two new formulations for mucosal bivalent inactivated vaccine formulations for Newcastle and Avian Influenza (H9N2 based on the use of nanoparticles and polymer adjuvants. The prepared vaccines were delivered via intranasal and spray routes of administration in specific pathogen-free chickens. Cell-mediated and humoral immune response was measured as well as challenge trial was carried out. In addition, ISA71 water in oil was also evaluated. Results: Our results showed that the use of spray route as vaccination delivery method of polymer and nanoparticles MontanideTM adjuvants revealed that it enhanced the cell mediated immune response as indicated by phagocytic activity, gamma interferon and interleukin 6 responses and induced protection against challenge with Newcastle and Avian Influenza (H9N2 viruses. Conclusion: The results of this study demonstrate the potentiality of polymer compared to nanoparticles adjuvantes when used via spray route. Mass application of such vaccines will add value to improve the vaccination strategies against ND virus and Avian influenza viruses.
Co-administration of live measles and yellow fever vaccines and inactivated pentavalent vaccines is associated with increased mortality compared with measles and yellow fever vaccines only. An observational study from Guinea-Bissau.
Fisker, Ane Bærent; Ravn, Henrik; Rodrigues, Amabelia; Østergaard, Marie Drivsholm; Bale, Carlito; Benn, Christine Stabell; Aaby, Peter
Studies from low-income countries indicate that co-administration of inactivated diphtheria-tetanus-pertussis (DTP) vaccine and live attenuated measles vaccine (MV) is associated with increased mortality compared with receiving MV only. Pentavalent (DTP-H. Influenza type B-Hepatitis B) vaccine is replacing DTP in many low-income countries and yellow fever vaccine (YF) has been introduced to be given together with MV. Pentavalent and YF vaccines were introduced in Guinea-Bissau in 2008. We investigated whether co-administration of pentavalent vaccine with MV and yellow fever vaccine has similar negative effects. In 2007-2011, we conducted a randomised placebo-controlled trial of vitamin A at routine vaccination contacts among children aged 6-23 months in urban and rural Guinea-Bissau. In the present study, we included 2331 children randomised to placebo who received live vaccines only (MV or MV+YF) or a combination of live and inactivated vaccines (MV+DTP or MV+YF+pentavalent). Mortality was compared in Cox proportional hazards models stratified for urban/rural enrolment adjusted for age and unevenly distributed baseline factors. While DTP was still used 685 children received MV only and 358 MV+DTP; following the change in programme, 940 received MV+YF only and 348 MV+YF+pentavalent. During 6 months of follow-up, the adjusted mortality rate ratio (MRR) for co-administered live and inactivated vaccines compared with live vaccines only was 3.24 (1.20-8.73). For MV+YF+pentavalent compared with MV+YF only, the adjusted MRR was 7.73 (1.79-33.4). In line with previous studies of DTP, the present results indicate that pentavalent vaccine co-administered with MV and YF is associated with increased mortality. Copyright © 2013 Elsevier Ltd. All rights reserved.
Okayasu, Hiromasa; Sein, Carolyn; Hamidi, Ahd; Bakker, Wilfried A M; Sutter, Roland W
The Global Polio Eradication Initiative (GPEI) has seen significant progress since it began in 1988, largely due to the worldwide use of oral poliovirus vaccine (OPV). In order to achieve polio eradication the global cessation of OPV is necessary because OPV contains live attenuated poliovirus, which in rare circumstances could re-gain wild poliovirus (WPV) characteristics with potential to establish transmission. The GPEI endgame strategy for the period 2013-2018 recommends the globally synchronised sequential cessation of the Sabin strains contained in the OPV, starting with type 2 Sabin. The withdrawal of Sabin type 2 took place in April 2016, with the introduction of at least one dose of inactivated poliovirus vaccine (IPV) as a risk mitigation strategy. The introduction of IPV into 126 countries since 2013 has required a rapid scale-up of IPV production by the two manufacturers supplying the global public sector market. This scale-up has been fraught with challenges, resulting in reductions of 40-50% of initial supply commitments. Consequently, 22 countries will not be supplied until 2018, and another 23 countries will experience serious stock-outs. In the last decade repeated calls-for-action were made to the global community to invigorate their vision and investment in developing "new poliovirus vaccines" including the development of IPV from less-virulent strains, such as Sabin-IPV (S-IPV). The conventional Salk-IPV production is limited to high-income industrialized-country manufacturers due to the containment requirements (i.e., high sanitation, low force-of-poliovirus-infection, and high population immunity). The use of Sabin strains in the production of S-IPV carries a lower biosafety risk, and was determined to be suitable for production in developing countries, expanding the manufacturing base and making IPV more affordable and accessible in the long term. Significant progress in the S-IPV has been made since 2006. S-IPV is now licensed as S-IPV in
Kanojia, Gaurav; Ten Have, Rimko; Brugmans, Debbie; Soema, Peter C; Frijlink, Henderik W; Amorij, Jean-Pierre; Kersten, Gideon
The objective of this study was to develop a stable spray dried formulation, containing the three serotypes of Sabin inactivated polio vaccine (sIPV), aiming for minimal loss of native conformation (D-antigen) during drying and subsequent storage. The influence of atomization and drying stress during spray drying on trivalent sIPV was investigated. This was followed by excipient screening, in which monovalent sIPV was formulated and spray dried. Excipient combinations and concentrations were tailored to maximize both the antigen recovery of respective sIPV serotypes after spray drying and storage (T= 40°C and t= 7 days). Furthermore, a fractional factorial design was developed around the most promising formulations to elucidate the contribution of each excipient in stabilizing D-antigen during drying. Serotype 1 and 2 could be dried with 98 % and 97 % recovery, respectively. When subsequently stored at 40°C for 7 days, the D-antigenicity of serotype 1 was fully retained. For serotype 2 the D-antigenicity dropped to 71 %. Serotype 3 was more challenging to stabilize and a recovery of 56 % was attained after drying, followed by a further loss of 37 % after storage at 40°C for 7 days. Further studies using a design of experiments approach demonstrated that trehalose/monosodium glutamate and maltodextrin/arginine combinations were crucial for stabilizing serotype 1 and 2, respectively. For sIPV serotype 3, the best formulation contained Medium199, glutathione and maltodextrin. For the trivalent vaccine it is therefore probably necessary to spray dry the different serotypes separately and mix the dry powders afterwards to obtain the trivalent vaccine. Copyright © 2018. Published by Elsevier B.V.
Kornreich, L. [Imaging Department, The Schneider Children`s Medical Centre of Israel, Kaplan Street, Petah Tiqva 49202 (Israel)]|[Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv (Israel); Dagan, O. [The Intensive Care Unit, The Schneider Children`s Medical Centre of Israel, Beilinson Medical Campus, Petah Tiqva (Israel)]|[Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv (Israel); Grunebaum, M. [Imaging Department, The Schneider Children`s Medical Centre of Israel, Kaplan Street, Petah Tiqva 49202 (Israel)]|[Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv (Israel)
MRI can be used in the diagnosis of anterior horn infection and for assessing the extent of disease. There are no specific MRI signs to differentiate between the various possible pathogens. This is demonstrated in the present case of poliomyelitis, in which MRI of the spine played an important role in establishing the diagnosis. (orig.). With 1 fig.
Full Text Available The article deals with the problem of poliomyelitis in children. The history of this disease and the current state of morbidity in Ukraine are considered. The features of the clinical pattern in children are described. Diagnostic criteria and treatment methods are presented.
Kornreich, L.; Dagan, O.; Grunebaum, M.
MRI can be used in the diagnosis of anterior horn infection and for assessing the extent of disease. There are no specific MRI signs to differentiate between the various possible pathogens. This is demonstrated in the present case of poliomyelitis, in which MRI of the spine played an important role in establishing the diagnosis. (orig.). With 1 fig
Wu, Wendi; Liu, Dawei; Li, Keli; Nuorti, J Pekka; Nohynek, Hanna M; Xu, Disha; Ye, Jiakai; Zheng, Jingshan; Wang, Huaqing
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.
WHO Working Group discussion on revision of the WHO recommendations for the production and control of poliomyelitis vaccines (oral): TRS Nos. 904 and 910. Report of Meeting held on 20-22 July 2010, Geneva, Switzerland.
Martin, Javier; Milne, Catherine; Minor, Philip; Chumakov, Konstantin; Baca-Estrada, Maria; Caruana, Jacqueline Fournier; Zhou, Tiequn
Oral poliomyelitis vaccine (OPV) is a critical part of the polio eradication programme. A high number of doses are administered each year with an impact on billions of citizens worldwide. It is therefore essential that written standards concerning OPV are up to date and widely available. The World Health Organization (WHO) publishes technical guidance on the quality, safety and efficacy of vaccines intended to assist national regulatory authorities (NRAs), national control laboratories (NCLs) and manufacturers. As part of its programme, on 20-22 July 2010 WHO convened a working group meeting to initiate the revision of the WHO recommendations on the production and control of OPV as presently outlined in the Technical Reports Series (TRS) issues Nos. 904 and 910 [1,2]. The attendees included experts from academia, NRAs/NCLs and industry involved in the study, manufacture, and authorization and testing/release of OPV from countries around the world including representatives from China, the European Union, Indonesia, Japan, Mexico, and the USA. The objective was to review the state of knowledge concerning production and control of OPV, with a focus on neurovirulence testing, to determine how the existing guidelines should be updated and what recommendations should be made for the future. The outcomes of this meeting will be taken into consideration in future revision of the WHO TRS. Copyright © 2011. Published by Elsevier Ltd.. All rights reserved.
Kotloff, Karen L.; Halasa, Natasha B.; Harrison, Christopher J.; Englund, Janet A.; Walter, Emmanuel B.; King, James C.; Creech, C. Buddy; Healy, Sara A.; Dolor, Rowena J.; Stephens, Ina; Edwards, Kathryn M.; Noah, Diana L.; Hill, Heather; Wolff, Mark
Background As the influenza AH1N1 pandemic emerged in 2009, children were found to experience high morbidity and mortality and were prioritized for vaccination. This multicenter, randomized, double-blind, age-stratified trial assessed the safety and immunogenicity of inactivated influenza A(H1N1)pdm09 vaccine in healthy children aged 6 months to 17 years. Methods Children received two doses of approximately 15 μg or 30 μg hemagglutin antigen 21 days apart. Reactogenicity was assessed for 8 days after each dose, adverse events through day 42, and serious adverse events or new-onset chronic illnesses through day 201. Serum hemagglutination inhibition (HAI) titers were measured on days 0 (pre-vaccination), 8, 21, 29, and 42. Results A total of 583 children received the first dose and 571 received the second dose of vaccine. Vaccinations were generally well-tolerated and no related serious adverse events were observed. The 15 μg dosage elicited a seroprotective HAI (≥1:40) in 20%, 47%, and 93% of children in the 6-35 month, 3-9 year, and 10-17 year age strata 21 days after dose 1 and in 78%, 82%, and 98% of children 21 days after dose 2, respectively. The 30 μg vaccine dosage induced similar responses. Conclusions The inactivated influenza A(H1N1)pdm09 vaccine exhibited a favorable safety profile at both dosage levels. While a single 15 or 30 μg dose induced seroprotective antibody responses in most 10-17 year olds, younger children required 2 doses, even when receiving dosages 4-6 fold higher than recommended. Well-tolerated vaccines are needed that induce immunity after a single dose for use in young children during influenza pandemics. PMID:25222307
Caridi, Flavia; Vázquez-Calvo, Ángela; Borrego, Belén; McCullough, Kenneth; Summerfield, Artur; Sobrino, Francisco; Martín-Acebes, Miguel A
Foot-and-mouth disease virus (FMDV) is the etiological agent of a highly contagious disease that affects important livestock species. Vaccines based on inactivated FMDV virions provide a useful tool for the control of this pathogen. However, long term storage at 4°C (the temperature for vaccine storage) or ruptures of the cold chain, provoke the dissociation of virions, reducing the immunogenicity of the vaccine. An FMDV mutant carrying amino acid replacements VP1 N17D and VP2 H145Y isolated previously rendered virions with increased resistance to dissociation at 4°C. We have evaluated the immunogenicity in swine (a natural FMDV host) of a chemically inactivated vaccine based on this mutant. The presence of these amino acid substitutions did not compromise the immunological potential, including its ability to elicit neutralizing antibodies. These results support the feasibility of this kind of mutants with increased capsid stability as suitable viruses for producing improved FMDV vaccines. Copyright © 2017 Elsevier B.V. All rights reserved.
Halperin, Scott A; Smith, Bruce; Mabrouk, Taoufik; Germain, Marc; Trépanier, Pierre; Hassell, Thomas; Treanor, John; Gauthier, Richard; Mills, Elaine L
We performed randomized, double-blind, controlled trials to assess the safety and immunogenicity of an inactivated, Madin Darby Canine Kidney (MDCK)-derived cell line produced influenza vaccine in healthy adults (19-50 years), children (3-12 years) and the elderly (> or =65 years). We studied three lots of cell culture-derived vaccine and one lot of licensed egg-derived vaccine in healthy adults (n=462), two lots of cell culture-derived vaccine and one lot of egg-derived vaccine in seniors (n=269), and one lot of each vaccine in children (n=209). Adverse events were collected during the first 3 days post-immunization; serum was collected before and 1 month after immunization. Rates of local and systemic adverse reactions were similar with both vaccines. An injection site adverse event rated at least moderate severity was reported by 21.9% of children who received the egg-derived vaccine and 25.0% of those who received the cell culture-derived vaccine. In healthy adults the proportions were 12.1 and 15.3%, respectively and 6.7 and 6.3%, respectively in seniors. Systemic events of at least moderate severity were 12.4 and 12.5% in children, 19.8 and 13.6% in healthy adults, and 14.1 and 9.7% in seniors; none of these differences were statistically significant. The antibody response against all three viruses was similar between the two vaccines. From 83 to 100% of children, healthy adults and seniors achieved hemagglutination inhibition titers in excess of 40 post-immunization. We conclude that the cell culture-derived vaccine was safe and immunogenic in children, healthy adults and seniors.
Immunogenicity and safety of combined adsorbed low-dose diphtheria, tetanus and inactivated poliovirus vaccine (REVAXIS®) versus combined diphtheria, tetanus and inactivated poliovirus vaccine (DT Polio®) given as a booster dose at 6 years of age
Gajdos, Vincent; Soubeyrand, Benoit; Vidor, Emmanuel; Richard, Patrick; Boyer, Julie; Sadorge, Christine
This randomized, comparative, phase-IIIb study conducted in France aimed to demonstrate whether seroprotection against diphtheria, tetanus and poliomyelitis 1 month after a single dose of REVAXIS (low-dose diphtheria) is non-inferior to seroprotection 1 month after a single dose of DT Polio (standard-dose diphtheria), both vaccines being given as a second booster to healthy children at 6 years of age. Children were randomly assigned to receive a single intramuscular dose of REVAXIS or DT Polio. Primary endpoints were the 1-month post-booster seroprotection rates for diphtheria, tetanus and poliovirus type-1, -2 and -3 antigens. Secondary endpoints were immunogenicity and safety observations. Of 788 children screened, 760 were randomized: REVAXIS group, 384 children; DT Polio group, 376 children. No relevant difference in demographic characteristics at baseline was observed between REVAXIS and DT Polio groups. Noninferiority of REVAXIS compared with DT Polio for seroprotection was demonstrated against diphtheria (respectively 98.6% and 99.3%), tetanus (respectively 99.6% and 100%) and poliovirus antigens (100% for each types in both groups). No allergic reactions to REVAXIS were reported. A benefit/risk ratio in favor of REVAXIS was suggested by the trend towards a better tolerability of REVAXIS compared with DT Polio regarding the rate of severe solicited injection-site reactions. The results support the use of REVAXIS as a booster at 6 years of age in infants who previously received a three-dose primary series within the first 6 months of life and a first booster including diphtheria, tetanus and poliovirus vaccine(s) given before 2 years of age. PMID:21441781
Eggers, Maren; Terletskaia-Ladwig, Elena; Rabenau, Holger F; Doerr, Hans W; Diedrich, Sabine; Enders, Gisela; Enders, Martin
In October 2007, the working group CEN/TC 216 of the European Committee for standardisation suggested that the Sabin oral poliovirus vaccine type 1 strain (LSc-2ab) presently used for virucidal tests should be replaced by another attenuated vaccine poliovirus type 1 strain, CHAT. Both strains were historically used as oral vaccines, but the Sabin type 1 strain was acknowledged to be more attenuated. In Germany, vaccination against poliomyelitis was introduced in 1962 using the oral polio vaccine (OPV) containing Sabin strain LSc-2ab. The vaccination schedule was changed from OPV to an inactivated polio vaccine (IPV) containing wild polio virus type 1 strain Mahoney in 1998. In the present study, we assessed potential differences in neutralising antibody titres to Sabin and CHAT in persons with a history of either OPV, IPV, or OPV with IPV booster. Neutralisation poliovirus antibodies against CHAT and Sabin 1 were measured in sera of 41 adults vaccinated with OPV. Additionally, sera from 28 children less than 10 years of age and immunised with IPV only were analysed. The neutralisation assay against poliovirus was performed according to WHO guidelines. The neutralisation activity against CHAT in adults with OPV vaccination history was significantly lower than against Sabin poliovirus type 1 strains (Wilcoxon signed-rank test P Sabin 1 varied between 8 and 64. Following IPV booster, anti-CHAT antibodies increased rapidly in sera of CHAT-negative adults with OPV history. Sera from children with IPV history neutralised CHAT and Sabin 1 strains equally. The lack of neutralising antibodies against the CHAT strain in persons vaccinated with OPV might be associated with an increased risk of reinfection with the CHAT polio virus type 1, and this implies a putative risk of transmission of the virus to polio-free communities. We strongly suggest that laboratory workers who were immunised with OPV receive a booster vaccination with IPV before handling CHAT in the laboratory.
Full Text Available Abstract Background In October 2007, the working group CEN/TC 216 of the European Committee for standardisation suggested that the Sabin oral poliovirus vaccine type 1 strain (LSc-2ab presently used for virucidal tests should be replaced by another attenuated vaccine poliovirus type 1 strain, CHAT. Both strains were historically used as oral vaccines, but the Sabin type 1 strain was acknowledged to be more attenuated. In Germany, vaccination against poliomyelitis was introduced in 1962 using the oral polio vaccine (OPV containing Sabin strain LSc-2ab. The vaccination schedule was changed from OPV to an inactivated polio vaccine (IPV containing wild polio virus type 1 strain Mahoney in 1998. In the present study, we assessed potential differences in neutralising antibody titres to Sabin and CHAT in persons with a history of either OPV, IPV, or OPV with IPV booster. Methods Neutralisation poliovirus antibodies against CHAT and Sabin 1 were measured in sera of 41 adults vaccinated with OPV. Additionally, sera from 28 children less than 10 years of age and immunised with IPV only were analysed. The neutralisation assay against poliovirus was performed according to WHO guidelines. Results The neutralisation activity against CHAT in adults with OPV vaccination history was significantly lower than against Sabin poliovirus type 1 strains (Wilcoxon signed-rank test P Conclusion The lack of neutralising antibodies against the CHAT strain in persons vaccinated with OPV might be associated with an increased risk of reinfection with the CHAT polio virus type 1, and this implies a putative risk of transmission of the virus to polio-free communities. We strongly suggest that laboratory workers who were immunised with OPV receive a booster vaccination with IPV before handling CHAT in the laboratory.
Full Text Available Annually, swine influenza A virus (SwIAV causes severe economic loss to swine industry. Currently used inactivated SwIAV vaccines administered by intramuscular injection provide homologous protection, but limited heterologous protection against constantly evolving field viruses, attributable to the induction of inadequate levels of mucosal IgA and cellular immune responses in the respiratory tract. A novel vaccine delivery platform using mucoadhesive chitosan nanoparticles (CNPs administered through intranasal (IN route has the potential to elicit strong mucosal and systemic immune responses in pigs. In this study, we evaluated the immune responses and cross-protective efficacy of IN chitosan encapsulated inactivated SwIAV vaccine in pigs. Killed SwIAV H1N2 (δ-lineage antigens (KAg were encapsulated in chitosan polymer-based nanoparticles (CNPs-KAg. The candidate vaccine was administered twice IN as mist to nursery pigs. Vaccinates and controls were then challenged with a zoonotic and virulent heterologous SwIAV H1N1 (γ-lineage. Pigs vaccinated with CNPs-KAg exhibited an enhanced IgG serum antibody and mucosal secretory IgA antibody responses in nasal swabs, bronchoalveolar lavage (BAL fluids, and lung lysates that were reactive against homologous (H1N2, heterologous (H1N1, and heterosubtypic (H3N2 influenza A virus strains. Prior to challenge, an increased frequency of cytotoxic T lymphocytes, antigen-specific lymphocyte proliferation, and recall IFN-γ secretion by restimulated peripheral blood mononuclear cells in CNPs-KAg compared to control KAg vaccinates were observed. In CNPs-KAg vaccinated pigs challenged with heterologous virus reduced severity of macroscopic and microscopic influenza-associated pulmonary lesions were observed. Importantly, the infectious SwIAV titers in nasal swabs [days post-challenge (DPC 4] and BAL fluid (DPC 6 were significantly (p < 0.05 reduced in CNPs-KAg vaccinates but not in KAg vaccinates when compared
Zipursky, Simona; Patel, Manish; Farrell, Margaret; Gonzalez, Alejandro Ramirez; Kachra, Tasleem; Folly, Yann; Kurji, Feyrouz; Veira, Chantal Laroche; Wootton, Emily; Hampton, Lee M
The Immunization Systems Management Group (IMG) was established as a time-limited entity, responsible for the management and coordination of Objective 2 of the Polio Eradication and Endgame Strategic Plan. This objective called for the introduction of at least 1 dose of inactivated polio vaccine (IPV) into the routine immunization programs of all countries using oral polio vaccine (OPV) only. Despite global vaccine shortages, which limited countries' abilities to access IPV in a timely manner, 105 of 126 countries using OPV only introduced IPV within a 2.5-year period, making it the fastest rollout of a new vaccine in history. This achievement can be attributed to several factors, including the coordination work of the IMG; high-level engagement and advocacy across partners; the strong foundations of the Expanded Programme on Immunization at all levels; Gavi, the Vaccine Alliance's vaccine introduction experiences and mechanisms; innovative approaches; and proactive communications. In many ways, the IMG's work on IPV introduction can serve as a model for other vaccine introductions, especially in an accelerated context. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.
Muller, David A; Pearson, Frances E; Fernando, Germain J P; Agyei-Yeboah, Christiana; Owens, Nick S; Corrie, Simon R; Crichton, Michael L; Wei, Jonathan C J; Weldon, William C; Oberste, M Steven; Young, Paul R; Kendall, Mark A F
Polio eradication is progressing rapidly, and the live attenuated Sabin strains in the oral poliovirus vaccine (OPV) are being removed sequentially, starting with type 2 in April 2016. For risk mitigation, countries are introducing inactivated poliovirus vaccine (IPV) into routine vaccination programs. After April 2016, monovalent type 2 OPV will be available for type 2 outbreak control. Because the current IPV is not suitable for house-to-house vaccination campaigns (the intramuscular injections require health professionals), we developed a high-density microprojection array, the Nanopatch, delivered monovalent type 2 IPV (IPV2) vaccine to the skin. To assess the immunogenicity of the Nanopatch, we performed a dose-matched study in rats, comparing the immunogenicity of IPV2 delivered by intramuscular injection or Nanopatch immunisation. A single dose of 0.2 D-antigen units of IPV2 elicited protective levels of poliovirus antibodies in 100% of animals. However, animals receiving IPV2 by IM required at least 3 immunisations to reach the same neutralising antibody titres. This level of dose reduction (1/40th of a full dose) is unprecedented for poliovirus vaccine delivery. The ease of administration coupled with the dose reduction observed in this study points to the Nanopatch as a potential tool for facilitating inexpensive IPV for mass vaccination campaigns.
Shin, Ju-Hyung; Noh, Jin-Yong; Kim, Kwon-Ho; Park, Jae-Keun; Lee, Ji-Ho; Jeong, Seong Dong; Jung, Dae-Yoon; Song, Chang-Seon; Kim, Yeu-Chun
Microneedles are the micrometer size devices used for the delivery of vaccines and biotherapeutics. In order to increase the vaccine efficacy and reduce the antigen dose, there is a significant need to find some adjuvants for the microneedle vaccination. In this study, zymosan, which is the cell wall preparation of Saccharomyces cerevisiae, or poly (I:C) was coated on a microneedle with inactivated influenza virus, and then immunized into BALB/c mouse to determine the immunogenicity, protection and synergetic effect between two adjuvants. As a result, the group administered with zymosan and vaccine antigen showed significantly stronger IgG response, HI titer and IgG subtypes without any adverse effects, compared to the group immunized with the vaccine antigen alone. Also, there were enhanced cellular immune responses in the group received adjuvant with vaccine antigen. In addition, they showed superior protection and lung viral reduction against lethal viral challenge. Taken together, this study confirms that zymosan can be used as an immunostimulant for microneedle vaccination. Copyright © 2017 Elsevier B.V. All rights reserved.
Nathanson, Neal; Kew, Olen M.
Poliomyelitis has appeared in epidemic form, become endemic on a global scale, and been reduced to near-elimination, all within the span of documented medical history. Epidemics of the disease appeared in the late 19th century in many European countries and North America, following which polio became a global disease with annual epidemics. During the period of its epidemicity, 1900–1950, the age distribution of poliomyelitis cases increased gradually. Beginning in 1955, the creation of poliovirus vaccines led to a stepwise reduction in poliomyelitis, culminating in the unpredicted elimination of wild polioviruses in the United States by 1972. Global expansion of polio immunization resulted in a reduction of paralytic disease from an estimated annual prevaccine level of at least 600,000 cases to fewer than 1,000 cases in 2000. Indigenous wild type 2 poliovirus was eradicated in 1999, but unbroken localized circulation of poliovirus types 1 and 3 continues in 4 countries in Asia and Africa. Current challenges to the final eradication of paralytic poliomyelitis include the continued transmission of wild polioviruses in endemic reservoirs, reinfection of polio-free areas, outbreaks due to circulating vaccine-derived polioviruses, and persistent excretion of vaccine-derived poliovirus by a few vaccinees with B-cell immunodeficiencies. Beyond the current efforts to eradicate the last remaining wild polioviruses, global eradication efforts must safely navigate through an unprecedented series of endgame challenges to assure the permanent cessation of all human poliovirus infections. PMID:20978089
Vashishtha, Vipin M; Kamath, Sachidanand
Poliomyelitis, a dreaded disease of the last century that had already crippled millions of people across the globe, is now on the verge of eradication thanks mainly to two polio vaccines, inactivated polio vaccine (IPV) and oral polio vaccine (OPV). Ever since their development in late 1950s and early 1960s, the journey of their early development process, clinical trials, licensure and ultimately widespread clinical use in different countries provide a fascinating tale of events. Oral polio vaccine has been the mainstay of global polio eradication initiative (GPEI) in most of the countries. With the advent of 'polio endgame', the focus has now shifted back to IPV. However, there are certain issues associated with global cessation of OPV use and universal implementation of IPV in routine immunization schedules across the globe that need to be dealt with some urgency, before proclaiming the global victory over polio.
Koike, Satoshi; Nagata, Noriyo
Transgenic mice (tg mice) that express the human poliovirus receptor (PVR), CD155, are susceptible to poliovirus and develop a neurological disease that resembles human poliomyelitis. Assessment of the neurovirulence levels of poliovirus strains, including mutant viruses produced by reverse genetics, circulating vaccine-derived poliovirus, and vaccine candidates, is useful for basic research of poliovirus pathogenicity, the surveillance of circulating polioviruses, and the quality control of oral live poliovirus vaccines, and does not require the use of monkeys. Furthermore, PVR-tg mice are useful for studying poliovirus tissue tropism and host immune responses. PVR-tg mice can be bred with mice deficient in the genes involved in viral pathogenicity. This report describes the methods used to analyze the pathogenicity and immune responses of poliovirus using the PVR-tg mouse model.
Singh, Shirene M; Alkie, Tamiru N; Abdelaziz, Khaled Taha; Hodgins, Douglas C; Novy, Anastasia; Nagy, Éva; Sharif, Shayan
Avian influenza virus (AIV), a mucosal pathogen, gains entry into host chickens through respiratory and gastrointestinal routes. Most commercial AIV vaccines for poultry consist of inactivated, whole virus with adjuvant, delivered by parenteral administration. Recent advances in vaccine development have led to the application of nanoparticle emulsion delivery systems, such as poly (d,l-lactic-co-glycolic acid) (PLGA) nanoparticles to enhance antigen-specific immune responses. In chickens, the Toll-like receptor 21 ligand, CpG oligodeoxynucleotides (ODNs), have been demonstrated to be immunostimulatory. The objective of this study was to compare the adjuvant potential of CpG ODN 2007 encapsulated in PLGA nanoparticles with nonencapsulated CpG ODN 2007 when combined with a formalin-inactivated H9N2 virus, through intramuscular and aerosol delivery routes. Chickens were vaccinated at days 7 and 21 posthatch for the intramuscular route and at days 7, 21, and 35 for the aerosol route. Antibody-mediated responses were evaluated weekly in sera and lacrimal secretions in specific pathogen-free chickens. The results indicate that nonencapsulated CpG ODN 2007 in inactivated AIV vaccines administered by the intramuscular route generated higher antibody responses compared to the encapsulated CpG ODN 2007 formulation by the same route. Additionally, encapsulated CpG ODN 2007 in AIV vaccines administered by the aerosol route elicited higher mucosal responses compared to nonencapsulated CpG ODN 2007. Future studies may be aimed at evaluating protective immune responses induced with PLGA encapsulation of AIV and adjuvants.
Bowen, Richard A; Bosco-Lauth, Angela; Syvrud, Kevin; Thomas, Anne; Meinert, Todd R; Ludlow, Deborah R; Cook, Corey; Salt, Jeremy; Ons, Ellen
Over the last years West Nile virus (WNV) lineage 2 has spread from the African to the European continent. This study was conducted to demonstrate efficacy of an inactivated, lineage 1-based, WNV vaccine (Equip WNV) against intrathecal challenge of horses with a recent isolate of lineage 2 WNV. Twenty horses, sero-negative for WNV, were enrolled and were randomly allocated to one of two treatment groups: an unvaccinated control group (T01, n=10) and a group administered with Equip WNV (T02, n=10). Horses were vaccinated at Day 0 and 21 and were challenged at day 42 with WNV lineage 2, Nea Santa/Greece/2010. Personnel performing clinical observations were blinded to treatment allocation. Sixty percent of the controls had to be euthanized after challenge compared to none of the vaccinates. A significantly lower percentage of the vaccinated animals showed clinical disease (two different clinical observations present on the same day) on six different days of study and the percentage of days with clinical disease was significantly lower in the vaccinated group. A total of 80% of the non-vaccinated horses showed viremia while only one vaccinated animal was positive by virus isolation on a single occasion. Vaccinated animals started to develop antibodies against WNV lineage 2 from day 14 (2 weeks after the first vaccination) and at day 42 (the time of onset of immunity) they had all developed a strong antibody response. Histopathology scores for all unvaccinated animals ranged from mild to very severe in each of the tissues examined (cervical spinal cord, medulla and pons), whereas in vaccinated horses 8 of 10 animals had no lesions and 2 had minimal lesions in one tissue. In conclusion, Equip WNV significantly reduced the number of viremic horses, the duration and severity of clinical signs of disease and mortality following challenge with lineage 2 WNV. Copyright © 2014 Elsevier Ltd. All rights reserved.
Murugappan, Senthil; Patil, Harshad P; Frijlink, Henderik W; Huckriede, Anke; Hinrichs, Wouter L J
The best approach to control the spread of influenza virus during a pandemic is vaccination. Yet, an appropriate vaccine is not available early in the pandemic since vaccine production is time consuming. For influenza strains with a high pandemic potential like H5N1, stockpiling of vaccines has been
... and Teen Vaccine Resources Related Links Vaccines & Immunizations Polio and the Vaccine (Shot) to Prevent It Language: ... recommend all children get the vaccine. What is polio? Polio (or poliomyelitis) is a disease caused by ...
To avoid the risk of vaccine-associated paralytic poliomyelitis (VAPP) and polio outbreaks due to circulating vaccine-derived polioviruses, an inactivated poliovirus vaccine (IPV) was introduced for routine immunization in a number of countries with a low risk of polio outbreaks. Currently, production and marketing of a standalone conventional IPV and two diphtheria-pertussis-tetanus-IPV (Sabin-derived IPV; sIPV) products have been submitted, and it is expected that the IPV products will be introduced in Japan in the autumn of 2012. At the same time, a decline in the OPV immunization rate became apparent in Japan due to serious public concerns about a remaining risk of VAPP and introduction of IPV in the near future. Therefore, the recent development of polio immunity gaps should be carefully monitored, and surveillance of suspected polio cases and laboratory diagnosis of polioviruses have to be intensified for the transition period from OPV to IPV in Japan. The development of sIPV is one of the most realistic options to introduce affordable IPV to developing countries. In this regard, further clinical studies on its efficacy, safety, and interchangeability of sIPV will be needed after the introduction of the sIPV products, which will be licensed in Japan for the first time in the world.
Carman, S; Povey, C
Four experimental vaccine preparations comprising a strain of mink enteritis virus inactivated by either formalin or beta-propiolactone, and either adjuvanted or nonadjuvanted, failed to stimulate a consistent serum antibody response in 20 vaccinated dogs and failed to protect all but one of these dogs against oral challenge with canine parvovirus-2.
Full Text Available This study evaluates the effects of Sargassum pallidum polysaccharides (SPP on the immune responses in a chicken model. The adjuvanticity of Sargassum pallidum polysaccharides in Newcastle disease (ND, infectious bronchitis (IB and avian influenza (AI was investigated by examining the antibody titers and lymphocyte proliferation following immunization in chickens. The chickens were administrated combined ND, IB and AI inactivated vaccines containing SPP at 10, 30 and 50 mg/mL, using an oil adjuvant vaccine as a control. The ND, IB and AI antibody titers and the lymphocyte proliferation were enhanced at 30 mg/mL SPP. In conclusion, an appropriate dose of SPP may be a safe and efficacious immune stimulator candidate that is suitable for vaccines to produce early and persistent prophylaxis.
Katz, Mark A; Lebo, Emmaculate; Emukule, Gideon O; Otieno, Nancy; Caselton, Deborah L; Bigogo, Godfrey; Njuguna, Henry; Muthoka, Philip M; Waiboci, Lilian W; Widdowson, Marc-Alain; Xu, Xiyan; Njenga, Moses K; Mott, Joshua A; Breiman, Robert F
In Africa, recent surveillance has demonstrated a high burden of influenza, but influenza vaccine is rarely used. In Kenya, a country with a tropical climate, influenza has been shown to circulate year-round, like in other tropical countries. During 3 months in 2010 and 2011 and 2 months in 2012, the Kenya Medical Research Institute/Centers for Disease Control and Prevention-Kenya offered free injectable trivalent inactivated influenza vaccine to children 6 months to 10 years old in 2 resource-poor communities in Kenya-Kibera and Lwak (total population ~50,000). We conducted a case-control study to evaluate vaccine effectiveness (VE) in preventing laboratory-confirmed influenza associated with influenza-like illness and acute lower respiratory illness. Of the approximately 18,000 eligible children, 41%, 48% and 51% received at least 1 vaccine in 2010, 2011 and 2012, respectively; 30%, 36% and 38% were fully vaccinated. VE among fully vaccinated children was 57% [95% confidence interval (CI): 29% to 74%] during a 6-month follow-up period, 39% (95% CI: 17% to 56%) during a 9-month follow-up period and 48% (95% CI: 32% to 61%) during a 12-month follow-up period. For the 12-month follow-up period, VE was statistically significant in children Kenya, parents of nearly half of the eligible children <10 years old chose to get their children vaccinated with a free influenza vaccine. During a 12-month follow-up period, the vaccine was moderately effective in preventing medically attended influenza-associated respiratory illness.
Full Text Available Vaccination against tuberculosis (TB is prohibited in cattle or other species subjected to specific TB eradication campaigns, due to the interference that it may cause with the official diagnostic tests. However, immunization with a heat-inactivated (HI Mycobacterium bovis vaccine via the oral route has been suggested to overcome this issue. In this study, the main goal was to assess the interference of the HI vaccine by different routes of administration using a previous vaccination and re-vaccination (boosting protocol. TB-free kid goats were divided into three groups: oral (n = 16, intramuscular (IM; n = 16, and control (n = 16. Results showed that there was a significant difference in the percentage of animals positive to the single intradermal test (SIT and blood based interferon-gamma release assay (IGRA caused by vaccination when performed in the IM group compared to the oral group (p < 0.001. Nevertheless, no positivity to the SIT or IGRA test was observed in orally vaccinated goats regardless of the different interpretation criteria applied. None of the groups presented positive antibody titers using an in-house ELISA and samples collected 2 months after the boost. These results suggest the potential usefulness of the HI vaccine by the oral route in goats to minimize the interference on diagnostic tests (skin and IGRA tests and reducing the necessity of defined antigens to replace the traditional purified protein derivatives for diagnosis. Finally, the results pave the way to future efficacy studies in goats using different routes of HI vaccination.
Gordon, David L; Sajkov, Dimitar; Honda-Okubo, Yoshikazu; Wilks, Samuel H; Aban, Malet; Barr, Ian G; Petrovsky, Nikolai
Influenza vaccines are usually non-adjuvanted but addition of adjuvant may improve immunogenicity and permit dose-sparing, critical for vaccine supply in the event of an influenza pandemic. The aim of this first-in-man study was to determine the effect of delta inulin adjuvant on the safety and immunogenicity of a reduced dose seasonal influenza vaccine. Healthy male and female adults aged 18-65years were recruited to participate in a randomized controlled study to compare the safety, tolerability and immunogenicity of a reduced-dose 2007 Southern Hemisphere trivalent inactivated influenza vaccine formulated with Advax™ delta inulin adjuvant (LTIV+Adj) when compared to a full-dose of the standard TIV vaccine which does not contain an adjuvant. LTIV+Adj provided equivalent immunogenicity to standard TIV vaccine as assessed by hemagglutination inhibition (HI) assays against each vaccine strain as well as against a number of heterosubtypic strains. HI responses were sustained at 3months post-immunisation in both groups. Antibody landscapes against a large panel of H3N2 influenza viruses showed distinct age effects whereby subjects over 40years old had a bimodal baseline HI distribution pattern, with the highest HI titers against the very oldest H3N2 isolates and with a second HI peak against influenza isolates from the last 5-10years. By contrast, subjects >40years had a unimodal baseline HI distribution with peak recognition of H3N2 isolates from approximately 20years ago. The reduced dose TIV vaccine containing Advax adjuvant was well tolerated and no safety issues were identified. Hence, delta inulin may be a useful adjuvant for use in seasonal or pandemic influenza vaccines. Australia New Zealand Clinical Trial Registry: ACTRN12607000599471. Copyright © 2016 Elsevier Ltd. All rights reserved.
Sato, Y; Shiosaki, K; Goto, Y; Sonoda, K; Kino, Y
Antibody responses of Macaca fascicularis against a new tetravalent vaccine composed of diphtheria toxoid, tetanus toxoid, acellular pertussis antigens, and inactivated poliovirus derived from Sabin strains (sIPV) was investigated to predict an optimal dose of sIPV in a new tetravalent vaccine (DTaP-sIPV) prior to conducting a dose-defined clinical study. Monkeys were inoculated with DTaP-sIPVs containing three different antigen units of sIPVs: Vaccine A (types 1:2:3 = 3:100:100 DU), Vaccine B (types 1:2:3 = 1.5:50:50 DU), and Vaccine C (types 1:2:3 = 0.75:25:25 DU). There was no difference in the average titers of neutralizing antibody against the attenuated or virulent polioviruses between Vaccines A and B. The average neutralizing antibody titers of Vaccine C tended to be lower than those of Vaccines A and B. The sIPV antigens did not affect the anti-diphtheria or anti-tetanus antibody titers of DTaP-sIPV. Furthermore, the average neutralizing antibody titers of Vaccine A against the attenuated and virulent polioviruses were comparable between M. fascicularis and humans. These results suggest that M. fascicularis may be a useful animal model for predicting the antibody responses to sIPVs in humans, and that it may be likely to reduce the amount of sIPVs contained in DTaP-sIPVs, even for humans. Copyright © 2013 The International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.
Resik, Sonia; Tejeda, Alina; Fonseca, Magilé; Alemañi, Nilda; Diaz, Manuel; Martinez, Yenisleidys; Garcia, Gloria; Okayasu, Hiromasa; Burton, Anthony; Bakker, Wilfried A M; Verdijk, Pauline; Sutter, Roland W
To ensure that developing countries have the option to produce inactivated poliovirus vaccine (IPV), the Global Polio Eradication Initiative has promoted the development of an IPV using Sabin poliovirus strains (Sabin IPV). This trial assessed the reactogenicity and immunogenicity of Sabin IPV and adjuvanted Sabin IPV in healthy adults in Cuba. This is a randomized, controlled phase I trial, enrolling 60 healthy (previously vaccinated) male human volunteers, aged 19-23 years to receive one dose of either Sabin IPV (20:32:64 DU/dose), adjuvanted Sabin IPV (10:16:32 DU/dose), or conventional Salk IPV (40:8:32 DU/dose). The primary endpoint for reactogenicity relied on monitoring of adverse events. The secondary endpoint measured boosting immune responses (i.e. seroconversion or 4-fold rise) of poliovirus antibody, assessed by neutralization assays. Sixty subjects fulfilled the study requirements. No serious adverse events reported were attributed to trial interventions during the 6-month follow-up period. Twenty-eight days after vaccination, boosting immune responses against poliovirus types 1-3 were between 90% and 100% in all vaccination groups. There was a more than 6-fold increase in median antibody titers between pre- and post-vaccination titers in all vaccination groups. Both Sabin IPV and adjuvanted Sabin IPV were well tolerated and immunogenic against all poliovirus serotypes. This result suggests that the aluminum adjuvant may allow a 50% (or higher) dose reduction. Copyright © 2014. Published by Elsevier Ltd.
Dhakal, Santosh; Renu, Sankar; Ghimire, Shristi; Shaan Lakshmanappa, Yashavanth; Hogshead, Bradley T; Feliciano-Ruiz, Ninoshkaly; Lu, Fangjia; HogenEsch, Harm; Krakowka, Steven; Lee, Chang Won; Renukaradhya, Gourapura J
Annually, swine influenza A virus (SwIAV) causes severe economic loss to swine industry. Currently used inactivated SwIAV vaccines administered by intramuscular injection provide homologous protection, but limited heterologous protection against constantly evolving field viruses, attributable to the induction of inadequate levels of mucosal IgA and cellular immune responses in the respiratory tract. A novel vaccine delivery platform using mucoadhesive chitosan nanoparticles (CNPs) administered through intranasal (IN) route has the potential to elicit strong mucosal and systemic immune responses in pigs. In this study, we evaluated the immune responses and cross-protective efficacy of IN chitosan encapsulated inactivated SwIAV vaccine in pigs. Killed SwIAV H1N2 (δ-lineage) antigens (KAg) were encapsulated in chitosan polymer-based nanoparticles (CNPs-KAg). The candidate vaccine was administered twice IN as mist to nursery pigs. Vaccinates and controls were then challenged with a zoonotic and virulent heterologous SwIAV H1N1 (γ-lineage). Pigs vaccinated with CNPs-KAg exhibited an enhanced IgG serum antibody and mucosal secretory IgA antibody responses in nasal swabs, bronchoalveolar lavage (BAL) fluids, and lung lysates that were reactive against homologous (H1N2), heterologous (H1N1), and heterosubtypic (H3N2) influenza A virus strains. Prior to challenge, an increased frequency of cytotoxic T lymphocytes, antigen-specific lymphocyte proliferation, and recall IFN-γ secretion by restimulated peripheral blood mononuclear cells in CNPs-KAg compared to control KAg vaccinates were observed. In CNPs-KAg vaccinated pigs challenged with heterologous virus reduced severity of macroscopic and microscopic influenza-associated pulmonary lesions were observed. Importantly, the infectious SwIAV titers in nasal swabs [days post-challenge (DPC) 4] and BAL fluid (DPC 6) were significantly ( p influenza nanovaccine may be an ideal candidate vaccine for use in pigs, and pig is a
Okada, Kenji; Miyazaki, Chiaki; Kino, Yoichiro; Ozaki, Takao; Hirose, Mizuo; Ueda, Kohji
Phase II and III clinical studies were conducted to evaluate immunogenicity and safety of a novel DTaP-IPV vaccine consisting of Sabin inactivated poliovirus vaccine (sIPV) and diphtheria-tetanus-acellular pertussis vaccine (DTaP). A Phase II study was conducted in 104 healthy infants using Formulation H of the DTaP-sIPV vaccine containing high-dose sIPV (3, 100, and 100 D-antigen units for types 1, 2, and 3, respectively), and Formulations M and L, containing half and one-fourth of the sIPV in Formulation H, respectively. Each formulation was administered 3 times for primary immunization and once for booster immunization. A Phase III study was conducted in 342 healthy infants who received either Formulation M + oral polio vaccine (OPV) placebo or DTaP + OPV. The OPV or OPV placebo was orally administered twice between primary and booster immunizations. Formulation M was selected as the optimum dose. In the Phase III study, the seropositive rate was 100% for all Sabin strains after primary immunization, and the neutralizing antibody titer after booster immunization was higher than in the control group (DTaP + OPV). All adverse reactions were clinically acceptable. DTaP-sIPV was shown to be a safe and immunogenic vaccine. JapicCTI-121902 for Phase II study, JapicCTI-101075 for Phase III study (http://www.clinicaltrials.jp/user/cte_main.jsp).
Full Text Available Foot-and-mouth disease (FMD is a severely contagious viral disease that mainly affects cloven-hoofed livestock and wildlife. This study quantifies the cytokines mRNA expression of vaccinated guinea pigs with FMD type O inactivated vaccine. Blood samples were collected from eight guinea pigs at 7 and 28 days after the first vaccination. Extracted mRNAs were reverse-transcribed into cDNA and analyzed for quantiﬁcation of IFN-γ, TNF-α and IL-10 expression using relative real-time PCR assay. Our results showed that all of the genes were upregulated. The expression of TNF-α and IL-10 genes significantly increased (P<0.05 in day 28th in comparison to the day 7th post the first vaccination. It can be concluded that the vaccine induced immune responses by increasing expression of the cytokines. Therefore, effects of DNA vaccines on immune system also may be evaluated using these genes.
Wang, Jichun; Guo, Rongli; Qiao, Yongfeng; Xu, Mengwei; Wang, Zhisheng; Liu, Yamei; Gu, Yiqi; Liu, Chang; Hou, Jibo
Since the end of 2011 an outbreak of pseudorabies affected Chinese pig herds that had been vaccinated with the commercial vaccine made of Bartha K61 strain. It is now clear that the outbreak was caused by an emergent PRV variant. Even though vaccines made of PRV Bartha K61 strain can confer certain cross protection against PRV variants based on experimental data, less than optimal clinical protection and virus shedding reduction were observed, making the control or eradication of this disease difficult. An infectious clone of PRV AH02LA strain was constructed to generate a gE deletion mutant PRV(LA-A B ) strain. PRV(LA-A B ) strain can reach a titer of 10 8.43 TCID 50 /mL (50% tissue culture infectious dose) on BHK-21 cells. To evaluate the efficiency of the inactivated vaccine made of PRV(LA-A B ) strain, thirty 3-week-old PRV-negative piglets were divided randomly into six groups for vaccination and challenge test. All five piglets in the challenge control showed typical clinical symptoms of pseudorabies post challenge. Sneezing and nasal discharge were observed in four and three piglets in groups C(vaccinated with inactivated PRV Bartha K61 strain vaccine) and D(vaccinated with live PRV Bartha K61 strain vaccine) respectively. In contrast, piglets in both groups A(vaccinated with inactivated PRV LA-AB strain vaccine) and B(vaccinated with inactivated PRV LA-A B strain vaccine with adjuvant) presented mild or no clinical symptoms. Moreover, viral titers detected via nasal swabs were approximately 100 times lower in group B than in the challenge control, and the duration of virus shedding (3-4 days) was shorter than in either the challenge control (5-10 days) or groups C and D (5-6 days). The infectious clone constructed in this study harbors the whole genome of the PRV variant AH02LA strain. The gE deletion mutant PRV(LA-A B )strain generated from PRV AH02LA strain can reach a high titer on BHK-21 cells. An inactivated vaccine of PRV LA-A B provides clinical
Sun, Yuelian; Christensen, Jakob; Hviid, Anders; Li, Jiong; Vedsted, Peter; Olsen, Jørn; Vestergaard, Mogens
Vaccination with whole-cell pertussis vaccine carries an increased risk of febrile seizures, but whether this risk applies to the acellular pertussis vaccine is not known. In Denmark, acellular pertussis vaccine has been included in the combined diphtheria-tetanus toxoids-acellular pertussis-inactivated poliovirus-Haemophilus influenzae type b (DTaP-IPV-Hib) vaccine since September 2002. To estimate the risk of febrile seizures and epilepsy after DTaP-IPV-Hib vaccination given at 3, 5, and 12 months. A population-based cohort study of 378,834 children who were born in Denmark between January 1, 2003, and December 31, 2008, and followed up through December 31, 2009; and a self-controlled case series (SCCS) study based on children with febrile seizures during follow-up of the cohort. Hazard ratio (HR) of febrile seizures within 0 to 7 days (0, 1-3, and 4-7 days) after each vaccination and HR of epilepsy after first vaccination in the cohort study. Relative incidence of febrile seizures within 0 to 7 days (0, 1-3, and 4-7 days) after each vaccination in the SCCS study. A total of 7811 children were diagnosed with febrile seizures before 18 months, of whom 17 were diagnosed within 0 to 7 days after the first (incidence rate, 0.8 per 100,000 person-days), 32 children after the second (1.3 per 100,000 person-days), and 201 children after the third (8.5 per 100,000 person-days) vaccinations. Overall, children did not have higher risks of febrile seizures during the 0 to 7 days after the 3 vaccinations vs a reference cohort of children who were not within 0 to 7 days of vaccination. However, a higher risk of febrile seizures was found on the day of the first (HR, 6.02; 95% CI, 2.86-12.65) and on the day of the second (HR, 3.94; 95% CI, 2.18-7.10), but not on the day of the third vaccination (HR, 1.07; 95% CI, 0.73-1.57) vs the reference cohort. On the day of vaccination, 9 children were diagnosed with febrile seizures after the first (5.5 per 100,000 person-days), 12
Full Text Available Efficacy of an inactivated quadrivalent vaccine containing infectious bovine rhinotracheitis (IBR virus, parainfluenza type 3 (PI3 virus, bovine virus diarrhoea virus (BVDV and bovine respiratory syncytial virus (BRSV was assessed in naive bovine calves to evaluate short-term (4-18 weeks and long-term (24-38 weeks protection following the basic intramuscular vaccination regime of 2 inoculations a month apart. Vaccination was staggered between the long-term and the short-term groups by about 5 months so that both groups, along with a matched group of 6 unvaccinated (control calves, could be challenged at the same time. Sequential challenges at intervals of 3-8 weeks were done in the order: IBR virus (intranasally, IN, PI3 virus (IN and intratracheally, IT, pestiviruses (IN and BRSV (IN and IT. The IBR virus challenge produced febrile rhinotracheitis (FRT in control calves but both the severity and the duration of FRT was significantly reduced in both vaccinated groups. The amount and the duration of IBR virus shed by the vaccinated groups was significantly reduced compared to the control group. Although PI3 virus, pooled pestivirus and BRSV challenges did not result in a noteworthy disease, challenge virus shedding (amount and duration from the upper (all 3 viruses and the lower (BRSV respiratory tracts was significantly reduced in vaccinated groups. After pestivirus challenge, sera and leukocytes from all control calves were infectious for 6-9 days whereas virus was recovered only from leukocytes in vaccinated calves and only for 1.6-2.7 days. Thus a standard course of the quadrivalent vaccine afforded a significant protection against IBR virus, PI3 virus, BVDV and BRSV for at least 6 months.
Sanders, Barbara P; Edo-Matas, Diana; Papic, Natasa; Schuitemaker, Hanneke; Custers, Jerome H H V
Safety of vaccines can be compromised by contamination with adventitious agents. One potential source of adventitious agents is a vaccine seed, typically derived from historic clinical isolates with poorly defined origins. Here we generated synthetic poliovirus seeds derived from chemically synthesized DNA plasmids encoding the sequence of wild-type poliovirus strains used in marketed inactivated poliovirus vaccines. The synthetic strains were phenotypically identical to wild-type polioviruses as shown by equivalent infectious titers in culture supernatant and antigenic content, even when infection cultures are scaled up to 10-25L bioreactors. Moreover, the synthetic seeds were genetically stable upon extended passaging on the PER.C6 cell culture platform. Use of synthetic seeds produced on the serum-free PER.C6 cell platform ensures a perfectly documented seed history and maximum control over starting materials. It provides an opportunity to maximize vaccine safety which increases the prospect of a vaccine end product that is free from adventitious agents. Copyright © 2015 Elsevier Ltd. All rights reserved.
Noack, K.; Tischner, H.; Pohl, W.D.; Braeuniger, S.; Nordheim, W.
NMRI mice were immunized orally twice within 10 days with an influenza vaccine inactivated by gamma radiation. The immunization with a relatively low dosis led to the occurence of low specific antibody titer in the lung lavage fluid up to 6th month. Despite of the low titer, immunized mice were protected against aerogenic infection for about 6 months. Protection was demonstrated in comparison to non-immunized mice by a limited increase of cells in bronchoalveolar lavage, low virus titer in the lung and survival of most animals after a lethal aerosol challenge with the live virus. (author)
Collin, Emily A; Anbalagan, Srivishnupriya; Okda, Faten; Batman, Ron; Nelson, Eric; Hause, Ben M
Porcine epidemic diarrhea virus (PEDV), a highly pathogenic and transmissible virus in swine, was first detected in the U.S. in May, 2013, and has caused tremendous losses to the swine industry. Due to the difficulty in isolating and growing this virus in cell culture, few vaccine studies using cell culture propagated PEDV have been performed on U.S. strains in pigs. Therefore, the objective of this study was to evaluate the humoral immune response to the selected inactivated PEDV vaccine candidate in a dose-titration manner. PEDV was isolated from a pig with diarrhea and complete genome sequencing found >99% nucleotide identity to other U.S. PEDV. Inactivated adjuvanted monovalent vaccines were administered intramuscularly to five week old pigs in a dose titration experimental design, ranging from 6.0-8.0 log10 tissue culture infective dose (TCID50/mL), to evaluate immunogenicity using a fluorescent foci neutralization assay (FFN), fluorescent microsphere immunoassay (FMIA), and enzyme-linked immunosorbent assay (ELISA) on sera. Pigs vaccinated with 8.0 log10 TCID50/mL inactivated virus showed significantly higher FFN titers as well as FMIA and ELISA values than 6.0 log10 TCID50/mL vaccinates and the negative controls. These results demonstrate the immunogenicity of a PEDV inactivated viral vaccine with a U.S. strain via dose-titration. A future vaccination-challenge study would illustrate the efficacy of an inactivated vaccine and help evaluate protective FFN titers and ELISA and FMIA responses.
Schulze, L S-Ch; Borchardt, S; Ouellet, V; Heuwieser, W
Q fever is a zoonotic disease caused by Coxiella burnetii. The pathogen is prevalent in ruminants (goats, sheep, cows), which are the main sources of human infection. In the cattle industry around the world, animal (15 to 20%) and herd (38 to 72%) level prevalences of C. burnetii are high. Vaccination of ruminants against Q fever is considered important to prevent spreading of the disease and risk of infection in humans. However, published information on side effects of the Q fever vaccination under field conditions is limited for cows. The objective of this study was to investigate the effect of the phase I C. burnetii inactivated vaccine Coxevac on body temperature and milk yield in dairy cows. In 2 experiments, a total of 508 cows were randomly divided into 2 groups to determine the effect of first vaccination on body temperature and milk yield. The C. burnetii serostatus of all cows was tested before vaccination with an indirect ELISA. The first experiment took place in the teaching and research barn of the Clinic of Animal Reproduction at the Freie Universität Berlin. Temperature was measured vaginally in 10 cows in a crossover design. The second experiment was conducted on a commercial dairy farm. Milk yield of 498 cows was measured 1 wk before and 1 wk after vaccination. In a subset of 41 cows, temperature was measured rectally. In both experiments, body temperature increased significantly after vaccination (1.0 ± 0.9°C and 0.7 ± 0.8°C). A significant difference was also found in body temperature between vaccinated and control cows. Thirty percent of the vaccinated animals in experiment 1 showed reversible swelling at the injection site as a reaction to the vaccination. The results indicate that vaccination against Q fever causes a transient increase of body temperature that peaks in the first 12 to 24h and declines after that. In experiment 2, vaccinated cows (26.8 ± 0.39 kg/d) produced significantly less milk than did control cows (28.2 ± 0.44 kg
Full Text Available The eye route has been evaluated as an efficient vaccine delivery routes. However, in order to induce sufficient antibody production with inactivated vaccine, testing of the safety and efficacy of the use of inactivated antigen plus adjuvant is needed. Here, we assessed various types of adjuvants in eyedrop as an anti-influenza serum and mucosal Ab production-enhancer in BALB/c mice. Among the adjuvants, poly (I:C showed as much enhancement in antigen-specific serum IgG and mucosal IgA antibody production as cholera toxin (CT after vaccinations with trivalent hemagglutinin-subunits or split H1N1 vaccine antigen in mice. Vaccination with split H1N1 eyedrop vaccine antigen plus poly(I:C showed a similar or slightly lower efficacy in inducing antibody production than intranasal vaccination; the eyedrop vaccine-induced immunity was enough to protect mice from lethal homologous influenza A/California/04/09 (H1N1 virus challenge. Additionally, ocular inoculation with poly(I:C plus vaccine antigen generated no signs of inflammation within 24 hours: no increases in the mRNA expression levels of inflammatory cytokines nor in the infiltration of mononuclear cells to administration sites. In contrast, CT administration induced increased expression of IL-6 cytokine mRNA and mononuclear cell infiltration in the conjunctiva within 24 hours of vaccination. Moreover, inoculated visualizing materials by eyedrop did not contaminate the surface of the olfactory bulb in mice; meanwhile, intranasally administered materials defiled the surface of the brain. On the basis of these findings, we propose that the use of eyedrop inactivated influenza vaccine plus poly(I:C is a safe and effective mucosal vaccine strategy for inducing protective anti-influenza immunity.
Sanders, Barbara P.; Edo-Matas, Diana; Custers, Jerome H. H. V.; Koldijk, Martin H.; Klaren, Vincent; Turk, Marije; Luitjens, Alfred; Bakker, Wilfried A. M.; Uytdehaag, Fons; Goudsmit, Jaap; Lewis, John A.; Schuitemaker, Hanneke
There are two highly efficacious poliovirus vaccines: Sabin's live-attenuated oral polio vaccine (OPV) and Salk's inactivated polio vaccine (IPV). OPV can be made at low costs per dose and is easily administrated. However, the major drawback is the frequent reversion of the OPV vaccine strains to
Yang, Chunting; Shi, Huiying; Zhou, Jun; Liang, Yanwen; Xu, Honglin
Poliovirus transmission is controlled globally through world-wide use of a live attenuated oral polio vaccine (OPV). However, the imminence of global poliovirus eradication calls for a switch to the inactivated polio vaccine (IPV). Given the limited manufacturing capacity and high cost of IPV, this switch is unlikely in most developing and undeveloped countries. Adjuvantation is an effective strategy for antigen sparing. In this study, we evaluated the adjuvanticity of CpG oligodeoxynucleotides (CpG-ODN) for an experimental IPV produced from Sabin strains of poliovirus. Our results showed that CpG-ODN, alone or in combination with alum, can significantly enhance both the humoral and cellular immune responses to IPV in mice, and, consequently, the antigen dose could be reduced substantially. Therefore, our study suggests that the global use of IPV could be facilitated by using CpG-ODN or other feasible adjuvants.
Liu, Yan; Wang, Jun; Liu, Shijun; Du, Jian; Wang, Liang; Gu, Wenwen; Xu, Yuyang; Zuo, Shuyan; Xu, Erping; An, Zhijie
China's Expanded Program on Immunization (EPI) has provided 4 doses of oral poliovirus vaccine (OPV) since the 1970s. Inactivated poliovirus vaccine (IPV) became available in 2010 in Hangzhou as a private-sector, parent-chosen alternative to OPV. In 2015, WHO recommended that countries with all-OPV vaccination schedules introduce at least one dose of IPV, to mitigate risk associated with the withdrawal of type 2 OPV. We analyzed polio vaccine coverage and utilization in Hangzhou to determine patterns of IPV use and the occurrence of vaccine-associated paralytic polio (VAPP) in the various patterns identified. Children born between 2010 and 2014 and registered in Hangzhou's Immunization Information System (HZIIS) were included. VAPP cases were detected through the acute flaccid paralysis surveillance system. We used descriptive epidemiological methods to determine IPV and OPV usage patterns and VAPP occurrence. HZIIS data from 566,894 children were analyzed. Coverage levels of polio vaccine were greater than 92% for each birth cohort. Percentages of children using OPV-only, IPV-only, and IPV/OPV sequential schedules were 70.57%, 27.01% and 2.41%, respectively. IPV-only schedule utilization increased by birth cohort regardless of geographical area or whether the child was locally-born. The highest use of an all-IPV schedule (79.85%) was among urban, locally-born children in the 2014 birth cohort. Five VAPP cases were identified during the study years; all cases occurred following the first polio vaccine dose, which was always OPV for the cases. Type 2 vaccine virus was isolated from 2 VAPP cases, and type 2 and type 3 vaccine virus was isolated from one VAPP case. The incidence of VAPP in the 2010-2014 birth cohorts was 3.76 per 1million doses of OPV. Children in Hangzhou had high polio vaccination coverage. IPV-only schedule use increased by year, and was highest in urban areas among locally-born children. All cases of VAPP were associated with the first dose of OPV
Domingues, Carla Magda Allan S.; de Fátima Pereira, Sirlene; Marreiros, Ana Carolina Cunha; Menezes, Nair; Flannery, Brendan
In August 2012, the Brazilian Ministry of Health introduced inactivated polio vaccine (IPV) as part of sequential polio vaccination schedule for all infants beginning their primary vaccination series. The revised childhood immunization schedule included 2 doses of IPV at 2 and 4 months of age followed by 2 doses of oral polio vaccine (OPV) at 6 and 15 months of age. One annual national polio immunization day was maintained to provide OPV to all children aged 6 to 59 months. The decision to introduce IPV was based on preventing rare cases of vaccine-associated paralytic polio, financially sustaining IPV introduction, ensuring equitable access to IPV, and preparing for future OPV cessation following global eradication. Introducing IPV during a national multivaccination campaign led to rapid uptake, despite challenges with local vaccine supply due to high wastage rates. Continuous monitoring is required to achieve high coverage with the sequential polio vaccine schedule. PMID:25316829
Someya, Yuichi; Ami, Yasushi; Takai-Todaka, Reiko; Fujimoto, Akira; Haga, Kei; Murakami, Kosuke; Fujii, Yoshiki; Shirato, Haruko; Oka, Tomoichiro; Shimoike, Takashi; Katayama, Kazuhiko; Wakita, Takaji
Slc:Wistar rats have been the only strain used in Japan for purpose of evaluating a national reference vaccine for the Sabin-derived inactivated polio vaccine (sIPV) and the immunogenicity of sIPV-containing products. However, following the discovery that the Slc:Wistar strain was genetically related to the Fischer 344 strain, other "real" Wistar strains, such as Crlj:WI, that are available worldwide were tested in terms of their usefulness in evaluating the immunogenicity of the past and current lots of a national reference vaccine. The response of the Crlj:WI rats against the serotype 1 of sIPV was comparable to that of the Slc:Wistar rats, while the Crlj:WI rats exhibited a higher level of response against the serotypes 2 and 3. The immunogenic potency units of a national reference vaccine determined using the Slc:Wistar rats were reproduced on tests using the Crlj:WI rats. These results indicate that a titer of the neutralizing antibody obtained in response to a given dose of sIPV cannot be directly compared between these two rat strains, but that, more importantly, the potency units are almost equivalent for the two rat strains. Copyright © 2018 International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.
Wahjuhono, Gendro; Revolusiana; Widhiastuti, Dyah; Sundoro, Julitasari; Mardani, Tri; Ratih, Woro Umi; Sutomo, Retno; Safitri, Ida; Sampurno, Ondri Dwi; Rana, Bardan; Roivainen, Merja; Kahn, Anna-Lea; Mach, Ondrej; Pallansch, Mark A; Sutter, Roland W
Inactivated poliovirus vaccine (IPV) is rarely used in tropical developing countries. To generate additional scientific information, especially on the possible emergence of vaccine-derived polioviruses (VDPVs) in an IPV-only environment, we initiated an IPV introduction project in Yogyakarta, an Indonesian province. In this report, we present the coverage, immunity, and VDPV surveillance results. In Yogyakarta, we established environmental surveillance starting in 2004; and conducted routine immunization coverage and seroprevalence surveys before and after a September 2007 switch from oral poliovirus vaccine (OPV) to IPV, using standard coverage and serosurvey methods. Rates and types of polioviruses found in sewage samples were analyzed, and all poliovirus isolates after the switch were sequenced. Vaccination coverage (>95%) and immunity (approximately 100%) did not change substantially before and after the IPV switch. No VDPVs were detected. Before the switch, 58% of environmental samples contained Sabin poliovirus; starting 6 weeks after the switch, Sabin polioviruses were rarely isolated, and if they were, genetic sequencing suggested recent introductions. This project demonstrated that under almost ideal conditions (good hygiene, maintenance of universally high IPV coverage, and corresponding high immunity against polioviruses), no emergence and circulation of VDPV could be detected in a tropical developing country setting. © 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: firstname.lastname@example.org.
Tzivara, A; Kritas, S K; Bourriel, A R; Alexopoulos, C; Kyriakis, S C
The efficacy of an inactivated aqueous vaccine against Mycoplasma hyopneumoniae was evaluated at two M hyopneumoniae-infected farrow-to-finish commercial farms (A and B) in Greece. In a prospective, randomised double-blind study, two groups on each farm received intramuscular doses of either the vaccine or the adjuvant when they were one and four weeks of age. The pigs were observed daily for clinical signs of disease; morbidity and mortality were recorded; and bodyweight was recorded at intervals. At slaughter, the lungs of the animals were examined and the chest cavities were examined for signs of pleuritis. No adverse reactions to the treatments were observed in any of the pigs. On farm A the vaccinated pigs were on average 6 kg heavier at slaughter, and on farm B they were on average 4 kg heavier; on both farms the average daily gain of the pigs was greater than that of the unvaccinated pigs. The prevalence and severity of enzootic pneumonia in the affected lungs were significantly lower in the vaccinated than in the unvaccinated pigs.
Bertelsen, Mads F.; Klausen, Joan; Holm, Elisabeth
seroconverted, and 76% developed a titre >= 32. The geometric mean titre after vaccination was 137. A significant species variation in response was noted; penguins, pelicans, ducks, geese, herons, Guinea fowl, cranes, cockatiels, lovebirds, and barbets showed very poor response to vaccination, while very high...
Concomitant administration of diphtheria, tetanus, acellular pertussis and inactivated poliovirus vaccine derived from Sabin strains (DTaP-sIPV) with pentavalent rotavirus vaccine in Japanese infants.
Tanaka, Yoshiyuki; Yokokawa, Ruriko; Rong, Han Shi; Kishino, Hiroyuki; Stek, Jon E; Nelson, Margaret; Lawrence, Jody
Rotavirus is the leading cause of severe acute gastroenteritis in infants and young children. Most children are infected with rotavirus, and the health and economic burdens of rotavirus gastroenteritis on healthcare systems and families are considerable. In 2012 pentavalent rotavirus vaccine (RV5) and diphtheria, tetanus, acellular pertussis and inactivated poliovirus vaccine derived from Sabin strains (DTaP-sIPV) were licensed in Japan. We examined the immunogenicity and safety of DTaP-sIPV when administrated concomitantly with RV5 in Japanese infants. A total of 192 infants 6 to 11 weeks of age randomized to Group 1 (N = 96) received DTaP-sIPV and RV5 concomitantly, and Group 2 (N = 96) received DTaP-sIPV and RV5 separately. Antibody titer to diphtheria toxin, pertussis antigens (PT and FHA), tetanus toxin, and poliovirus type 1, 2, and 3 were measured at 4 to 6 weeks following 3-doses of DTaP-sIPV. Seroprotection rates for all components of DTaP-sIPV were 100% in both groups, and the geometric mean titers for DTaP-sIPV in Group 1 were comparable to Group 2. Incidence of systemic AEs (including diarrhea, vomiting, fever, and nasopharyngitis) were lower in Group 1 than in Group 2. All vaccine-related AEs were mild or moderate in intensity. There were no vaccine-related serious AEs, no deaths, and no cases of intussusception during the study. Concomitant administration of DTaP-sIPV and RV5 induced satisfactory immune responses to DTaP-sIPV and acceptable safety profile. The administration of DTaP-sIPV given concomitantly with RV5 is expected to facilitate compliance with the vaccination schedule and improve vaccine coverage in Japanese infants.
Patel, M; Carritt, K; Lane, J; Jayappa, H; Stahl, M; Bourgeois, M
Four vaccines for feline leukemia virus (FeLV) are available in the United States. This study's purpose was to compare the efficacy of Nobivac feline 2-FeLV (an inactivated, adjuvanted whole-virus vaccine) and PureVax recombinant FeLV (a live, canarypox virus-vectored vaccine) following FeLV challenge. Cats were vaccinated at 9 and 12 weeks with Nobivac feline 2-FeLV (group A, n = 11) or PureVax recombinant FeLV (group B, n = 10). Group C (n = 11) comprised unvaccinated controls. At 3 months postvaccination, cats were immunosuppressed and challenged with FeLV-A/61E. The outcomes measured were persistent antigenemia at 12 weeks postchallenge (PC) and proviral DNA and viral RNA at 3 to 9 weeks PC. Persistent antigenemia was observed in 0 of 11 cats in group A, 5 of 10 cats in group B, and 10 of 11 cats in group C. Group A was significantly protected compared to those in groups B (P 0.063). The preventable fraction was 100% for group A and 45% for group B. At 9 weeks PC, proviral DNA and viral RNA were detected 1 of 11 cats in group A, 6 of 10 cats in group B, and 9 of 11 cats in group C. Nucleic acid loads were significantly lower in group A than in group C (P feline 2-FeLV-vaccinated cats were fully protected against persistent antigenemia and had significantly smaller amounts of proviral DNA and plasma viral RNA loads than PureVax recombinant FeLV-vaccinated cats and unvaccinated controls. Copyright © 2015, Patel et al.
Full Text Available OBJETIVOS: Evaluar la relación costo-efectividad de la introducción de la vacuna inyectable contra la poliomielitis (VIP en Colombia con respecto al sistema actual basado en el empleo de la vacuna oral (VOP. MÉTODOS: Se diseñó un modelo de Markov basado en una cohorte hipotética de recién nacidos que recibiría la VIP o la VOP con un seguimiento de dos años y estimaciones mensuales del número de casos de poliomielitis paralítica asociada con la vacuna (PPAV. El análisis del costo se realizó desde la perspectiva del asegurador (costos a lo largo de la vida y la sociedad (casos de PPAV evitados y años de vida ajustados por discapacidad [AVAD] evitados. RESULTADOS: Entre 1988 y 1998 se aplicaron en Colombia 22,5 millones de dosis de la VOP y se detectaron nueve casos de PPAV, para una tasa de 4,0 ¥ 10-7 por dosis. Según el modelo, se podrían esperar entre 2 y 4 casos de PPAV en los dos años de seguimiento. El costo de tratar los casos de PPAV sería de US$ 302 008, con costos de vacunación con la VOP de US$ 737 037 y de US$ 5 527 777 con la VIP. La vacunación con la VIP permitiría evitar 64 AVAD con un costo de US$ 71 062 por AVAD evitado; evitar un caso de PPAV mediante la sustitución de la VOP por la VIP costaría entre US$ 1,8 millones y US$ 2,2 millones. CONCLUSIONES: La sustitución de la VOP por la VIP no es una medida efectiva en función del costo en Colombia, incluso si se sustituyera la vacuna celular contra la tos ferina, actualmente en uso, por una vacuna acelular combinada con una VIP.OBJECTIVE: Evaluate the cost-effectiveness of introducing the injectable inactivated polio vaccine (IPV in Colombia versus the current system based on the use of the oral vaccine (OPV. METHODS: A Markov model was designed, based on a hypothetical cohort of newborns that would receive the IPV or the OPV vaccine, with a two-year follow-up and monthly estimates of the number of cases of vaccine-associated paralytic poliomyelitis (VAPP
Foerster, Tessa; Streck, André Felipe; Speck, Stephanie; Selbitz, Hans-Joachim; Lindner, Thomas; Truyen, Uwe
Inactivated whole-virus vaccines against porcine parvovirus (PPV) can prevent disease but not infection and virus shedding after heterologous virus challenge. Here, we showed that the same is true for a homologous challenge. Pregnant sows were vaccinated with an experimental inactivated vaccine based on PPV strain 27a. They were challenged on day 40 of gestation with the virulent porcine parvovirus PPV-27a from which the vaccine was prepared (homologous challenge). On day 90 of gestation, the fetuses from vaccinated sows were protected against disease, while the fetuses of the non-vaccinated sows (control group) exhibited signs of parvovirus disease. All gilts, whether vaccinated or not vaccinated, showed a boost of PPV-specific antibodies indicative of virus infection and replication. Low DNA copy numbers, but not infectious virus, could be demonstrated in nasal or rectal swabs of immunized sows, but high copy numbers of challenge virus DNA as well as infectious virus could both be demonstrated in non-vaccinated sows.
Wang, Kun-Teng; Lin, Shih-Jie; Wang, Hsiu-Chi; Chen, Pin-Chun; Lin, Jiao-Jung; Chiang, Jen-Ron; Chang, Chao-Liang; Shih, Daniel Yang-Chih; Lo, Chi-Fang; Wang, Der-Yuan
Enterovirus 71 (EV71) belongs to the Enterovirus genus of the Picornaviridae family, and its occurrence in Asia is associated with hand-foot-and-mouth disease (HFMD), leading to death in some cases, in young children. An effective EV71 vaccine is therefore urgently needed. In this study, we established a two-step EV71 vaccine potency model. Intraperitoneal injections in 2-day-old suckling mice were used to establish the LD50 of EV71 B4, B5, C2, C4, and C5 subgenotypes. Only C4 caused hind limb paralysis in mice (LD50: 2.62 ± 0.45). EV71 VP1 protein was identified in the brain tissues at histology. In the second phase of the model, 3-week-old female ICR mice received one primary and two boosting i.p. injections of formalin-inactivated EV71 B4 and C4 vaccine. Immunized serum was neutralized in vitro with EV71 C4 and applied to the murine challenge model. The C4 vaccine-immunized serum exhibited the highest protective titre (ED50 = 114.6), while the B4 immunized serum had the weakest protective titre (ED50 = 34.3). Additionally, human plasma and intravenous immunoglobulin displayed significant protection in the neutralization assay. Our results could facilitate candidate EV71 vaccine immunogenicity and efficacy evaluations, and may help establish reference EV71 antisera in the future. Copyright © 2016 International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.
Grassly, Nicholas C
The global incidence of poliomyelitis has dropped by more than 99 per cent since the governments of the world committed to eradication in 1988. One of the three serotypes of wild poliovirus has been eradicated and the remaining two serotypes are limited to just a small number of endemic regions. However, the Global Polio Eradication Initiative (GPEI) has faced a number of challenges in eradicating the last 1 per cent of wild-virus transmission. The polio endgame has also been complicated by the recognition that vaccination with the oral poliovirus vaccine (OPV) must eventually cease because of the risk of outbreaks of vaccine-derived polioviruses. I describe the major challenges to wild poliovirus eradication, focusing on the poor immunogenicity of OPV in lower-income countries, the inherent limitations to the sensitivity and specificity of surveillance, the international spread of poliovirus and resulting outbreaks, and the potential significance of waning intestinal immunity induced by OPV. I then focus on the challenges to eradicating all polioviruses, the problem of vaccine-derived polioviruses and the risk of wild-type or vaccine-derived poliovirus re-emergence after the cessation of oral vaccination. I document the role of research in the GPEI's response to these challenges and ultimately the feasibility of achieving a world without poliomyelitis.
... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Anterior poliomyelitis. 3... Specific Diseases § 3.379 Anterior poliomyelitis. If the first manifestations of acute anterior poliomyelitis present themselves in a veteran within 35 days of termination of active military service, it is...
Alan Yung-Chih Hu
Full Text Available BACKGROUND: Highly pathogenic influenza viruses pose a constant threat which could lead to a global pandemic. Vaccination remains the principal measure to reduce morbidity and mortality from such pandemics. The availability and surging demand for pandemic vaccines needs to be addressed in the preparedness plans. This study presents an improved high-yield manufacturing process for the inactivated influenza H5N1 vaccines using Madin-Darby canine kidney (MDCK cells grown in a serum-free (SF medium microcarrier cell culture system. PRINCIPAL FINDING: The current study has evaluated the performance of cell adaptation switched from serum-containing (SC medium to several commercial SF media. The selected SF medium was further evaluated in various bioreactor culture systems for process scale-up evaluation. No significant difference was found in the cell growth in different sizes of bioreactors studied. In the 7.5 L bioreactor runs, the cell concentration reached to 2.3 × 10(6 cells/mL after 5 days. The maximum virus titers of 1024 Hemagglutinin (HA units/50 µL and 7.1 ± 0.3 × 10(8 pfu/mL were obtained after 3 days infection. The concentration of HA antigen as determined by SRID was found to be 14.1 µg/mL which was higher than those obtained from the SC medium. A mouse immunogenicity study showed that the formalin-inactivated purified SF vaccine candidate formulated with alum adjuvant could induce protective level of virus neutralization titers similar to those obtained from the SC medium. In addition, the H5N1 viruses produced from either SC or SF media showed the same antigenic reactivity with the NIBRG14 standard antisera. CONCLUSIONS: The advantages of this SF cell-based manufacturing process could reduce the animal serum contamination, the cost and lot-to-lot variation of SC medium production. This study provides useful information to manufacturers that are planning to use SF medium for cell-based influenza vaccine production.
Han, Seung Beom; Rhim, Jung-Woo; Shin, Hye Jo; Lee, Soo Young; Kim, Hyun-Hee; Kim, Jong-Hyun; Lee, Kyung-Yil; Ma, Sang Hyuk; Park, Joon Soo; Kim, Hwang Min; Kim, Chun Soo; Kim, Dong Ho; Choi, Young Youn; Cha, Sung-Ho; Hong, Young Jin; Kang, Jin Han
A multicenter, double-blind, randomized, active-control phase III clinical trial was performed to assess the immunogenicity and safety of a trivalent, inactivated split influenza vaccine. Korean children between the ages of 6 months and 18 y were enrolled and randomized into a study (study vaccine) or a control vaccine group (commercially available trivalent, inactivated split influenza vaccine) in a 5:1 ratio. Antibody responses were determined using hemagglutination inhibition assay, and post-vaccination immunogenicity was assessed based on seroconversion and seroprotection rates. For safety assessment, solicited local and systemic adverse events up to 28 d after vaccination and unsolicited adverse events up to 6 months after vaccination were evaluated. Immunogenicity was assessed in 337 and 68 children of the study and control groups. In the study vaccine group, seroconversion rates against influenza A/H1N1, A/H3N2, and B strains were 62.0% (95% CI: 56.8-67.2), 53.4% (95% CI: 48.1-58.7), and 54.9% (95% CI: 48.1-60.2), respectively. The corresponding seroprotection rates were 95.0% (95% CI: 92.6-97.3), 93.8% (95% CI: 91.2-96.4), and 95.3% (95% CI: 93.0-97.5). The lower 95% CI limits of the seroconversion and seroprotection rates were over 40% and 70%, respectively, against all strains. Seroconversion and seroprotection rates were not significantly different between the study and control vaccine groups. Furthermore, the frequencies of adverse events were not significantly different between the 2 vaccine groups, and no serious vaccination-related adverse events were noted. In conclusion, the study vaccine exhibited substantial immunogenicity and safety in Korean children and is expected to be clinically effective.
Okayasu, Hiromasa; Sein, Carolyn; Chang Blanc, Diana; Gonzalez, Alejandro Ramirez; Zehrung, Darin; Jarrahian, Courtney; Macklin, Grace; Sutter, Roland W
A fractional dose of inactivated poliovirus vaccine (fIPV) administered by the intradermal route delivers one fifth of the full vaccine dose administered by the intramuscular route and offers a potential dose-sparing strategy to stretch the limited global IPV supply while further improving population immunity. Multiple studies have assessed immunogenicity of intradermal fIPV compared with the full intramuscular dose and demonstrated encouraging results. Novel intradermal devices, including intradermal adapters and disposable-syringe jet injectors, have also been developed and evaluated as alternatives to traditional Bacillus Calmette-Guérin needles and syringes for the administration of fIPV. Initial experience in India, Pakistan, and Sri Lanka suggests that it is operationally feasible to implement fIPV vaccination on a large scale. Given the available scientific data and operational feasibility shown in early-adopter countries, countries are encouraged to consider introducing a fIPV strategy into their routine immunization and supplementary immunization activities. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.
United States Naval Medical Research Center Detachment, Lima, Peru , 1 and United States Naval Medical Research Center, Silver Spring, Maryland2 R...and 28. The mice in group B mice received 10-ng vaccine doses on study clays 0, 14, and 28. The mice in group C received 10-ng vaccine doses on
John, Jacob; Giri, Sidhartha; Karthikeyan, Arun S; Lata, Dipti; Jeyapaul, Shalini; Rajan, Anand K; Kumar, Nirmal; Dhanapal, Pavithra; Venkatesan, Jayalakshmi; Mani, Mohanraj; Hanusha, Janardhanan; Raman, Uma; Moses, Prabhakar D; Abraham, Asha; Bahl, Sunil; Bandyopadhyay, Ananda S; Ahmad, Mohammad; Grassly, Nicholas C; Kang, Gagandeep
In 2014, 2 studies showed that inactivated poliovirus vaccine (IPV) boosts intestinal immunity in children previously immunized with oral poliovirus vaccine (OPV). As a result, IPV was introduced in mass campaigns to help achieve polio eradication. We conducted an open-label, randomized, controlled trial to assess the duration of the boost in intestinal immunity following a dose of IPV given to OPV-immunized children. Nine hundred healthy children in Vellore, India, aged 1-4 years were randomized (1:1:1) to receive IPV at 5 months (arm A), at enrollment (arm B), or no vaccine (arm C). The primary outcome was poliovirus shedding in stool 7 days after bivalent OPV challenge at 11 months. For children in arms A, B, and C, 284 (94.7%), 297 (99.0%), and 296 (98.7%), respectively, were eligible for primary per-protocol analysis. Poliovirus shedding 7 days after challenge was less prevalent in arms A and B compared with C (24.6%, 25.6%, and 36.4%, respectively; risk ratio 0.68 [95% confidence interval: 0.53-0.87] for A versus C, and 0.70 [0.55-0.90] for B versus C). Protection against poliovirus remained elevated 6 and 11 months after an IPV boost, although at a lower level than reported at 1 month. CTRI/2014/09/004979. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.
Chua, Brendon Y; Wong, Chinn Yi; Mifsud, Edin J; Edenborough, Kathryn M; Sekiya, Toshiki; Tan, Amabel C L; Mercuri, Francesca; Rockman, Steve; Chen, Weisan; Turner, Stephen J; Doherty, Peter C; Kelso, Anne; Brown, Lorena E; Jackson, David C
The continual threat to global health posed by influenza has led to increased efforts to improve the effectiveness of influenza vaccines for use in epidemics and pandemics. We show in this study that formulation of a low dose of inactivated detergent-split influenza vaccine with a Toll-like receptor 2 (TLR2) agonist-based lipopeptide adjuvant (R4Pam2Cys) provides (i) immediate, antigen-independent immunity mediated by the innate immune system and (ii) significant enhancement of antigen-dependent immunity which exhibits an increased breadth of effector function. Intranasal administration of mice with vaccine formulated with R4Pam2Cys but not vaccine alone provides protection against both homologous and serologically distinct (heterologous) viral strains within a day of administration. Vaccination in the presence of R4Pam2Cys subsequently also induces high levels of systemic IgM, IgG1, and IgG2b antibodies and pulmonary IgA antibodies that inhibit hemagglutination (HA) and neuraminidase (NA) activities of homologous but not heterologous virus. Improved primary virus nucleoprotein (NP)-specific CD8(+) T cell responses are also induced by the use of R4Pam2Cys and are associated with robust recall responses to provide heterologous protection. These protective effects are demonstrated in wild-type and antibody-deficient animals but not in those depleted of CD8(+) T cells. Using a contact-dependent virus transmission model, we also found that heterologous virus transmission from vaccinated mice to naive mice is significantly reduced. These results demonstrate the potential of adding a TLR2 agonist to an existing seasonal influenza vaccine to improve its utility by inducing immediate short-term nonspecific antiviral protection and also antigen-specific responses to provide homologous and heterologous immunity. The innate and adaptive immune systems differ in mechanisms, specificities, and times at which they take effect. The innate immune system responds within hours of
The objective of this study was to compare reproductive protection in cattle against the impacts of bovine viral diarrhea virus (BVDV) provided by three different multivalent vaccines containing inactivated BVDV. Beef heifers and cows (n=122), seronegative and virus negative for BVDV, were randomly ...
Lelie, P. N.; van Amelsfoort, P. J.; Martine de Groot, C. S.; Bakker, E.; Schaasberg, W.; Niessen, J. C.; Reesink, H. W.
In a randomized, dose-response study among 305 health care workers, we examined whether the immunogenicity of a heat-inactivated hepatitis B vaccine could be enhanced when HBsAg was complexed by anti-HBs contained in hepatitis B immunoglobulin either at equivalent proportions or at 10-fold antigen
Lelie, P. N.; Reesink, H. W.; de Jong-van Manen, S. T.; Dees, P. J.; Reerink-Brongers, E. E.
The safety and immunogenicity of a plasma-derived heat-inactivated hepatitis B vaccine (CLB) were evaluated in 471 healthy human volunteers, who, both in their occupations and in their private lives, had been at minimal risk of being infected with hepatitis B virus. The first 202 individuals
M. V. Mesentseva
Full Text Available Abstract. Tick-borne encephalitis (TBE is severe neuroinfectious disease with involvement of immune mechanisms in pathogenesis. Comparative analysis of synthesis of key cytokines had been performed for the TBE virus (TBEV infected cells and in the presence of inactivated vaccine against TBE in vitro. Persistent TBEV infection of immortal tissue culture of human larynx cancer cells caused transcription activation of interferons IFNα, IFNγ, IFNλ1, interleukins IL-1β, IL-2, IL-4, IL-8, IL-10, IL-12, tumour necrosis factor TNFα as well as one of apoptosis factors Fas. Comparison of transcription and production of cytokines revealed that the TBEV infection resulted in posttranscription Th1 shift of cytokine response. In the presence of inactivated vaccine against TBE based on the same strain Sofjin of the TBEV activation of transcription of cytokines IFNα, IFNλ1, IL-4, IL-10 was also observed as after the TBEV infection that together with an additional stimulation of GM-CSF production might serve as an evidence of Th2 response. Involvement of IFNIII type (IFNλ1 both during persistent infection and after addition of inactivated vaccines was found in the first time. Differences in dynamics of cytokines IL-2, IL-8, IL-10, IL-12, TNFα response during the TBEV infection and in the presence of inactivated vaccine are described.
McElhaney, J.E.; Beran, J.; Devaster, J.M.; Esen, M.; Launay, O.; Leroux-Roels, G.; Ruiz-Palacios, G.M.; Essen, G.A. van; Caplanusi, A.; Claeys, C.; Durand, C.; Duval, X.; Idrissi, M. El; Falsey, A.R.; Feldman, G.; Frey, S.E.; Galtier, F.; Hwang, S.J.; Innis, B.L.; Kovac, M.; Kremsner, P.; McNeil, S.; Nowakowski, A.; Richardus, J.H.; Trofa, A.; Oostvogels, L.; Verheugt, F.W.; et al.,
BACKGROUND: We aimed to compare AS03-adjuvanted inactivated trivalent influenza vaccine (TIV) with non-adjuvanted TIV for seasonal influenza prevention in elderly people. METHODS: We did a randomised trial in 15 countries worldwide during the 2008-09 (year 1) and 2009-10 (year 2) influenza seasons.
Nordheim, W.; Braeuniger, S.; Schulze, P.; Dittmann, S.; Petzold, G.; Teupel, D.; Luther, P.; Tischner, H.; Baer, M.; Akademie der Wissenschaften der DDR, Leipzig. Zentralinstitut fuer Isotopen- und Strahlenforschung)
Radiation doses between 12 and 13 kGy at 15-20 0 C were sufficient for mild inactivation of influenza viruses. Under these conditions the decisive surface antigens hemagglutinin and neuraminidase were treated with care, and the preparations of influenza viruses revealed good immunogenicity in the animal experiment. Morphologic alterations after application of 20 kGy could not be demonstrated in electron microscopic investigations. Doses of 9.5-9.9 kGy in combination with a very low quantity of HCHO (1:15000) is sufficient for inactivation. Reactivation of influenza viruses after treatment could not be demonstrated. (author)
Zerbini, Cristiano A F; Ribeiro Dos Santos, Rodrigo; Jose Nunes, Maria; Soni, Jyoti; Li, Ping; Jain, Varsha K; Ofori-Anyinam, Opokua
The World Health Organization influenza forecast now includes an influenza B strain from each of the influenza B lineages (B/Yamagata and B/Victoria) for inclusion in seasonal influenza vaccines. Traditional trivalent influenza vaccines include an influenza B strain from one lineage, but because two influenza B lineages frequently co-circulate, the effectiveness of trivalent vaccines may be reduced in seasons of influenza B vaccine-mismatch. Thus, quadrivalent vaccines may potentially reduce the burden of influenza compared with trivalent vaccines. In this Phase III, open-label study, we assessed the immunogenicity and safety of Southern Hemisphere inactivated quadrivalent influenza vaccine (Fluarix™ Tetra) in Brazilian adults (NCT02369341). The primary objective was to assess hemagglutination-inhibition antibody responses against each vaccine strain 21 days after vaccination in adults (aged ≥18-60 years) and older adults (aged >60 years). Solicited adverse events for four days post-vaccination, and unsolicited adverse events and serious adverse events for 21 days post-vaccination were also assessed. A total of 63 adults and 57 older adults received one dose of inactivated quadrivalent influenza vaccine at the beginning of the 2015 Southern Hemisphere influenza season. After vaccination, in adults and older adults, the hemagglutination-inhibition titers fulfilled the European licensure criteria for immunogenicity. In adults, the seroprotection rates with HI titer ≥1:40 were 100% (A/H1N1), 98.4% (A/H3N2), 100% (B/Yamagata), and 100% (B/Victoria); in older adults were 94.7% (A/H1N1), 96.5% (A/H3N2), 100% (B/Yamagata), and 100% (B/Victoria). Pain was the most common solicited local adverse events in adults (27/62) and in older adults (13/57), and the most common solicited general adverse events in adults was myalgia (9/62), and in older adults were myalgia and arthralgia (both 2/57). Unsolicited adverse events were reported by 11/63 adults and 10/57 older adults
Liao, Guoyang; Li, Rongcheng; Li, Changgui; Sun, Mingbo; Li, Yanping; Chu, Jiayou; Jiang, Shude; Li, Qihan
The production of Sabin inactivated poliovirus vaccine (IPV) can reduce biosafety requirements in the posteradication/post-oral poliovirus vaccine (OPV) era. We conducted a phase II, randomized, positive-controlled trial to assess the safety and immunogenicity of Sabin IPV. The test groups (A, B, and C) received 3 doses of high, middle, and low D antigen (D Ag) of Sabin IPV at ages 2, 3, and 4 months, respectively. Infants in 2 control groups, group D and group E, received 3 doses of trivalent OPV and conventional IPV (cIPV), respectively, on the same schedule as that of groups A, B, and C. Serum samples were collected before and 30 days after the administration of the third dose. In total, 500 infants were randomly assigned to 5 groups, and 449 infants completed the vaccine series. No serious adverse events were associated with vaccinations. After 3 doses, the seroconversion rates in groups A, B, C, D, and E were 100%, 97.8%, 96.6%, 100%, and 90.1%, respectively, for type 1 poliovirus; 97.7%, 95.7%, 78.7%, 100%, and 90.1%, respectively, for type 2; and 98.8%, 98.9%, 93.3%, 100%, and 97.8%, respectively, for type 3. Sabin IPV has good safety characteristics. The seroconversion rates for type 1 poliovirus (most appropriate concentration, 15 D Ag units [DU]), type 2 (32 DU), and type 3 (45 DU) Sabin IPV were similar to those of the OPV and cIPV control groups. NCT01056705.
Sheikh, Mohamed A; Makokha, Frederick; Hussein, Abdullahi M; Mohamed, Gedi; Mach, Ondrej; Humayun, Kabir; Okiror, Samuel; Abrar, Leila; Nasibov, Orkhan; Burton, John; Unshur, Ahmed; Wannemuehler, Kathleen; Estivariz, Concepcion F
Since the launch of the Global Polio Eradication Initiative (GPEI) in 1988, circulation of indigenous wild poliovirus (WPV) has continued without interruption in only three countries: Afghanistan, Nigeria, and Pakistan. During April-December 2013, a polio outbreak caused by WPV type 1 (WPV1) of Nigerian origin resulted in 217 cases in or near the Horn of Africa, including 194 cases in Somalia, 14 cases in Kenya, and nine cases in Ethiopia (all cases were reported as of March 10, 2014). During December 14-18, 2013, Kenya conducted the first-ever campaign providing inactivated poliovirus vaccine (IPV) together with oral poliovirus vaccine (OPV) as part of its outbreak response. The campaign targeted 126,000 children aged ≤59 months who resided in Somali refugee camps and surrounding communities near the Kenya-Somalia border, where most WPV1 cases had been reported, with the aim of increasing population immunity levels to ensure interruption of any residual WPV transmission and prevent spread from potential new importations. A campaign evaluation and vaccination coverage survey demonstrated that combined administration of IPV and OPV in a mass campaign is feasible and can achieve coverage >90%, although combined IPV and OPV campaigns come at a higher cost than OPV-only campaigns and require particular attention to vaccinator training and supervision. Future operational studies could assess the impact on population immunity and the cost-effectiveness of combined IPV and OPV campaigns to accelerate interruption of poliovirus transmission during polio outbreaks and in certain areas in which WPV circulation is endemic.
Turner, Nikki; Pierse, Nevil; Bissielo, Ange; Huang, Q Sue; Baker, Michael G; Widdowson, Marc-Alain; Kelly, Heath
Few studies report the effectiveness of trivalent inactivated influenza vaccine (TIV) in preventing hospitalisation for influenza-confirmed respiratory infections. Using a prospective surveillance platform, this study reports the first such estimate from a well-defined ethnically diverse population in New Zealand (NZ). A case test-negative design was used to estimate propensity adjusted vaccine effectiveness. Patients with a severe acute respiratory infection (SARI), defined as a patient of any age requiring hospitalisation with a history of a fever or a measured temperature ≥38°C and cough and onset within the past 7 days, admitted to public hospitals in South and Central Auckland were eligible for inclusion in the study. Cases were SARI patients who tested positive for influenza, while non-cases (controls) were SARI patients who tested negative. Results were adjusted for the propensity to be vaccinated and the timing of the influenza season. The propensity and season adjusted vaccine effectiveness (VE) was estimated as 39% (95% CI 16;56). The VE point estimate against influenza A (H1N1) was lower than for influenza B or influenza A (H3N2) but confidence intervals were wide and overlapping. Estimated VE was 59% (95% CI 26;77) in patients aged 45-64 years but only 8% (-78;53) in those aged 65 years and above. Prospective surveillance for SARI has been successfully established in NZ. This study for the first year, the 2012 influenza season, has shown low to moderate protection by TIV against influenza positive hospitalisation. Copyright © 2014 Elsevier Ltd. All rights reserved.
Turner, Nikki; Pierse, Nevil; Bissielo, Ange; Huang, Q Sue; Baker, Michael; Widdowson, Marc-Alain; Kelly, Heath
Background Few studies report the effectiveness of trivalent inactivated influenza vaccine (TIV) in preventing hospitalisation for influenza-confirmed respiratory infections. Using a prospective surveillance platform, this study reports the first such estimate from a well-defined ethnically diverse population in New Zealand (NZ). Methods A case test-negative study was used to estimate propensity adjusted vaccine effectiveness. Patients with a severe acute respiratory infection (SARI), defined as a patient of any age requiring hospitalization with a history of a fever or a measured temperature ≥38°C and cough and onset within the past 7 days, admitted to public hospitals in Central, South and East Auckland were eligible for inclusion in the study. Cases were SARI patients who tested positive for influenza, while non-cases (controls) were SARI patients who tested negative. Results were adjusted for the propensity to be vaccinated and the timing of the influenza season Results The propensity and season adjusted vaccine effectiveness (VE) was estimated as 37% (95% CI 18;51). The VE point estimate against influenza A (H1N1) was higher than for influenza B or influenza A (H3N2) but confidence intervals were wide and overlapping. Estimated VE was 51% (95% CI 28;67) in patients aged 18-64 years but only 6% (95% CI -51;42) in those aged 65 years and above. Conclusion Prospective surveillance for SARI has been successfully established in NZ . This study for the first year, the 2012 influenza season, has shown low to moderate protection by TIV against hospitalisation for laboratory-confirmed influenza. PMID:24768730
Zhang, Wei; Kong, Yujia; Jiang, Zhiwei; Li, Chanjuan; Wang, Ling; Xia, Jielai
Human enterovirus 71 (EV71) is a causative agent of hand, foot, and mouth disease (HFMD). In a previous phase III trial in children, a human diploid cell-based inactivated EV71 vaccine elicited EV71 specific immune responses and protection against EV71 associated HFMD. This study aimed to assess the factors influencing the severity of adverse events observed in this previous trial. This was a randomized, double-blinded, placebo-controlled, phase III clinical trial of a human diploid vaccine carried out in 12,000 children in Guangxi Zhuang Autonomous Region, China (ClinicalTrials.gov: NCT01569581). Solicited events were recorded for 7 days and unsolicited events were reported for 28 days after each injection. Age trend analysis of adverse reaction was conducted in each treatment group. Multiple logistic regression models were built to identify factors influencing the severity of adverse reactions. Fewer solicited adverse reactions were observed in older participants within the first 7 days after vaccination (P < 0.0001), except local pain and pruritus. More severe adverse reactions were observed after the initial injection than after the booster injection. Serious cold or respiratory tract infections (RTI) were observed more often in children aged 6-36 months than in older children. Only the severity of local swelling was associated with body mass index. Children with throat discomfort before injection had a higher risk of serious cold or RTI. These results indicated that the human diploid cell-based vaccine achieved a satisfactory safety profile.
Fahmy, Kamal; Hampton, Lee M; Langar, Houda; Patel, Manish; Mir, Tahir; Soloman, Chandrasegarar; Hasman, Andreas; Yusuf, Nasir; Teleb, Nadia
The Global Polio Eradication Initiative has reduced the global incidence of polio by 99% and the number of countries with endemic polio from 125 to 3 countries. The Polio Eradication and Endgame Strategic Plan 2013-2018 (Endgame Plan) was developed to end polio disease. Key elements of the endgame plan include strengthening immunization systems using polio assets, introducing inactivated polio vaccine (IPV), and replacing trivalent oral polio vaccine with bivalent oral polio vaccine ("the switch"). Although coverage in the Eastern Mediterranean Region (EMR) with the third dose of a vaccine containing diphtheria, tetanus, and pertussis antigens (DTP3) was ≥90% in 14 countries in 2015, DTP3 coverage in EMR dropped from 86% in 2010 to 80% in 2015 due to civil disorder in multiple countries. To strengthen their immunization systems, Pakistan, Afghanistan, and Somalia developed draft plans to integrate Polio Eradication Initiative assets, staff, structure, and activities with their Expanded Programmes on Immunization, particularly in high-risk districts and regions. Between 2014 and 2016, 11 EMR countries introduced IPV in their routine immunization program, including all of the countries at highest risk for polio transmission (Afghanistan, Pakistan, Somalia, and Yemen). As a result, by the end of 2016 all EMR countries were using IPV except Egypt, where introduction of IPV was delayed by a global shortage. The switch was successfully implemented in EMR due to the motivation, engagement, and cooperation of immunization staff and decision makers across all national levels. Moreover, the switch succeeded because of the ability of even the immunization systems operating under hardship conditions of conflict to absorb the switch activities. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.
Antigen uptake and expression of antigen presentation-related immune genes in flounder (Paralichthys olivaceus) after vaccination with an inactivated Edwardsiella tarda immersion vaccine, following hyperosmotic treatment.
Gao, Yingli; Tang, Xiaoqian; Sheng, Xiuzhen; Xing, Jing; Zhan, Wenbin
Antigen uptake is a critical process for activation of the immune system, and therefore the ability to enhance antigen uptake is a primary consideration in the development of an immersion vaccination of fish. In the present work, flounders (Paralichthys olivaceus) were immersed in three hyperosmotic solutions with 40, 50 and 60‰ salinities, then transferred into seawater of normal salinity (i.e. 30‰) containing formalin-inactivated Edwardsiella tarda for 30 min. The antigen uptake in vaccinated flounder was determined using an absolute quantitative PCR (qPCR). The results showed significantly higher antigen uptake in the tissues of flounders immersed in solutions with 50‰ and 60‰ salinity compared to the control group directly immersed in vaccine (DI) (P immersed in the 50‰ salinity solution, whereas there was no significant difference in antigen uptake between the 40‰ salinity group and the DI group (P > 0.05). A rapid and significant increase in antigen uptake was detected in the mucosal-associated tissues including the gill, skin and intestine (P immersion, which was significantly higher than the levels of uptake measured in the other tissues (P immersion (hpi). The expression profiles of four antigen presentation-related immune genes (MHC Iα, MHC IIα, CD4-1 and CD8α) were investigated after immersion. These four genes showed a significantly stronger response in the immersed flounders exposed to 50‰ salinity compared with the DI group (P immersion, notably 50‰ salinity significantly enhanced antigen uptake and the expression of selected genes associated with antigen presentation, providing evidence for an enhanced immune activation of the fish's immune response by the hyperosmotic immersion treatment prior to vaccination. Copyright © 2016 Elsevier Ltd. All rights reserved.
... people with certain health conditions or a weakened immune system are at greatest risk. Each year thousands of people in the United States die from flu , and many more are hospitalized. Flu vaccine can: • ...
Full Text Available Clinical trial for polymer-subunit trivalent influenza vaccine Grippol plus reactogenicity assessment in 153 children aged 3–17 years old was conducted in the frames of post-registration studies. Prior to the vaccination the written informed agreement was signed by every participant’ parent. In post-vaccination period physical examination and thermometry was performed daily in post-immunization days 1–5, on days 21–28 and then on a monthly basis for 4 months. Study results demonstrated that Grippol plus possesses low reactogenicity and can be applied in pediatrics for immunization in accordance with National Immunization schedule.Key words: children, influenza, vaccination.(Voprosy sovremennoi pediatrii — Current Pediatrics. 2009;8(4:37-41
9 avr. 2018 ... Les vaccins actuels contre la cowdriose ne sont pas très efficaces car ils protègent seulement contre un seul génotype, mais bon nombre de souches de la maladie peuvent être présentes dans la même zone. Quant aux vaccins contre la PPCC, ils sont produits à l'aide de cultures de la bactérie Mccp et ...
Lee, D-H; Kwon, J-S; Lee, H-J; Lee, Y-N; Hur, W; Hong, Y-H; Lee, J-B; Park, S-Y; Choi, I-S; Song, C-S
The frequent economic losses incurred with H9N2 low pathogenic avian influenza viruses (LPAI) infection have raised serious concerns for the poultry industry. A 1-dose regimen with inactivated H9N2 LPAI vaccine could not prevent vaccinated poultry from becoming infected and from shedding wild viruses. A study was conducted to determine whether a 2-dose regimen of inactivated H9N2 LPAI vaccine could enhance the immunologic response in chickens. Such gel-primed and mineral oil-boosted regimen has produced encouraging results associated with improved immune responses to an H9N2 LPAI. This strategy could be cost effective and helpful for preventing avian influenza virus in the poultry industry.
Khuri-Bulos, Najwa; Melnick, Joseph L.; Hatch, Milford H.; Dawod, Saleh T.
Poliomyelitis is endemic in Jordan, but until 1978 there were no epidemics. In that year, 66 children were admitted to the Jordan University Hospital with a paralytic illness, compared with 13 in 1979 and 11 in 1980. The epidemic reached a peak in the summer and fall of 1978. While 54% of the patients had not received any vaccine, 19% had received 3 doses of oral poliovaccine; 82% of the cases were in children less than 2 years of age, and all belonged to the lower socioeconomic group. There were 28 deaths with complications of the disease. Poliovirus was isolated from 10 out of 14 rectal swab samples examined (9 with poliovirus 1, 1 with poliovirus 2), and from 4 out of 13 throat specimens from the same patients. It is concluded that as a result of improving living standards in Jordan and neighbouring countries, more epidemics may occur unless immunization efforts against poliomyelitis are intensified. PMID:6609022
Lucia Ferro Bricks
, from January 2000 to December 2006. DATA SYNTHESIS: Acknowledgement of vaccine-associated paralysis and oral vaccine-derived circulating viruses’ paralysis shall certainly require discontinuation of oral vaccination for poliomyelitis use in a short time. After eradication of the wild viruses, oral vaccination for poliomyelitis should be discontinued, preferably in a synchronized manner in all the countries. After termination of vaccination programs, people will become susceptible again to poliomyelitis virus and disease outbreaks caused by wild viruses may occur (accidental escape from laboratories or bioterrorism. In countries already using inactivated poliovirus vaccine, it is unlikely that vaccination will be interrupted. Countries that currently use exclusively oral poliovirus vaccine will have to rely on epidemiological surveillance and on oral vaccine inventories to control potential polio outbreaks. If the oral poliovirus vaccine is reintroduced in those populations, there will be again a risk for vaccine-associated paralysis and oral vaccine-derived circulating viruses’ that may spread rapidly to other regions and to nearby countries. CONCLUSIONS: Inactivated poliovirus vaccine introduction in the routine Brazilian vaccination calendar should be programmed as well as acquisition of technology for inactivated poliovirus vaccine production since the latter is currently insufficient to cover global demand.
Full Text Available Jean-Eric Tarride,1,2 Natasha Burke,1,2 Camilla Von Keyserlingk,1,2 Daria O'Reilly,1,2 Feng Xie,1,2 Ron Goeree1,21Programs for Assessment of Technology in Health (PATH Research Institute, St Joseph's Healthcare Hamilton, Hamilton, 2Department of Clinical Epidemiology and Biostatistics, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, CanadaBackground: Influenza affects all age groups and is common in children. Between 15% and 42% of preschool- and school-aged children experience influenza each season. Recently, intranasal live attenuated influenza vaccine, trivalent (LAIV has been approved in Canada.Objective: The objective of this study was to determine the cost-effectiveness of LAIV compared with that of the injectable inactivated influenza vaccine, trivalent (TIV in Canadian children and adolescents from both a payer (eg. Ministry of Health perspective and a societal perspective.Methods: A cost-effectiveness model comparing LAIV and TIV in children aged 24–59 months old was supplemented by primary (ie, a survey of 144 Canadian physicians and secondary (eg, literature data to model children aged 2–17 years old. Parameter uncertainty was addressed through univariate and probability analyses.Results: Although LAIV increased vaccination costs when compared to TIV, LAIV reduced the number of influenza cases and lowered the number of hospitalizations, emergency room visits, outpatient visits, and parents’ days lost from work. The estimated offsets in direct and societal costs saved were CAD$4.20 and CAD$35.34, respectively, per vaccinated child aged 2–17 years old. When costs and outcomes were considered, LAIV when compared to TIV, was the dominant strategy. At a willingness to pay of CAD$50,000 per quality adjusted life year gained, or CAD$100,000 per quality adjusted life year gained, the probabilistic results indicated that the probability of LAIV being cost-effective was almost 1.Conclusions: LAIV reduces the burden
Paillot, R; Prowse, L; Montesso, F; Huang, C M; Barnes, H; Escala, J
Equine influenza (EI) is a serious respiratory disease of horses induced by the equine influenza virus (EIV). Surveillance, quarantine procedures and vaccination are widely used to prevent or to contain the disease. This study aimed to further characterise the immune response induced by a non-updated inactivated EI and tetanus vaccine, including protection against a representative EIV isolate of the Florida clade 2 sublineage. Seven ponies were vaccinated twice with Duvaxyn IE-T Plus at an interval of four weeks. Five ponies remained unvaccinated. All ponies were experimentally infected with the EIV strain A/eq/Richmond/1/07 two weeks after the second vaccination. Clinical signs of disease were recorded and virus shedding was measured after experimental infection. Antibody response and EIV-specific IFNgamma synthesis, a marker of cell-mediated immunity, were measured at different time points of the study. Vaccination resulted in significant protection against clinical signs of disease induced by A/eq/Richmond/1/07 and reduced virus shedding when challenged at the peak of immunity. Antigenic drift has been shown to reduce protection against EIV infection. Inclusion of a more recent and representative EIV vaccine strain, as recommended by the OIE expert surveillance panel on equine influenza vaccine, may maximise field protection. In addition, significant levels of EIV-specific IFNgamma synthesis by peripheral blood lymphocytes were detected in immunised ponies, which provided a first evidence of CMI stimulation after vaccination with a whole inactivated EIV. Duration of humoral response was also retrospectively investigated in 14 horses vaccinated under field condition and following the appropriate immunisation schedule, up to 599 days after first immunisation. This study revealed that most immunised horses maintained significant levels of cross-reactive SRH antibody for a prolonged period of time, but individual monitoring may be beneficial to identify poor vaccine
Luo, Hui-Ming; Zhang, Yong; Wang, Xin-Qi; Yu, Wen-Zhou; Wen, Ning; Yan, Dong-Mei; Wang, Hua-Qing; Wushouer, Fuerhati; Wang, Hai-Bo; Xu, Ai-Qiang; Zheng, Jing-Shan; Li, De-Xin; Cui, Hui; Wang, Jian-Ping; Zhu, Shuang-Li; Feng, Zi-Jian; Cui, Fu-Qiang; Ning, Jing; Hao, Li-Xin; Fan, Chun-Xiang; Ning, Gui-Jun; Yu, Hong-Jie; Wang, Shi-Wen; Liu, Da-Wei; Wang, Dong-Yan; Fu, Jian-Ping; Gou, Ai-li; Zhang, Guo-Min; Huang, Guo-Hong; Chen, Yuan-Sheng; Mi, Sha-Sha; Liu, Yan-Min; Yin, Da-Peng; Zhu, Hui; Fan, Xin-Chun; Li, Xin-Lan; Ji, Yi-Xin; Li, Ke-Li; Tang, Hai-Shu; Xu, Wen-Bo; Wang, Yu; Yang, Wei-Zhong
The last case of infection with wild-type poliovirus indigenous to China was reported in 1994, and China was certified as a poliomyelitis-free region in 2000. In 2011, an outbreak of infection with imported wild-type poliovirus occurred in the province of Xinjiang. We conducted an investigation to guide the response to the outbreak, performed sequence analysis of the poliovirus type 1 capsid protein VP1 to determine the source, and carried out serologic and coverage surveys to assess the risk of viral propagation. Surveillance for acute flaccid paralysis was intensified to enhance case ascertainment. Between July 3 and October 9, 2011, investigators identified 21 cases of infection with wild-type poliovirus and 23 clinically compatible cases in southern Xinjiang. Wild-type poliovirus type 1 was isolated from 14 of 673 contacts of patients with acute flaccid paralysis (2.1%) and from 13 of 491 healthy persons who were not in contact with affected persons (2.6%). Sequence analysis implicated an imported wild-type poliovirus that originated in Pakistan as the cause of the outbreak. A public health emergency was declared in Xinjiang after the outbreak was confirmed. Surveillance for acute flaccid paralysis was enhanced, with daily reporting from all public and private hospitals. Five rounds of vaccination with live, attenuated oral poliovirus vaccine (OPV) were conducted among children and adults, and 43 million doses of OPV were administered. Trivalent OPV was used in three rounds, and monovalent OPV type 1 was used in two rounds. The outbreak was stopped 1.5 months after laboratory confirmation of the index case. The 2011 outbreak in China showed that poliomyelitis-free countries remain at risk for outbreaks while the poliovirus circulates anywhere in the world. Global eradication of poliomyelitis will benefit all countries, even those that are currently free of poliomyelitis.
SHIRAISHI, Rikiya; NISHIMURA, Masaaki; NAKASHIMA, Ryuji; ENTA, Chiho; HIRAYAMA, Norio
ABSTRACT In Japan, the import quarantine regulation against rabies has required from 2005 that dogs and cats should be inoculated with the rabies vaccine and that the neutralizing antibody titer should be confirmed to be at least 0.5 international units (IU)/ml. The fluorescent antibody virus neutralization (FAVN) test is used as an international standard method for serological testing for rabies. To achieve proper immunization of dogs and cats at the time of import and export, changes in the neutralizing antibody titer after inoculation of the rabies vaccine should be understood in detail. However, few reports have provided this information. In this study, we aimed to determine evaluated, such changes by using sera from experimental dogs and cats inoculated with the rabies vaccine, and we tested samples using the routine FAVN test. In both dogs and cats, proper, regular vaccination enabled the necessary titer of neutralizing antibodies to be maintained in the long term. However, inappropriate timing of blood sampling after vaccination could result in insufficient detected levels of neutralizing antibodies. PMID:24389741
Full Text Available Streptococcus iniae is a causative agent of hemorrhagic septicemia in olive flounder, Paralichthys olivaceus, in Korea, resulting in serious economic losses. As a preventive measure, M VAC INIAE (Mastuken, Japan was prepared from the S. iniae F2K strain and tested against the SI-36 strain prevalent on flounder fish farms on Jeju Island, Korea. F2K had a serotype of 38 (− and SI-36 38 (+. The vaccine recognized both serotypes. It showed a very high effective immune response against S. iniae; the challenge test using the S. iniae SI-36 strain resulted in a relative percent survival (RPS of 85.7-87.0% 2 weeks after vaccination and 71.0-80.0% 6 months after vaccination. Field vaccination and clinical challenge tests were performed at local Jeju aquafarms with S. iniae SI-36. These showed significantly reduced cumulative mortality when compared to the control group with RPS rates that ranged between 71-80%. Hence, the present study suggests that this vaccine showed a significant immune response against S. iniae and could be applied in commercial aquafarms as a therapeutic agent against β-hemolytic streptococcosis in cultured P. olivaceus.
Anand, Abhijeet; Molodecky, Natalie A; Pallansch, Mark A; Sutter, Roland W
The polio eradication endgame strategic plan calls for the sequential removal of Sabin poliovirus serotypes from the trivalent oral poliovirus vaccine (tOPV), starting with type 2, and the introduction of ≥1 dose of inactivated poliovirus vaccine (IPV), to maintain an immunity base against poliovirus type 2. The global removal of oral poliovirus type 2 was successfully implemented in May 2016. However, IPV supply constraints has prevented introduction in 21 countries and led to complete stock-out in >20 countries. We conducted a literature review and contacted corresponding authors of recent studies with fractional-dose IPV (fIPV), one-fifth of intramuscular dose administered intradermally, to conduct additional type 2 immunogenicity analyses of two fIPV doses compared with one full-dose IPV. Four studies were identified that assessed immunogenicity of two fIPV doses compared to one full-dose IPV. Two fractional doses are more immunogenic than 1 full-dose, with type 2 seroconversion rates improving between absolute 19-42% (median: 37%, pvaccine compared to one full-dose IPV. In response to the current IPV shortage, a schedule of two fIPV doses at ages 6 and 14weekshas been endorsed by technical oversight committees and has been introduced in some affected countries. Copyright © 2017. Published by Elsevier Ltd.
An Open-Label, Randomized Study of a 9-Valent Human Papillomavirus Vaccine Given Concomitantly with Diphtheria, Tetanus, Pertussis, and Poliomyelitis Vaccines to Healthy Adolescents 11 to 15 Years of Age
Kosalaraksa, Pope; Mehlsen, Jesper; Vesikari, Timo
.8% in both groups at month 7. For REPEVAX, noninferiority of immune response was established for diphtheria, tetanus, and all polio and pertussis antigens for both groups. There were no vaccine-related serious AEs. CONCLUSION: Overall, concomitant administration of 9vHPV vaccine and REPEVAX was generally...
Andréa de Cássia RODRIGUES da SILVA
Full Text Available Despite the absence of current official reports showing the number of cattle infected by rabies, it is estimated that nearly 30,000 bovines are lost each year in Brazil. In order to minimize the important economic losses, control of the disease is achieved by eliminating bat colonies and by herd vaccination. In this study, we compare the antibody response in cattle elicited by vaccination with an attenuated ERA vaccine (AEvac and an inactivated-adjuvanted PV (IPVvac vaccine. The antibody titers were appraised by cell-culture neutralization test and ELISA, and the percentage of seropositivity was ascertained for a period of 180 days. IPVvac elicited complete seropositivity rates from day 30 to day 150, and even on day 180, 87% of the sera showed virus-neutralizing antibody titers (VNA higher than 0.5IU/ml. There were no significant differences between the VNA titers and seropositivity rates obtained with IPVvac in the two methods tested. AEvac, however, elicited significantly lower titers than those observed in the group receiving inactivated vaccine. In addition, the profiles of antirabies IgG antibodies, evaluated by ELISA, and VNA, appraised by cell-culture neutralization test, were slightly different, when both vaccines were compared.A raiva bovina, transmitida principalmente pelo morcego hematófago Desmodus rotundus, é endêmica em várias regiões do Brasil, com um crescente número de casos sendo registrados anualmente. O controle desta infecção em bovinos é feito pelo controle de colônias de morcegos hematófagos e pela vacinação dos rebanhos. Embora as vacinas inativadas sejam mais seguras e mais estáveis que as vacinas atenuadas, estas últimas são ainda amplamente utilizadas em muitas regiões do país, por se acreditar que confiram imunidade mais duradoura. Neste estudo, foram comparadas as respostas anticórpicas de dois grupos de bovinos imunizados com uma vacina atenuada e uma inativada disponíveis comercialmente. Os
Sanders, Barbara P; de Los Rios Oakes, Isabel; van Hoek, Vladimir; Bockstal, Viki; Kamphuis, Tobias; Uil, Taco G; Song, Yutong; Cooper, Gillian; Crawt, Laura E; Martín, Javier; Zahn, Roland; Lewis, John; Wimmer, Eckard; Custers, Jerome H H V; Schuitemaker, Hanneke; Cello, Jeronimo; Edo-Matas, Diana
The poliovirus vaccine field is moving towards novel vaccination strategies. Withdrawal of the Oral Poliovirus Vaccine and implementation of the conventional Inactivated Poliovirus Vaccine (cIPV) is imminent. Moreover, replacement of the virulent poliovirus strains currently used for cIPV with attenuated strains is preferred. We generated Cold-Adapted Viral Attenuation (CAVA) poliovirus strains by serial passage at low temperature and subsequent genetic engineering, which contain the capsid sequences of cIPV strains combined with a set of mutations identified during cold-adaptation. These viruses displayed a highly temperature sensitive phenotype with no signs of productive infection at 37°C as visualized by electron microscopy. Furthermore, decreases in infectious titers, viral RNA, and protein levels were measured during infection at 37°C, suggesting a block in the viral replication cycle at RNA replication, protein translation, or earlier. However, at 30°C, they could be propagated to high titers (9.4-9.9 Log10TCID50/ml) on the PER.C6 cell culture platform. We identified 14 mutations in the IRES and non-structural regions, which in combination induced the temperature sensitive phenotype, also when transferred to the genomes of other wild-type and attenuated polioviruses. The temperature sensitivity translated to complete absence of neurovirulence in CD155 transgenic mice. Attenuation was also confirmed after extended in vitro passage at small scale using conditions (MOI, cell density, temperature) anticipated for vaccine production. The inability of CAVA strains to replicate at 37°C makes reversion to a neurovirulent phenotype in vivo highly unlikely, therefore, these strains can be considered safe for the manufacture of IPV. The CAVA strains were immunogenic in the Wistar rat potency model for cIPV, inducing high neutralizing antibody titers in a dose-dependent manner in response to D-antigen doses used for cIPV. In combination with the highly productive
Soltani, Jafar; Jamil Amjadi, Mohamad
We studied the safety of a trivalent inactivated surface antigen (split virion, inactivated) influenza vaccine, Begrivac® (Novartis Company), widely used in health care workers in Kurdistan. A longitudinal follow-up study was performed in Sanandaj city, west of Iran, recruiting 936 people. A questionnaire was completed for each participant, and all symptoms or abnormal physical findings were recorded. In part 1 of the study, the post-vaccination complaints were headache (5.3%), fever (7.9%), weakness (9.6%), chills (10.1%), sweating (10.5%), arthralgia (20.2%), and malaise (21.5%). Swelling of the injection site was seen in 267 (30.3%) participants, and pruritus of the injection site was seen in 290 (32.9%) participants. Redness and induration were also reported in 42.5% of the participants. Local reactions were mainly mild and lasted for 1-2 days. No systemic reactions were reported in the second part of the study. None of the participants experienced any inconvenience. We concluded that local adverse reactions after the trivalent inactivated split influenza vaccine, Begrivac®, in health care workers were far more common than expected. Continuous surveillance is needed to assess the potential risks and benefits of newly produced influenza vaccines.
Wang, Jingjing; Qi, Sudong; Zhang, Xiaolong; Zhang, Ying; Liu, Longding; Che, Yanchun; He, Zhanlong; Zhao, Yuan; Lu, Shuaiyao; Yu, Wenhai; Li, Qihan
Hand, foot and mouth disease is usually caused by enterovirus 71 (EV71) and coxsackievirus A 16 (CA16), which are members of the Picornaviridae family. In the present study, the characteristics of the immune response induced by an EV71 inactivated vaccine (made from human diploid cells) were explored in the presence of CA16 infection, based on the previously established neonatal rhesus monkey model. The typical clinical manifestations, including body temperature, viral viremia and virus shedding in the mouth, pharynx and feces, were characterized. A specific neutralizing antibody assay showed that the specific immune response induced by the EV71 inactivated vaccine was active against EV71 but not against CA16. No remarkable fluctuation in proinflammatory cytokine release was identified in the serum of immunized monkeys with EV71 vaccine and CA16 infections subsequently. The results showed that the specific immune response induced by the EV71 inactivated vaccine is effective against EV71 infection but is not affected by CA16 infection. Copyright © 2014 Elsevier Ltd. All rights reserved.
Conclusion: The decay of poliovirus antibodies over a 21–22-month period was similar regardless of the type of booster vaccine used, suggesting the scientific data of Salk IPV long-term persistence and decay may be broadly applicable to Sabin IPV.
In order to augment responses to respiratory vaccines in swine, various adjuvants were intranasally co-administered with an antigen to pigs. Detoxified E. coli enterotoxins LTK63 and LTR72 enhanced mucosal and systemic immunity to the model peptide, exhibiting their efficacy as mucosal adjuvants for...
utilisation des terres que le bétail; ils sont donc une source importante de sécurité alimentaire et économique pour ... Une plateforme pour la mise au point d'un vaccin anti-adénovirus non réplicatif contre les maladies aviaires.
Bublot, Michel; Le Gros, François-Xavier; Nieddu, Daniela; Pritchard, Nikki; Mickle, Thomas R; Swayne, David E
The objective of this study was to compare the efficacy of two avian influenza (AI) H5-inactivated vaccines containing either an American (A/turkey/Wisconsin/68 H5N9; H5N9-WI) or a Eurasian isolate (A/chicken/Italy/22A/98 H5N9; H5N9-It). Three-week-old specific pathogen-free chickens were vaccinated once and challenged 3 wk later with a H5N1 highly pathogenic AI (HPAI) virus isolated from a chicken in Thailand in 2004. All unvaccinated challenged birds died within 2 days, whereas 90% and 100% of chickens vaccinated with H5N9-WI and H5N9-It, respectively, were protected against morbidity and mortality. Both vaccines prevented cloacal shedding and significantly reduced oral shedding of the challenge HPAI virus. Additional chickens (vaccinated or unvaccinated) were placed in contact with the directly challenged birds 18 hr after challenge. All unvaccinated chickens in contact with unvaccinated challenged birds died within 3 days after contact, whereas unvaccinated chickens in contact with vaccinated challenged birds either showed a significantly delayed mortality or did not become infected. All vaccinated contacts were protected against clinical signs, and most chickens did not shed detectable amount of HPAI virus. Altogether, these data indicate that both vaccines protected very well against morbidity and mortality and reduced or prevented shedding induced by direct or contact exposure to Asian H5N1 HPAI virus.
Di Trani, L; Cordioli, P; Falcone, E; Lombardi, G; Moreno, A; Sala, G; Tollis, M
The minimum requirements for assessing the immunogenicity of an experimental avian influenza (AI) vaccine prepared from inactivated A/Turkey/Italy/2676/99 (H7N1) low-pathogenicity (LP) AI (LPAI) virus were determined in chickens of different ages. A correlation between the amount of hemagglutinin (HA) per dose of vaccine and the protection against clinical signs of disease and infection by A/Chicken/Italy/13474/99 highly pathogenic (HP) AI (HPAI) virus was established. Depending on the vaccination schedule, one or two administrations of 0.5 microg of hemagglutinin protected chickens against clinical signs and death and completely prevented virus shedding from birds challenged at different times after vaccination.
Knowledge assessment regarding poliomyelitis among the caregivers of children who received oral polio vaccine reveals lack of awareness of the vaccine vial monitor (VVM): Implications extending beyond polio eradication.
Bhilwar, Meenakshi; Lal, Panna
Vaccine vial monitor (VVM) is now commonly used for vaccines that are included in the National Immunization Schedule in India. It helps to indicate the viability of the vaccine and of the proper functioning of the cold chain. This is useful as it prevents health personnel from administering damaged vaccine. Studies have shown a lack of awareness of health workers regarding the use and interpretation of a VVM. The current study, undertaken among the caregivers of children who were immunized, showed that this lack of information about the VVM also exists among the caregivers. This deficiency in knowledge, both in the health workers and the caregivers, can affect the health of the child and needs urgent attention.
Verma, Ramesh; Khanna, Pardeep; Chawla, Suraj
Polio is a communicable disease caused by poliovirus that may attack nerve cells of the brain and spinal cord. The victims develop neurological complications, likes stiffness of the neck, muscular weakness, or paralysis of one or more limbs. In severe cases, it may be fatal due to respiratory paralysis. The world has seen tremendous gains in polio eradication over the past year. India and Nigeria saw a reduction in cases of almost 95% from 2009 to 2010, and cases of wild poliovirus type 3 (WPV3) fell by 92% globally over the same period. In fact, no case has been reported in India since February 2011, such that India may be on the verge of eradicating polio. Nevertheless, polio control experts are particularly worried about Vaccine-Derived Poliovirus (VDPV). Global surveillance efforts picked up 430 cases of VDPV from several countries between July 2009 and March 2011. In India, 7 cases of VDPV were reported during the year 2011. As long as OPV is used, virologists say that the world is at risk of VDPV causing polio in unprotected children. Achieving a polio-free world will require the "cessation of all OPV" and with it the elimination of the risk of vaccine-associated paralytic polio (VAPP) or VDPV infections. To this effect, in 2011 the Global Polio Eradication Initiative (GPEI) will produce and develop a new roadmap for VDPV Elimination. Several countries have shifted from all OPV to sequential OPV-IPV schedules and all-IPV schedules with elimination of live poliovirus. IPV will be indispensable in the post-eradication era when use of OPV has to stop but "vaccination against polio" cannot stop. IPV offers complete individual protection and has been considered as an additional tool at present for those who can afford the vaccine, and since we are nearing the eradication of polio, it is time to shift from OPV to sequential OPV-IPV schedule in India. Such a strategy will avoid inevitable problems with VAPP.
Full Text Available Intranasal vaccination is more potent than parenteral injection for the prevention of influenza. However, because the poor efficiency of antigen uptake across the nasal mucosa is a key issue, immunostimulatory adjuvants are essential for intranasal vaccines. The immunomodulator mannatide or polyactin (PA has been used for the clinical treatment of impaired immunity in China, but its adjuvant effect on an inactivated trivalent influenza vaccine (ITIV via intranasal vaccination is unclear. To explore the adjuvant effect of PA, an inactivated trivalent influenza virus with or without PA or MF59 was instilled intranasally once a week in BALB/c mice. Humoral immunity was assessed by both the ELISA and hemagglutination inhibition (HI methods using antigen-specific antibodies. Splenic lymphocyte proliferation and the IFN-γ level were measured to evaluate cell-mediated immunity. The post-vaccination serum HI antibody geometric mean titers (GMTs for the H1N1 and H3N2 strains, antigen-specific serum IgG and IgA GMTs, mucosal SIgA GMT, splenic lymphocyte proliferation, and IFN-γ were significantly increased in the high-dose PA-adjuvanted vaccine group. The seroconversion rate and the mucosal response for the H3N2 strain were significantly elevated after high-dose PA administration. These adjuvant effects of high-dose PA for the influenza vaccine were comparable with those of the MF59 adjuvant, and abnormal signs or pathological changes were not found in the evaluated organs. In conclusion, PA is a novel mucosal adjuvant for intranasal vaccination with the ITIV that has safe and effective mucosal adjuvanticity in mice and successfully induces both serum and mucosal antibody responses and a cell-mediated response.
Ma, Lei; Cai, Wei; Sun, Mingbo; Cun, Yina; Zhou, Jian; Liu, Jing; Hu, Wenzhu; Zhang, Xinwen; Song, Shaohui; Jiang, Shude; Liao, Guoyang
The live-attenuated oral polio vaccine (OPV) will be no longer used when wild poliovirus (WPV) eliminating in worldwide, according to GPEI (the Global Polio Eradication Initiative) Reports. It is planning to replace OPV by Sabin-based inactivated poliovirus vaccine (sIPV) in developing countries, with purpose of reducing of the economic burden and maintaining of the appropriate antibody levels in population. It studied serial fractional doses immunized by intradermal injection (ID) in rats, to reduce consume of antigen and financial burden, maintaining sufficient immunogenicity; Methods: Study groups were divided in 4 groups of dose gradient, which were one-tenth (1/10), one-fifth (1/5), one-third (1/3) and one-full dose (1/1), according to the volume of distribution taken from the same batch of vaccine (sIPV). Wistar rats were injected intradermally with the needle and syringe sing the mantoux technique taken once month for 3 times. It was used as positive control that intramuscular inoculation (IM) was injected with one-full dose (1/1) with same batch of sIPV. PBS was used as negative control. Blood samples were collected via tail vein. After 30 d with 3 round of immunization, it analyzed the changes of neutralization antibody titers in the each group by each immunization program end; Results: The results of seroconversion had positive correlation with different doses in ID groups. The higher concentration of D-antigen (D-Ag) could conduct higher seroconversion. Furthermore, different types of viruses had different seroconversion trend. It showed that the geometric mean titers (GMTs) of each fractional-dose ID groups increased by higher concentration of D-Ag, and it got significant lower than the full-dose IM group. At 90 th days of immunization, the GMTs for each poliovirus subtypes of fractional doses were almost higher than 1:8, implied that it could be meaning positive seroprotection titer for polio vaccine types, according to WHO suggestion; Conclusions
Full Text Available Enterovirus 71 (EV71 has caused epidemics of hand, foot and mouth diseases in Asia during the past decades and no vaccine is available. A formalin-inactivated EV71 candidate vaccine (EV71vac based on B4 subgenotype has previously been developed and found to elicit strong neutralizing antibody responses in mice and humans. In this study, we evaluated the long-term immunogenicity and safety of this EV71vac in a non-human primate model. Juvenile macaques were immunized at 0, 3 and 6 weeks either with 10 or 5 µg doses of EV71vac formulated with AlPO4 adjuvant, or PBS as control. During the 56 weeks of studies, no fever nor local redness and swelling at sites of injections was observed in the immunized macaques. After single immunization, 100% seroconversion based on 4-fold increased in neutralization titer (Nt was detected in EV71vac immunized monkeys but not PBS controls. A dose-dependent IgG antibody response was observed in monkeys receiving EV71vac immunization. The Nt of EV71vac immunized macaques had reached the peak after 3 vaccinations, then decreased gradually; however, the GMT of neutralizing antibody in the EV71vac immunized macaques were still above 100 at the end of the study. Correspondingly, both dose- and time-dependent interferon-γ and CD4+ T cell responses were detected in monkeys receiving EV71vac. Interestingly, similar to human responses, the dominant T cell epitopes of macaques were identified mainly in VP2 and VP3 regions. In addition, strong cross-neutralizing antibodies against most EV71 subgenotypes except some C2 and C4b strains, and Coxsackievirus A16 were observed. In summary, our results indicate that EV71vac elicits dose-dependent T-cell and antibody responses in macaques that could be a good animal model for evaluating the long-term immune responses elicited by EV71 vaccines.
Gu, Zhenqing; Dong, Jing; Wang, Jichun; Hou, Chengcai; Sun, Haifeng; Yang, Wenping; Bai, Juan; Jiang, Ping
A highly virulent and antigenic variant of pseudorabies virus (PRV) broke out in China at the end of 2011 and caused great economic loss in the pig industry. In this study, an infectious bacterial artificial chromosome (BAC) clone containing the full-length genome of the emerged variant PRV ZJ01 strain was generated. The BAC-derived viruses, vZJ01-GFPΔgE/gI (gE/gI deleted strain, and exhibiting green autofluorescence), vZJ01ΔgE/gI (gE/gI deleted strain), and vZJ01gE/gI-R (gE/gI revertant strain), showed similar in vitro growth to their parent strain. In pigs, inactivated vZJ01ΔgE/gI vaccine generated significantly high levels of neutralizing antibodies against ZJ01 compared with Bartha-K61 live vaccine (pvaccine group survived without exhibiting any clinical sings, but two of five animals exhibited central nervous signs in the Bartha-K61 group. Meanwhile, all the non-vaccinated control animals died at 7 days post-challenge. This indicates that the inactivated vZJ01ΔgE/gI vaccine is a promising vaccine candidate for controlling the variant strains of PRV now circulating in China. Copyright © 2014 Elsevier B.V. All rights reserved.
Tischner, H.; Huyuh, P.L.; Phan, P.N.; Bergmann, K.C.; Hoang, T.N.; Luther, P.; Nordheim, W.; Braeuniger, S.; Waldman, R.H.
Antibodies in nasal secretion and saliva were measured in 10 Macacus rhesus wich had been immunized orally with a 60 Co-gamma-inactivated influenza vaccine. Prior to immunization monkeys had no detectable antibodies against hemagglutinin (HA) and neuraminidase, resp. in sera or secretions. Oral immunization using intraoesophageal tubing, induced the occurrence of both antiobodies in pilocarpine-stimulated secretions within 28 days but not in sera. 6 monkeys reacted with increasing HA antibodies in nasal secretions and 10 monkeys with increasing neuraminidase antibodies. Salivary HA antibodies occurred in 8 of 10 and neuraminidase antibodies in 9 of 10 animals. In most cases antibodies occurred in both secretions simultaneously. These results demonstrate the stimulation of antibodies specific to influenza in the respiratory tract of monkeys after oral immunization with an inactivated vaccine, for the first time. (author)
Minor, Philip D
Poliomyelitis is caused by poliovirus, which is a positive strand non-enveloped virus that occurs in three distinct serotypes (1, 2, and 3). Infection is mainly by the fecal-oral route and can be confined to the gut by antibodies induced either by vaccine, previous infection or maternally acquired. Vaccines include the live attenuated strains developed by Sabin and the inactivated vaccines developed by Salk; the live attenuated vaccine (Oral Polio Vaccine or OPV) has been the main tool in the Global Program of Polio eradication of the World Health Organisation. Wild type 2 virus has not caused a case since 1999 and type 3 since 2012 and eradication seems near. However most infections are entirely silent so that sophisticated environmental surveillance may be needed to ensure that the virus has been eradicated, and the live vaccine can sometimes revert to virulent circulating forms under conditions that are not wholly understood. Cessation of vaccination is therefore an increasingly important issue and inactivated polio vaccine (IPV) is playing a larger part in the end game.
Migunov, A.I.; Yudin, I.V.; Bannikov, A.I.; Kuznetsov, O.K.
Inactivation of influenza virus by 60 Co-γ-rays in producing an influenza virus vaccine leads to yellowing of the pre-- paration and a decrease in its opalescence. The change in optic properties was only observed at a dose of 5 Gy and higher with sucrose and protein stabilizer simultaneosly present in the solution. It was established that the formation of stained compounds is the result of a radiochemical interaction between intermediate products of radiolysis of these components
Immunogenicity and Safety of a Trivalent Inactivated Influenza Vaccine in Children 6 Months to 17 Years of Age, Previously Vaccinated with an AS03-Adjuvanted A(H1N1)Pdm09 Vaccine: Two Open-label, Randomized Trials.
Vesikari, Timo; Richardus, Jan Hendrik; Berglund, Johan; Korhonen, Tiina; Flodmark, Carl-Erik; Lindstrand, Ann; Silfverdal, Sven Arne; Bambure, Vinod; Caplanusi, Adrian; Dieussaert, Ilse; Roy-Ghanta, Sumita; Vaughn, David W
During the influenza pandemic 2009-2010, an AS03-adjuvanted A(H1N1)pdm09 vaccine was used extensively in children 6 months of age and older, and during the 2010-2011 influenza season, the A(H1N1)pdm09 strain was included in the seasonal trivalent inactivated influenza vaccine (TIV) without adjuvant. We evaluated the immunogenicity and safety of TIV in children previously vaccinated with the AS03-adjuvanted A(H1N1)pdm09 vaccine. Healthy children were randomized (1:1) to receive TIV or a control vaccine. Children were aged 6 months to 9 years (n = 154) and adolescents 10-17 years (n = 77) when they received AS03-adjuvanted A(H1N1)pdm09 vaccine at least 6 months before study enrolment. Hemagglutination inhibition (HI) and neutralizing antibody responses against the A(H1N1)pdm09 strain were evaluated before (day 0) and at day 28 and month 6 after study vaccination. Reactogenicity was assessed during the 7 day postvaccination period, and safety was assessed for 6 months. At day 0, >93.9% of all children had HI titers ≥1:40 for the A(H1N1)pdm09 strain, which increased to 100% at both day 28 and month 6 in the TIV group. Between days 0 and 28, HI antibody geometric mean titers against A(H1N1)pdm09 increased by 9-fold and 4-fold in children 6 months to 9 years of age and 10-17 years of age, respectively. AS03-adjuvanted A(H1N1)pdm09 vaccine-induced robust immune responses in children that persisted into the next season, yet were still boosted by TIV containing A(H1N1)pdm09. The reactogenicity and safety profile of TIV did not appear compromised by prior receipt of AS03-adjuvanted A(H1N1)pdm09 vaccine.
Zaman, S; Carlsson, B; Jalil, F; Mellander, L; Van Wezel, A L; Böttiger, M; Hanson, L A
A new antigen-rich inactivated poliovirus vaccine (IPV) in ordinary (IPV1), double (IPV2) and quadruple (IPV4) antigen concentrations was given in 2 doses to 6 and 18 week old Pakistani infants. The immune responses to poliovirus types 1 and 3 were compared to those in infants given three doses of oral poliovirus vaccine (OPV) at 6, 12 and 18 weeks of age. Enzyme-linked immunosorbent assay, ELISA, was used to estimate IgG and IgA in serum and secretory IgA (SIgA) in saliva. Two to three years later, a follow-up of the serum antibody response was carried out in the same infants using a microneutralization test. Serum IgG antibody responses to poliovirus type 1 antigen after two doses of IPV1, IPV2 and IPV4 were not significantly higher than the response after three doses of OPV at 21 weeks of age (p greater than 0.05). The serum IgG responses to poliovirus type 3 were similar to those against type 1 in all the groups. Mean neutralizing antibody titres to poliovirus type 1 was significantly higher in the IPV2 group than the rest of the groups (p less than 0.01). For type 3, these titres were highest but not significantly, in the IPV4 group (p greater than 0.05). This study shows that two doses of a new antigen-rich IPV can give similar immediate serum antibody responses as OPV but higher late responses. SIgA antibodies in saliva were more efficiently induced by OPV after three doses than after 2 doses of IPV (p less than 0.05).
Seĭbil', V B; Malyshkina, L P; Khishtova, S N; Lesnikova, M V; Baryshnikova, A S; Konopleva, T N; Mnozhina, E G; Agafonova, T V; Vladimirova, L A
Study the state of collective immunity against poliomyelitis in 7 regions of Russia in the last 3 years. 2579 sera were studied for antibodies against poliomyelitis virus. Antibodies (AT) against 3 types of viruses were determined in neutralization reaction in RD cell culture, the state of collective immunity in the examined individuals was evaluated by the percent of individuals with AT against a type of poliovirus and geometric mean AT titer. The circulation of wild polioviruses was judged by the presence of strain specific AT against wild and vaccine viruses in the examined children (311 sera were studied). The indicators of collective immunity against poliomyelitis in both select examined regions and select age groups were generally high. The data obtained allow to make a conclusion that the quality of vaccine prophylaxis in the examined regions is good. Introduction of wild poliovirus type 1 from Tajikistan in 2010 caused disease in 7 residents of Russia whereas an epidemic that had affected more than 700 individuals emerged in Tajikistan. The studies carried out confirmed the necessity to continue qualitative poliomyelitis vaccine prophylaxis in the country despite the lack of circulation of wild polioviruses that can be introduced at any time.
Walz, Paul H; Riddell, Kay P; Newcomer, Benjamin W; Neill, John D; Falkenberg, Shollie M; Cortese, Victor S; Scruggs, Daniel W; Short, Thomas H
Bovine viral diarrhea virus (BVDV) is an important viral cause of reproductive disease, immune suppression and clinical disease in cattle. The objective of this study was to compare reproductive protection in cattle against the impacts of bovine viral diarrhea virus (BVDV) provided by three different multivalent vaccines containing inactivated BVDV. BVDV negative beef heifers and cows (n = 122) were randomly assigned to one of four groups. Groups A-C (n = 34/group) received two pre-breeding doses of one of three commercially available multivalent vaccines containing inactivated fractions of BVDV 1 and BVDV 2, and Group D (n = 20) served as negative control and received two doses of saline prior to breeding. Animals were bred, and following pregnancy diagnosis, 110 cattle [Group A (n = 31); Group B (n = 32); Group C (n = 31); Group D (n = 16)] were subjected to a 28-day exposure to cattle persistently infected (PI) with BVDV (1a, 1b and 2a). Of the 110 pregnancies, 6 pregnancies resulted in fetal resorption with no material for testing. From the resultant 104 pregnancies, BVDV transplacental infections were demonstrated in 73 pregnancies. The BVDV fetal infection rate (FI) was calculated at 13/30 (43%) for Group A cows, 27/29 (93%) for Group B cows, 18/30 (60%) for Group C cows, and 15/15 (100%) for Group D cows. Statistical differences were observed between groups with respect to post-vaccination antibody titers, presence and duration of viremia in pregnant cattle, and fetal infection rates in offspring from BVDV-exposed cows. Group A vaccination resulted in significant protection against BVDV infection as compared to all other groups based upon outcome measurements, while Group B vaccination did not differ in protection against BVDV infection from control Group D. Ability of inactivated BVDV vaccines to provide protection against BVDV fetal infection varies significantly among commercially available products; however, in this challenge
Full Text Available The red deer (Cervus elaphus is a relevant reservoir for Coxiella burnetii in Iberia. C. burnetii genotypes that infect red deer also infect humans and domestic animals. Integrated control approaches that target both domestic and wild ruminants are, therefore, required to reduce C. burnetii infection risks in Iberia, especially in wildlife–livestock–human interaction scenarios. The aim of this field experiment was to test the efficacy of an inactivated phase I vaccine [Inactivated phase I vaccine (IPIV; Coxevac®] when used to control C. burnetii shedding prevalence and burden in red deer as a tool to prevent transmission to livestock and humans. A semi-extensively bred red deer population in which C. burnetii is endemic was used as a model of the Iberian context. Around 75% of the reproductive hinds (>1 year old; N = 441 in the population were first vaccinated early in 2012 and were then revaccinated 3 weeks later; they were subsequently revaccinated biannually until January 2014. 75% of the yearling females left as replacement in 2012 and 2013 were vaccinated in June and revaccinated thereafter following the same protocol. 25% of the population, including the replacement females, was kept as a control group throughout the study. Changes in the humoral immune response after vaccination were estimated by analyzing sera collected at 10 different times between January 2011 and January 2015. The vaccinated and control hinds were surveyed at 2.5, 3.5, and 4.5 months after calving in 2012, 2013, and 2014 to collect vaginal swabs, milk, and feces. The presence and burden of C. burnetii DNA in swabs, milk, and feces was evaluated by means of real-time PCR. Vaccination induced high antibody prevalence and levels. The proportion of animals shedding C. burnetii in vaginal secretions and milk did not change over time in the vaccination group with respect to the control group. In contrast, there was a significant reduction in the proportion of
Kinsman, John; Stöven, Svenja; Elgh, Fredrik; Murillo, Pilar; Sulzner, Michael
All European Union (EU) and European Economic Area (EEA) Member States have pledged to ensure political commitment towards sustaining the region's poliomyelitis-free status and eliminating measles. However, there remain significant gaps between policy and practice in many countries. This article reports on an assessment conducted for the European Commission that aimed to support improvements in preparedness and response to poliomyelitis and measles in Europe. A documentary review was complemented by qualitative interviews with professionals working in International and EU agencies, and in at-risk or recently affected EU/EEA Member States (six each for poliomyelitis and measles). Twenty-six interviews were conducted on poliomyelitis and 24 on measles; the data were subjected to thematic analysis. Preliminary findings were then discussed at a Consensus Workshop with 22 of the interviewees and eight other experts. Generic or disease-specific plans exist in the participating countries and cross-border communications during outbreaks were generally reported as satisfactory. However, surveillance systems are of uneven quality, and clinical expertise for the two diseases is limited by a lack of experience. Serious breaches of protocol have recently been reported from companies producing poliomyelitis vaccines, and vaccine coverage rates for both diseases were also sub-optimal. A set of suggested good practices to address these and other challenges is presented. Poliomyelitis and measles should be brought fully onto the policy agendas of all EU/EEA Member States, and adequate resources provided to address them. Each country must abide by the relevant commitments that they have already made.
Maritsi, Despoina N; Coffin, Susan E; Argyri, Ioanna; Vartzelis, George; Spyridis, Nick; Tsolia, Maria N
To describe the immunogenicity and side effects of immunisation against hepatitis A virus (HAV) in JIA patients on methotrexate treatment, who have not been previously exposed to HAV. Case-control study performed in JIA patients and healthy controls matched on age and gender. The subjects received two doses of inactivated anti-HAV vaccine (720 mIU/ml) intramuscularly at 0 and 6 months. Seroconversion, seroprotection rates and anti-HAV-IgG titres were measured at 1, 7 and 18 months. Children were monitored for adverse events. 83 JIA patients and 76 controls were enrolled in the study. At one month, seroprotection rates were lower in children with, as compared to those without JIA (48.2% vs. 65%; p=0.05). At 7 and 18 months, rates of seroprotection rose significantly and were similar in both groups. The titre of anti-HAV-IgG was lower in children with JIA than healthy children at all time points (pVaccines were well tolerated. Two doses of inactivated HAV vaccine were well tolerated and immunogenic in most immunosuppressed children with JIA; however, a single dose of HAV vaccine was insufficient to induce seroprotection in half of the patients. Further studies are required to analyse the long-term immunity against HAV in this population and optimal HAV immunisation regimen.
Technology transfer of oil-in-water emulsion adjuvant manufacturing for pandemic influenza vaccine production in Romania: Preclinical evaluation of split virion inactivated H5N1 vaccine with adjuvant.
Stavaru, Crina; Onu, Adrian; Lupulescu, Emilia; Tucureanu, Catalin; Rasid, Orhan; Vlase, Ene; Coman, Cristin; Caras, Iuliana; Ghiorghisor, Alina; Berbecila, Laurentiu; Tofan, Vlad; Bowen, Richard A; Marlenee, Nicole; Hartwig, Airn; Bielefeldt-Ohmann, Helle; Baldwin, Susan L; Van Hoeven, Neal; Vedvick, Thomas S; Huynh, Chuong; O'Hara, Michael K; Noah, Diana L; Fox, Christopher B
Millions of seasonal and pandemic influenza vaccine doses containing oil-in-water emulsion adjuvant have been administered in order to enhance and broaden immune responses and to facilitate antigen sparing. Despite the enactment of a Global Action Plan for Influenza Vaccines and a multi-fold increase in production capabilities over the past 10 years, worldwide capacity for pandemic influenza vaccine production is still limited. In developing countries, where routine influenza vaccination is not fully established, additional measures are needed to ensure adequate supply of pandemic influenza vaccines without dependence on the shipment of aid from other, potentially impacted first-world countries. Adaptation of influenza vaccine and adjuvant technologies by developing country influenza vaccine manufacturers may enable antigen sparing and corresponding increases in global influenza vaccine coverage capacity. Following on previously described work involving the technology transfer of oil-in-water emulsion adjuvant manufacturing to a Romanian vaccine manufacturing institute, we herein describe the preclinical evaluation of inactivated split virion H5N1 influenza vaccine with emulsion adjuvant, including immunogenicity, protection from virus challenge, antigen sparing capacity, and safety. In parallel with the evaluation of the bioactivity of the tech-transferred adjuvant, we also describe the impact of concurrent antigen manufacturing optimization activities. Depending on the vaccine antigen source and manufacturing process, inclusion of adjuvant was shown to enhance and broaden functional antibody titers in mouse and rabbit models, promote protection from homologous virus challenge in ferrets, and facilitate antigen sparing. Besides scientific findings, the operational lessons learned are delineated in order to facilitate adaptation of adjuvant technologies by other developing country institutes to enhance global pandemic influenza preparedness.
Khan, Tila; Heffron, Connie L; High, Kevin P; Roberts, Paul C
Potent and safe adjuvants are needed to improve the efficacy of parenteral and mucosal vaccines. Cytokines, chemokines and growth factors have all proven to be effective immunomodulatory adjuvants when administered with a variety of antigens. We have previously evaluated the efficacy of membrane-anchored interleukins (IL) such as IL-2 and IL-4 co-presented as Cytokine-bearing Influenza Vaccines (CYT-IVACs) using a mouse model of influenza challenge. Here, we describe studies evaluating the parenteral and mucosal adjuvanticity of membrane-bound IL-12 and IL-23 CYT-IVACs in young adult mice. Mucosal immunization using IL-12 and IL-23 bearing whole influenza virus vaccine (WIV) was more effective at eliciting virus-specific nasal IgA and reducing viral lung burden following challenge compared to control WIV vaccinated animals. Both IL-12 and IL-23 bearing WIV elicited the highest anti-viral IgA levels in serum and nasal washes. This study highlights for the first time the mucosal adjuvant potential of IL-12 and IL-23 CYT-IVAC formulations in eliciting mucosal immune responses and reducing viral lung burden. The co-presentation of immunomodulators in direct context with viral antigen in whole inactivated viral vaccines may provide a means to significantly lower the dose of vaccine required for protection.
Safety and immunogenicity of inactivated poliovirus vaccine when given with measles-rubella combined vaccine and yellow fever vaccine and when given via different administration routes: a phase 4, randomised, non-inferiority trial in The Gambia.
Clarke, Ed; Saidu, Yauba; Adetifa, Jane U; Adigweme, Ikechukwu; Hydara, Mariama Badjie; Bashorun, Adedapo O; Moneke-Anyanwoke, Ngozi; Umesi, Ama; Roberts, Elishia; Cham, Pa Modou; Okoye, Michael E; Brown, Kevin E; Niedrig, Matthias; Chowdhury, Panchali Roy; Clemens, Ralf; Bandyopadhyay, Ananda S; Mueller, Jenny; Jeffries, David J; Kampmann, Beate
The introduction of the inactivated poliovirus vaccine (IPV) represents a crucial step in the polio eradication endgame. This trial examined the safety and immunogenicity of IPV given alongside the measles-rubella and yellow fever vaccines at 9 months and when given as a full or fractional dose using needle and syringe or disposable-syringe jet injector. We did a phase 4, randomised, non-inferiority trial at three periurban government clinics in west Gambia. Infants aged 9-10 months who had already received oral poliovirus vaccine were randomly assigned to receive the IPV, measles-rubella, and yellow fever vaccines, singularly or in combination. Separately, IPV was given as a full intramuscular or fractional intradermal dose by needle and syringe or disposable-syringe jet injector at a second visit. The primary outcomes were seroprevalence rates for poliovirus 4-6 weeks post-vaccination and the rate of seroconversion between baseline and post-vaccination serum samples for measles, rubella, and yellow fever; and the post-vaccination antibody titres generated against each component of the vaccines. We did a per-protocol analysis with a non-inferiority margin of 10% for poliovirus seroprevalence and measles, rubella, and yellow fever seroconversion, and (1/3) log2 for log2-transformed antibody titres. This trial is registered with ClinicalTrials.gov, number NCT01847872. Between July 10, 2013, and May 8, 2014, we assessed 1662 infants for eligibility, of whom 1504 were enrolled into one of seven groups for vaccine interference and one of four groups for fractional dosing and alternative route of administration. The rubella and yellow fever antibody titres were reduced by co-administration but the seroconversion rates achieved non-inferiority in both cases (rubella, -4·5% [95% CI -9·5 to -0·1]; yellow fever, 1·2% [-2·9 to 5·5]). Measles and poliovirus responses were unaffected (measles, 6·8% [95% CI -1·4 to 14·9]; poliovirus serotype 1, 1·6% [-6·7 to 4·7
A live-attenuated and an inactivated chimeric porcine circovirus (PCV)1-2 vaccine are both effective at inducing a humoral immune response and reducing PCV2 viremia and intrauterine infection in female swine of breeding age.
Hemann, Michelle; Beach, Nathan M; Meng, Xiang-Jin; Wang, Chong; Halbur, Patrick G; Opriessnig, Tanja
The objective of this pilot study was to determine the efficacy of inactivated (1 or 2 dose) and live-attenuated chimeric porcine circovirus (PCV)1-2 vaccines in sows using the PCV2-spiked semen model. Thirty-five sows were randomly divided into 6 groups: negative and positive controls, 1 dose inactivated PCV1-2 vaccine challenged (1-VAC-PCV2), 2 dose inactivated PCV1-2 vaccine challenged (2-VAC-PCV2), 1 dose live-attenuated PCV1-2 vaccine unchallenged (1-LIVE-VAC), and 1 dose live-attenuated PCV1-2 vaccine challenged (1-LIVE-VAC-PCV2). The inactivated PCV1-2 vaccine induced higher levels of PCV2-specific antibodies in dams. All vaccination strategies provided good protection against PCV2 viremia in dams, whereas the majority of the unvaccinated sows were viremic. Four of the 35 dams became pregnant: a negative control, a positive control, a 2-VAC-PCV2 sow, and a 1-LIVE-VAC-PCV2 sow. The PCV2 DNA was detected in 100%, 67%, and 29% of the fetuses obtained from the positive control, inactivated vaccinated, or live-attenuated vaccinated dams, respectively. The PCV2 antigen in hearts was only detectable in the positive control litter (23% of the fetuses). The PCV1-2 DNA was detected in 29% of the fetuses in the litter from the 1-LIVE-VAC-PCV2 dam. Under the conditions of this pilot study, both vaccines protected against PCV2 viremia in breeding age animals; however, vertical transmission was not prevented.
Cadorna-Carlos, Josefina B; Nolan, Terry; Borja-Tabora, Charissa Fay; Santos, Jaime; Montalban, M Cecilia; de Looze, Ferdinandus J; Eizenberg, Peter; Hall, Stephen; Dupuy, Martin; Hutagalung, Yanee; Pépin, Stéphanie; Saville, Melanie
Inactivated quadrivalent influenza vaccine (IIV4) containing two influenza A strains and one strain from each B lineage (Yamagata and Victoria) may offer broader protection against seasonal influenza than inactivated trivalent influenza vaccine (IIV3), containing a single B strain. This study examined the safety, immunogenicity, and lot consistency of an IIV4 candidate. This phase III, randomized, controlled, multicenter trial in children/adolescents (9 through 17 years) and adults (18 through 60 years) was conducted in Australia and in the Philippines in 2012. The study was double-blind for IIV4 lots and open-label for IIV4 vs IIV3. Children/adolescents were randomized 2:2:2:1 and adults 10:10:10:1 to receive one of three lots of IIV4 or licensed IIV3. Safety data were collected for up to 6 months post-vaccination. Hemagglutination inhibition and seroneutralization antibody titers were assessed pre-vaccination and 21 days post-vaccination. 1648 adults and 329 children/adolescents received IIV4, and 56 adults and 55 children/adolescents received IIV3. Solicited reactions, unsolicited adverse events, and serious adverse events were similar for IIV3 and IIV4 recipients in both age groups. Injection-site pain, headache, malaise, and myalgia were the most frequently reported solicited reactions, most of which were mild and resolved within 3 days. No vaccine-related serious adverse events or deaths were reported. Post-vaccination antibody responses, seroconversion rates, and seroprotection rates for the 3 strains common to both vaccines were comparable for IIV3 and IIV4 in both age groups. Antibody responses to IIV4 were equivalent among vaccine lots and comparable between age groups for each of the 4 strains. IIV4 met all European Medicines Agency immunogenicity criteria for adults for all 4 strains. In both age groups, IIV4 was well tolerated and caused no safety concerns, induced robust antibody responses to all 4 influenza strains, and met all EMA immunogenicity
Diaz, Clemente; Lin, Leyi; Martinez, Luis J; Eckels, Kenneth H; Campos, Maribel; Jarman, Richard G; De La Barrera, Rafael; Lepine, Edith; Toussaint, Jean-François; Febo, Irma; Innis, Bruce L; Thomas, Stephen J; Schmidt, Alexander C
The safety and immunogenicity of four adjuvanted formulations of an investigational tetravalent dengue purified inactivated vaccine (DPIV) were evaluated in a predominantly dengue-primed population in Puerto Rico. In this placebo-controlled, randomized, observer-blind, phase I trial, 100 healthy adults were randomized 1:1:1:1:1 to receive DPIV at Day (D)0 and D28 (1 μg per dengue virus [DENV] type 1-4 adjuvanted with either alum, AS01 E or AS03 B , or 4 μg per DENV type adjuvanted with alum) or saline placebo. Functional antibody responses were assessed using a microneutralization assay at D56, Month (M)7, and M13. All DPIV formulations were well tolerated and no safety signals were identified through M13. The M13 according-to-protocol (ATP) immunogenicity cohort included 83 participants. The ATP analysis of immunogenicity was performed only on the 78 subjects seropositive for ≥ 1 DENV type at baseline: 69 tetravalent, three trivalent, two bivalent, and four monovalent. In all DPIV groups, geometric mean antibody titers (GMTs) increased from D0 to D56 and waned modestly through M13, while remaining well above prevaccination levels. The 4 μg + alum and the AS01 E - and AS03 B -adjuvanted formulations were highly immunogenic, with M13-neutralizing antibody GMTs against all four DENV types above 1,000. M13/D0 GMT ratios were highest in the 1 μg + AS03 B group (ranging 3.2-3.7 depending on the DENV type). These results encourage continued clinical development of DPIV (ClinicalTrials.gov: NCT01702857).
Coadministration of Recombinant Adenovirus Expressing GM-CSF with Inactivated H5N1 Avian Influenza Vaccine Increased the Immune Responses and Protective Efficacy Against a Wild Bird Source of H5N1 Challenge.
Wang, Xiangwei; Wang, Xinglong; Jia, Yanqing; Wang, Chongyang; Tang, Qiuxia; Han, Qingsong; Xiao, Sa; Yang, Zengqi
Wild birds play a key role in the spread of avian influenza virus (AIV). There is a continual urgent requirement for AIV vaccines to address the ongoing genetic changes of AIV. In the current study, we trialed a novel AIV vaccine against the wild bird source of H5N1 type AIV with recombinant adenovirus expressing granulocyte monocyte colony-stimulating factor (GM-CSF) as an adjuvant. A total of 150-day-old commercial chicks, with AIV-maternal-derived antibody, were divided into 6 groups. The primary vaccination was performed at day 14 followed by a subsequent boosting and intramuscular challenge on day 28 and 42, respectively. Recombinant GM-CSF (rGM-CSF) expressed by adenovirus, named as rAd-GM-CSF, raised the hemagglutination inhibition (HI) titers (log 2 ) against AIV from 7.0 (vaccinate with inactivated vaccine alone) to 8.4 after booster immunization. Moreover, the rGM-CSF addition markedly increased the expression of interferon-γ, interleukin-4, and major histocompatibility complex-II in the lungs, compared with those immunized with inactivated vaccine alone on day 29, that is, 18 h post booster immunization. Following challenge, chicks inoculated with the inactivated AIV vaccine and rAd-GM-CSF together exhibited mild clinical signs and 62% survivals compared to 33% in the group immunized with inactivated AIV vaccine alone. Higher level of HI titers, immune related molecule expressions, and protection ratio demonstrates a good potential of rGM-CSF in improving humoral and cell mediated immune responses of inactivated AIV vaccines.
Chaple, Enrique Beldarraín
Poliomyelitis was introduced in Cuba in the late nineteenth century by American residents in Isla de Pinos. The first epidemics occurred in 1906 and 1909 and increased in intensity between 1930 and 1958. The scope of the paper is to reconstruct the history of the disease and its epidemics in Cuba prior to 1961, the first National Polio Vaccination Campaign (1962) and its results, as well as analyze the ongoing annual vaccination campaigns through to certified elimination of the disease (1994). The logical historical method was used and archival documents and statistics from the Ministry of Health on morbidity and mortality through 2000 were reviewed. Gross morbidity and mortality rates were calculated and interviews with key figures were conducted.
Nível de imunidade contra a poliomielite em um grupo de crianças vacinadas de acordo com o calendário oficial de imunização (São Paulo, Brasil Level of immunity to poliomyelitis in a group of children vaccinated according to the current official vaccination scheme (S. Paulo, Brazil
controled conditions at the Experimental Health Unit of the Escola Paulista de Medicina. The study showed that the administration of 2 doses of OPV resulted in poor seroresponses and was not sufficient for effective immunization of the infants to all three poliovirus types. Only the infant group which received a complete series of 3 vaccine doses exhibited an adequate level of immunity, as high as 75% of triple-immunes. The prevalence of antibodies to type 1, 2 and 3 polioviruses was 83%, 96% and 88%, respectively. If, however, the operational conditions observed in the health units of the city of S. Paulo and the low socio-economic level of the majority of the population are considered, it is expected that primary immunization based on 3 doses of OPV is inadequate in order to mantain the disease under effective control. It is advisable to increase the number of vaccine doses from three to five, in order to overcome the adverse effects upon routine OPV vaccination and assure a high level of immunity to poliomyelitis of our child population.
Onishchenko, G G; Ezhlova, E B; Mel'nikova, A A; Lazikova, G F; Demina, Iu V; Frolova, N V
Problem of emergence and spread of poliomyelitis in Russian Federation and neighboring states is examined. Measures taken in Russian Federation to prevent emergence of poliomyelitis cases caused by wild type virus are discussed, as well as treaties and agreements between Russia, Commonwealth of Independent States, Shanghai Cooperation Organization states regarding epidemiological control of poliomyelitis and acute flaccid paralysis. Measure planned by Federal Service for Surveillance for Protection of Consumers Rights and Human Welfare to prevent emergence of poliomyelitis and acute flaccid paralysis cases in Russian Federation and neighboring countries are presented.
Gauger, Phillip C; Vincent, Amy L; Loving, Crystal L; Lager, Kelly M; Janke, Bruce H; Kehrli, Marcus E; Roth, James A
Influenza is an economically important respiratory disease affecting swine world-wide with potential zoonotic implications. Genetic reassortment and drift has resulted in genetically and antigenically distinct swine influenza viruses (SIVs). Consequently, prevention of SIV infection is challenging due to the increased rate of genetic change and a potential lack of cross-protection between vaccine strains and circulating novel isolates. This report describes a vaccine-heterologous challenge model in which pigs were administered an inactivated H1N2 vaccine with a human-like (δ-cluster) H1 six and three weeks before challenge with H1 homosubtypic, heterologous 2009 pandemic H1N1. At necropsy, macroscopic and microscopic pneumonia scores were significantly higher in the vaccinated and challenged (Vx/Ch) group compared to non-vaccinated and challenged (NVx/Ch) pigs. The Vx/Ch group also demonstrated enhanced clinical disease and a significantly elevated pro-inflammatory cytokine profile in bronchoalveolar lavage fluid compared to the NVx/Ch group. In contrast, viral shedding and replication were significantly higher in NVx/Ch pigs although all challenged pigs, including Vx/Ch pigs, were shedding virus in nasal secretions. Hemagglutination inhibition (HI) and serum neutralizing (SN) antibodies were detected to the priming antigen in the Vx/Ch pigs but no measurable cross-reacting HI or SN antibodies were detected to pandemic H1N1 (pH1N1). Overall, these results suggest that inactivated SIV vaccines may potentiate clinical signs, inflammation and pneumonia following challenge with divergent homosubtypic viruses that do not share cross-reacting HI or SN antibodies. Published by Elsevier Ltd.
Motamedi-Sedeh, Farahnaz; Soleimanjahi, Hoorieh; Jalilian, Amir Reza; Mahravani, Homayoon; Shafaee, Kamalodin; Sotoodeh, Masood; Taherkarami, Hamdolah; Jairani, Faramarz
Foot-and-mouth disease virus (FMDV) causes a highly contagious disease in cloven-hoofed animals and is the most damaging disease of livestock worldwide, leading to great economic losses. The aim of this research was the inactivation of FMDV type O/IRN/1/2007 to produce a gamma ray-irradiated (GRI) vaccine in order to immunize mice and guinea pigs. In this research, the Iranian isolated FMDV type O/IRN/1/2007 was irradiated by gamma ray to prepare an inactivated whole virus antigen and formulated as a GRI vaccine with unaltered antigenic characteristics. Immune responses against this vaccine were evaluated on mice and guinea pigs. The comparison of the immune responses between the GRI vaccine and conventional vaccine did not show any significant difference in neutralizing antibody titer, memory spleen T lymphocytes or IFN-γ, IL-4, IL-2 and IL-10 concentrations (p > 0.05). In contrast, there were significant differences in all of the evaluated immune factors between the two vaccinated groups of mice and negative control mice (p GRI vaccines obtained were 6.28 and 7.07, respectively, which indicated the high potency of both vaccines. GRI vaccine is suitable for both routine vaccination and control of FMDV in emergency outbreaks.
Full Text Available Abstract Background The objective of the present study was to elucidate the humoral and cellular immune response mechanisms by which a reformulated inactivated chimeric PCV1-2 vaccine reduces the PCV2 viremia. Forty PCV2 seronegative 3-week-old pigs were randomly divided into the following four groups: vaccinated challenged (T01, vaccinated non-challenged (T02, non-vaccinated challenged (T03, and non-vaccinated non-challenged (T04 animals. The pigs in groups T01 and T02 were immunized with a reformulated inactivated chimeric PCV1-2 vaccine (Fostera™ PCV; Pfizer Animal Health administered as a 2.0 ml dose at 21 days of age. At 35 days of age (0 days post-challenge, the pigs in groups T01 and T03 were inoculated intranasally with 2 ml each of PCV2b. Results A reduction of PCV2 viremia coincided with the appearance of both PCV2-specific neutralizing antibodies (NA and interferon-γ-secreting cells (IFN-γ-SCs in the vaccinated animals. However, the presence of anti-PCV2 IgG antibodies did not correlate with the reduction of PCV2 viremia. Lymphocyte subset analysis indicated that the numbers of CD3+ and CD4+ cells increased in vaccinated animals but the numbers of CD4+ cells decreased transiently in non-vaccinated animals. The observation of a delayed type hypersensitivity response in only the vaccinated animals also supports a CD4+ cell-associated protective cellular immune response induced by the reformulated inactivated chimeric PCV1-2 vaccine. Conclusions The induction of PCV2-specific NA and IFN-γ-SCs, and CD4+ cells by the reformulated inactivated chimeric PCV1-2 vaccine is the important protective immune response leading to reduction of the PCV2 viremia and control of the PCV2 infection. To our knowledge this is the first demonstration of protective humoral and cellular immunity induced by the reformulated inactivated chimeric PCV1-2 vaccine and its effect on reduction of PCV2 viremia by vaccination.
Full Text Available The main strategy of the worldwide Program of Poliomyelitis Eradication is based on immunization with oral poliovirus vaccine and active epidemiological surveillance aimed to demonstrate the absence of wild poliovirus circulation. The specification of the surveillance in the program, reporting and investigation of certain syndrome – the acute flaccid paralysis - as a specific feature of surveillance of poliomyelitis, is a new experience both for clinicians and epidemiologists. Along with the achieved results, problems in conducting the active epidemiological surveillance in Serbia, applied measures, and suggestions for improving its quality were presented. This experience might help in implementing the active surveillance for some other diseases that could be prevented by vaccine immunization.
controlled studies. Vaccine 2012; 30:886–92. 11. Piedra PA, Gaglani MJ, Kozinetz CA, et al. Trivalent live attenuated intranasal influenza vaccine...120:e553–64. 12. Halloran ME, Piedra PA, Longini IM Jr, et al. Efficacy of trivalent, cold-adapted, influenza virus vaccine against influenza A (Fujian
Verdijk, Pauline; Rots, Nynke Y; van Oijen, Monique G C T; Oberste, M Steven; Boog, Claire J; Okayasu, Hiromasa; Sutter, Roland W; Bakker, Wilfried A M
An inactivated poliovirus vaccine (IPV) based on attenuated poliovirus strains (Sabin-1, -2 and -3) was developed for technology transfer to manufacturers in low- and middle income countries in the context of the Global Polio Eradication Initiative. Safety and immunogenicity of the Sabin-IPV was evaluated in a double-blind, randomized, controlled, phase I 'proof-of-concept' trial. Healthy male adults received a single intramuscular injection with Sabin-IPV, Sabin-IPV adjuvanted with aluminum hydroxide or conventional IPV. Virus-neutralizing titers against both Sabin and wild poliovirus strains were determined before and 28 days after vaccination. No vaccine-related serious adverse events were observed, and all local and systemic reactions were mild or moderate and transient. In all subjects, an increase in antibody titer for all types of poliovirus (both Sabin and wild strains) was observed 28 days after vaccination. Sabin-IPV and Sabin-IPV adjuvanted with aluminum hydroxide administered as a booster dose were equally immunogenic and safe as conventional IPV. EudraCTnr: 2010-024581-22, NCT01708720. Copyright © 2013 Elsevier Ltd. All rights reserved.
Full Text Available Since the mid-1980s, two lineages of influenza B viruses have been distinguished. These can co-circulate, limiting the protection provided by inactivated trivalent influenza vaccines (TIVs. This has prompted efforts to formulate quadrivalent influenza vaccines (QIVs, to enhance protection against circulating influenza B viruses. This review describes the results obtained from seven phase III clinical trials evaluating the immunogenicity, safety, and lot-to-lot consistency of a new quadrivalent split-virion influenza vaccine (Vaxigrip Tetra® formulated by adding a second B strain to the already licensed TIV. Since Vaxigrip Tetra was developed by means of a manufacturing process strictly related to that used for TIV, the data on the safety profile of TIV are considered supportive of that of Vaxigrip Tetra. The safety and immunogenicity of Vaxigrip Tetra were similar to those of the corresponding licensed TIV. Moreover, the new vaccine elicits a superior immune response towards the additional strain, without affecting immunogenicity towards the other three strains. Vaxigrip Tetra is well tolerated, has aroused no safety concerns, and is recommended for the active immunization of individuals aged ≥6 months. In addition, preliminary data confirm its immunogenicity and safety even in children aged 6–35 months and its immunogenicity in older subjects (aged 66–80 years.
Efficacy of single dose of a bivalent vaccine containing inactivated Newcastle disease virus and reassortant highly pathogenic avian influenza H5N1 virus against lethal HPAI and NDV infection in chickens.
Full Text Available Highly pathogenic avian influenza (HPAI and Newcastle disease (ND are 2 devastating diseases of poultry, which cause great economic losses to the poultry industry. In the present study, we developed a bivalent vaccine containing antigens of inactivated ND and reassortant HPAI H5N1 viruses as a candidate poultry vaccine, and we evaluated its immunogenicity and protective efficacy in specific pathogen-free chickens. The 6:2 reassortant H5N1 vaccine strain containing the surface genes of the A/Chicken/Korea/ES/2003(H5N1 virus was successfully generated by reverse genetics. A polybasic cleavage site of the hemagglutinin segment was replaced by a monobasic cleavage site. We characterized the reverse genetics-derived reassortant HPAI H5N1 clade 2.5 vaccine strain by evaluating its growth kinetics in eggs, minimum effective dose in chickens, and cross-clade immunogenicity against HPAI clade 1 and 2. The bivalent vaccine was prepared by emulsifying inactivated ND (La Sota strain and reassortant HPAI viruses with Montanide ISA 70 adjuvant. A single immunization with this vaccine induced high levels of hemagglutination-inhibiting antibody titers and protected chickens against a lethal challenge with the wild-type HPAI and ND viruses. Our results demonstrate that the bivalent, inactivated vaccine developed in this study is a promising approach for the control of both HPAI H5N1 and ND viral infections.
Wu, Chia-Ying; Lin, Yi-Wen; Kuo, Chia-Ho; Liu, Wan-Hsin; Tai, Hsiu-Fen; Pan, Chien-Hung; Chen, Yung-Tsung; Hsiao, Pei-Wen; Chan, Chi-Hsien; Chang, Ching-Chuan; Liu, Chung-Cheng; Chow, Yen-Hung; Chen, Juine-Ruey
Epidemics and outbreaks caused by infections of several subgenotypes of EV71 and other serotypes of coxsackie A viruses have raised serious public health concerns in the Asia-Pacific region. These concerns highlight the urgent need to develop a scalable manufacturing platform for producing an effective and sufficient quantity of vaccines against deadly enteroviruses. In this report, we present a platform for the large-scale production of a vaccine based on the inactivated EV71(E59-B4) virus. The viruses were produced in Vero cells in a 200 L bioreactor with serum-free medium, and the viral titer reached 10(7) TCID50/mL 10 days after infection when using an MOI of 10(-4). The EV71 virus particles were harvested and purified by sucrose density gradient centrifugation. Fractions containing viral particles were pooled based on ELISA and SDS-PAGE. TEM was used to characterize the morphologies of the viral particles. To evaluate the cross-protective efficacy of the EV71 vaccine, the pooled antigens were combined with squalene-based adjuvant (AddaVAX) or aluminum phosphate (AlPO4) and tested in human SCARB2 transgenic (Tg) mice. The Tg mice immunized with either the AddaVAX- or AlPO4-adjuvanted EV71 vaccine were fully protected from challenges by the subgenotype C2 and C4 viruses, and surviving animals did not show any degree of neurological paralysis symptoms or muscle damage. Vaccine treatments significantly reduced virus antigen presented in the central nervous system of Tg mice and alleviated the virus-associated inflammatory response. These results strongly suggest that this preparation results in an efficacious vaccine and that the microcarrier/bioreactor platform offers a superior alternative to the previously described roller-bottle system.
Safety and tolerability of a cell culture derived trivalent subunit inactivated influenza vaccine administered to healthy children and adolescents: A Phase III, randomized, multicenter, observer-blind study.
Nolan, Terry; Chotpitayasunondh, Tawee; Capeding, Maria Rosario; Carson, Simon; Senders, Shelly David; Jaehnig, Peter; de Rooij, Richard; Chandra, Richa
Cell culture-derived inactivated influenza vaccines (TIVc) are necessary for scale and predictability of production to meet global demand. This study compared the safety and tolerability of TIVc with an egg-derived trivalent influenza vaccine (TIVf) in 4-17 yearolds. A Phase 3 observer blind, multicenter study enrolled 2055 healthy participants randomized 2:1 to receive either TIVc or TIVf, respectively (1372 TIVc and 683 TIVf evaluable subjects). Participants received one dose each on Days 1 and 28 (4-8 year-olds not previously vaccinated [NPV]) or one dose on Day 1 (4-8 and 9-17 yearolds previously vaccinated [PV]). Solicited adverse events (AEs) occurring within 7 days after each vaccination were assessed; participants were followed up for 6 months after their last dose for safety. Most solicited and unsolicited AEs were mild to moderate with vaccine-related SAEs were reported. TIVc and TIVf were similar in percentages of participants reporting solicited reactions in 4-8 years NPV group after the 1st dose: local reactions, TIVc: 48%, TIVf: 43%; systemic reactions, TIVc: 34%, TIVf: 32%; percentages were lower following the 2nd dose in TIVc; local reactions: TIVc: 40%; TIVf: 43%; systemic reactions: TIVc: 21%; TIVf: 22%. In 4-17 years PV group, solicited reactions were lower following TIVf, local reactions: TIVc: 53%; TIVf: 43%; systemic reactions: TIVc: 37%, TIVf: 30%. Injection-site pain was the most common solicited reaction, and was similar following TIVc and TIVf in 4-8 yearolds (TIVc: 56%; TIVf: 55%), and lower following TIVf in 9-17 years group (TIVc: 52%; TIVf: 42%). Reporting of unsolicited AEs was similar for TIVc and TIVf across the two age groups. TIVc was well tolerated and had a safety and reactogenicity profile similar to that of TIVf in healthy 4-17 yearolds (NCT01857206). Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.
Halasa, Natasha B; Gerber, Michael A; Berry, Andrea A; Anderson, Edwin L; Winokur, Patricia; Keyserling, Harry; Eckard, Allison Ross; Hill, Heather; Wolff, Mark C; McNeal, Monica M; Edwards, Kathryn M; Bernstein, David I
Children 6 through 35 months of age are recommended to receive half the dose of influenza vaccine compared with older children and adults. This was a 6-site, randomized 2:1, double-blind study comparing full-dose (0.5 mL) trivalent inactivated influenza vaccine (TIV) with half-dose (0.25 mL) TIV in children 6 through 35 months of age. Children previously immunized with influenza vaccine (primed cohort) received 1 dose, and those with no previous influenza immunizations (naive cohort) received 2 doses of TIV. Local and systemic adverse events were recorded. Sera were collected before immunization and 1 month after last dose of TIV. Hemagglutination inhibition antibody testing was performed. Of the 243 subjects enrolled (32 primed, 211 naive), data for 232 were available for complete analysis. No significant differences in local or systemic reactions were observed. Few significant differences in immunogenicity to the 3 vaccine antigens were noted. The immune response to H1N1 was significantly higher in the full-dose group among primed subjects. In the naive cohort, the geometric mean titer for all 3 antigens after 2 doses of TIV were significantly higher in the 12 through 35 months compared with the 6 through 11 months age group. Our study confirms the safety of full-dose TIV given to children 6 through 35 months of age. An increase in antibody responses after full- versus half-dose TIV was not observed, except for H1N1 in the primed group. Larger studies are needed to clarify the potential for improved immunogenicity with higher vaccine doses. Recommending the same dose could simplify the production, storage, and administration of influenza vaccines.
Vaccine Adjuvants in Fish Vaccines Make a Difference: Comparing Three Adjuvants (Montanide ISA763A Oil, CpG/Poly I:C Combo and VHSV Glycoprotein Alone or in Combination Formulated with an Inactivated Whole Salmonid Alphavirus Antigen
Hanna L. Thim
Full Text Available Most commercial vaccines offered to the aquaculture industry include inactivated antigens (Ag formulated in oil adjuvants. Safety concerns are related to the use of oil adjuvants in multivalent vaccines for fish, since adverse side effects (e.g., adhesions can appear. Therefore, there is a request for vaccine formulations for which protection will be maintained or improved, while the risk of side effects is reduced. Here, by using an inactivated salmonid alphavirus (SAV as the test Ag, the combined use of two Toll-like receptor (TLR ligand adjuvants, CpG oligonucleotides (ODNs and poly I:C, as well as a genetic adjuvant consisting of a DNA plasmid vector expressing the viral haemorrhagic septicaemia virus (VHSV glycoprotein (G was explored. VHSV-G DNA vaccine was intramuscularly injected in combination with intraperitoneal injection of either SAV Ag alone or combined with the oil adjuvant, Montanide ISA763, or the CpG/polyI:C combo. Adjuvant formulations were evaluated for their ability to boost immune responses and induce protection against SAV in Atlantic salmon, following cohabitation challenge. It was observed that CpG/polyI:C-based formulations generated the highest neutralizing antibody titres (nAbs before challenge, which endured post challenge. nAb responses for VHSV G-DNA- and oil-adjuvanted formulations were marginal compared to the CpG/poly I:C treatment. Interestingly, heat-inactivated sera showed reduced nAb titres compared to their non-heated counterparts, which suggests a role of complement-mediated neutralization against SAV. Consistently elevated levels of innate antiviral immune genes in the CpG/polyI:C injected groups suggested a role of IFN-mediated responses. Co-delivery of the VHSV-G DNA construct with either CpG/polyI:C or oil-adjuvanted SAV vaccine generated higher CD4 responses in head kidney at 48 h compared to injection of this vector or SAV Ag alone. The results demonstrate that a combination of pattern recognizing
Yakovenko, M L; Gmyl, A P; Ivanova, O E; Eremeeva, T P; Ivanov, A P; Prostova, M A; Baykova, O Y; Isaeva, O V; Lipskaya, G Y; Shakaryan, A K; Kew, O M; Deshpande, J M; Agol, V I
A large outbreak of poliomyelitis, with 463 laboratory-confirmed and 47 polio-compatible cases, took place in 2010 in Tajikistan. Phylogenetic analysis of the viral VP1 gene suggested a single importation of wild poliovirus type 1 from India in late 2009, its further circulation in Tajikistan and expansion into neighbouring countries, namely Kazakhstan, Russia, Turkmenistan and Uzbekistan. Whole-genome sequencing of 14 isolates revealed recombination events with enterovirus C with cross-overs within the P2 region. Viruses with one class of recombinant genomes co-circulated with the parental virus, and representatives of both caused paralytic poliomyelitis. Serological analysis of 327 sera from acute flaccid paralysis cases as well as from patients with other diagnoses and from healthy people demonstrated inadequate immunity against polio in the years preceding the outbreak. Evidence was obtained suggesting that vaccination against poliomyelitis, in rare cases, may not prevent the disease. Factors contributing to the peculiarities of this outbreak are discussed. The outbreak emphasises the necessity of continued vaccination against polio and the need, at least in risk areas, of quality control of this vaccination through well planned serological surveillance.
Yishu Tang; Wenbo Ma; Chunxia Zhou; Dongmei Wang; Shuren Zhang
Background: Tumor-induced immunosuppression can impede tumor-specific immune responses and limit the effects of cancer immunotherapy. The aim of this study was to investigate the possible effects of sequential chemoimmunotherapeutic strategies to enhance antitumor immune responses. Methods: Using the E7-expressing tumor TC-1 as the tumor model, the treatment groups were divided into the following groups: (1) inactivated allogeneic leukocyte infusion (ALI), (2) ALI + MMC-inactivated TC-1 cell ...
Full Text Available While wild type polio has been nearly eradicated there will be a need to continue immunisation programmes for some time because of the possibility of re-emergence and the existence of long term excreters of poliovirus. All vaccines in current use depend on growth of virus and most of the non-replicating (inactivated vaccines involve wild type viruses known to cause poliomyelitis. The attenuated vaccine strains involved in the eradication programme have been used to develop new inactivated vaccines as production is thought safer. However it is known that the Sabin vaccine strains are genetically unstable and can revert to a virulent transmissible form. A possible solution to the need for virus growth would be to generate empty viral capsids by recombinant technology, but hitherto such particles are so unstable as to be unusable. We report here the genetic manipulation of the virus to generate stable empty capsids for all three serotypes. The particles are shown to be extremely stable and to generate high levels of protective antibodies in animal models.
... UNICEF, and supported by key partners including the Bill & Melinda Gates Foundation. This followed the certification of the eradication ... UNICEF, and supported by key partners including the Bill & Melinda Gates Foundation. This followed the certification of the eradication ...
Bakker, Wilfried A M; Thomassen, Yvonne E; van't Oever, Aart G; Westdijk, Janny; van Oijen, Monique G C T; Sundermann, Lars C; van't Veld, Peter; Sleeman, Eelco; van Nimwegen, Fred W; Hamidi, Ahd; Kersten, Gideon F A; van den Heuvel, Nico; Hendriks, Jan T; van der Pol, Leo A
Industrial-scale inactivated polio vaccine (IPV) production dates back to the 1960s when at the Rijks Instituut voor de Volksgezondheid (RIV) in Bilthoven a process was developed based on micro-carrier technology and primary monkey kidney cells. This technology was freely shared with several pharmaceutical companies and institutes worldwide. In this contribution, the history of one of the first cell-culture based large-scale biological production processes is summarized. Also, recent developments and the anticipated upcoming shift from regular IPV to Sabin-IPV are presented. Responding to a call by the World Health Organization (WHO) for new polio vaccines, the development of Sabin-IPV was continued, after demonstrating proof of principle in the 1990s, at the Netherlands Vaccine Institute (NVI). Development of Sabin-IPV plays an important role in the WHO polio eradication strategy as biocontainment will be critical in the post-OPV cessation period. The use of attenuated Sabin strains instead of wild-type Salk polio strains will provide additional safety during vaccine production. Initially, the Sabin-IPV production process will be based on the scale-down model of the current, and well-established, Salk-IPV process. In parallel to clinical trial material production, process development, optimization and formulation research is being carried out to further optimize the process and reduce cost per dose. Also, results will be shown from large-scale (to prepare for future technology transfer) generation of Master- and Working virus seedlots, and clinical trial material (for phase I studies) production. Finally, the planned technology transfer to vaccine manufacturers in low and middle-income countries is discussed. Copyright © 2011 Elsevier Ltd. All rights reserved.
Full Text Available Enterovirus 71 (EV71 has caused several epidemics of hand, foot and mouth diseases (HFMD in Asia. No effective EV71 vaccine is available. A randomized and open-label phase I clinical study registered with ClinicalTrials.gov #NCT01268787, aims to evaluate the safety, reactogenicity and immunogenicity of a formalin-inactivated EV71 vaccine candidate (EV71vac at 5- and 10-µg doses. In this study we report the cross-neutralizing antibody responses from each volunteer against different subgenotypes of EV71 and CVA16.Sixty eligible healthy adults were recruited and vaccinated. Blood samples were obtained on day 0, 21 and 42 and tested against B1, B4, B5, C2, C4A, C4B and CVA16 for cross-neutralizing antibody responses.The immunogenicity of both 5- and 10- µg doses were found to be very similar. Approximately 45% of the participants had 4-fold increase in Nt, but there was no further increase in Nt after the second dose. EV71vac induced very strong cross-neutralizing antibody responses in >85% of volunteers without pre-existing Nt against subgenotype B1, B5 and C4A. EV71vac elicited weak cross-neutralizing antibody responses (∼20% of participants against a C4B and Coxsackie virus A16. Over 90% of vaccinated volunteers did not develop cross-neutralizing antibody responses (Nt<8 against a C2 strain. EV71vac can boost and significantly enhance the neutralizing antibody responses in volunteers who already had pre-vaccination antibodies against EV71 and/or CVA16.EV71vac is efficient in eliciting cross-neutralizing antibody responses against EV71 subgenotypes B1, B4, B5, and C4A, and provides the rationale for its evaluation in phase II clinical trials.ClinicalTrials.gov NCT01268787.
Molodecky, Natalie A; Blake, Isobel M; O'Reilly, Kathleen M; Wadood, Mufti Zubair; Safdar, Rana M; Wesolowski, Amy; Buckee, Caroline O; Bandyopadhyay, Ananda S; Okayasu, Hiromasa; Grassly, Nicholas C
Pakistan currently provides a substantial challenge to global polio eradication, having contributed to 73% of reported poliomyelitis in 2015 and 54% in 2016. A better understanding of the risk factors and movement patterns that contribute to poliovirus transmission across Pakistan would support evidence-based planning for mass vaccination campaigns. We fit mixed-effects logistic regression models to routine surveillance data recording the presence of poliomyelitis associated with wild-type 1 poliovirus in districts of Pakistan over 6-month intervals between 2010 to 2016. To accurately capture the force of infection (FOI) between districts, we compared 6 models of population movement (adjacency, gravity, radiation, radiation based on population density, radiation based on travel times, and mobile-phone based). We used the best-fitting model (based on the Akaike Information Criterion [AIC]) to produce 6-month forecasts of poliomyelitis incidence. The odds of observing poliomyelitis decreased with improved routine or supplementary (campaign) immunisation coverage (multivariable odds ratio [OR] = 0.75, 95% confidence interval [CI] 0.67-0.84; and OR = 0.75, 95% CI 0.66-0.85, respectively, for each 10% increase in coverage) and increased with a higher rate of reporting non-polio acute flaccid paralysis (AFP) (OR = 1.13, 95% CI 1.02-1.26 for a 1-unit increase in non-polio AFP per 100,000 persons aged poliomyelitis, with the radiation model of movement providing the best fit to the data. Six-month forecasts of poliomyelitis incidence by district for 2013-2016 showed good predictive ability (area under the curve range: 0.76-0.98). However, although the best-fitting movement model (radiation) was a significant determinant of poliomyelitis incidence, it did not improve the predictive ability of the multivariable model. Overall, in Pakistan the risk of polio cases was predicted to reduce between July-December 2016 and January-June 2017. The accuracy of the model may be limited
Natalie A Molodecky
Full Text Available Pakistan currently provides a substantial challenge to global polio eradication, having contributed to 73% of reported poliomyelitis in 2015 and 54% in 2016. A better understanding of the risk factors and movement patterns that contribute to poliovirus transmission across Pakistan would support evidence-based planning for mass vaccination campaigns.We fit mixed-effects logistic regression models to routine surveillance data recording the presence of poliomyelitis associated with wild-type 1 poliovirus in districts of Pakistan over 6-month intervals between 2010 to 2016. To accurately capture the force of infection (FOI between districts, we compared 6 models of population movement (adjacency, gravity, radiation, radiation based on population density, radiation based on travel times, and mobile-phone based. We used the best-fitting model (based on the Akaike Information Criterion [AIC] to produce 6-month forecasts of poliomyelitis incidence. The odds of observing poliomyelitis decreased with improved routine or supplementary (campaign immunisation coverage (multivariable odds ratio [OR] = 0.75, 95% confidence interval [CI] 0.67-0.84; and OR = 0.75, 95% CI 0.66-0.85, respectively, for each 10% increase in coverage and increased with a higher rate of reporting non-polio acute flaccid paralysis (AFP (OR = 1.13, 95% CI 1.02-1.26 for a 1-unit increase in non-polio AFP per 100,000 persons aged <15 years. Estimated movement of poliovirus-infected individuals was associated with the incidence of poliomyelitis, with the radiation model of movement providing the best fit to the data. Six-month forecasts of poliomyelitis incidence by district for 2013-2016 showed good predictive ability (area under the curve range: 0.76-0.98. However, although the best-fitting movement model (radiation was a significant determinant of poliomyelitis incidence, it did not improve the predictive ability of the multivariable model. Overall, in Pakistan the risk of polio cases
Ulianova, Onega V.; Ulyanov, Sergey
Testing of prototypes of vaccines against extremely dangerous diseases, such as tularemia and brucellosis has been performed using speckle-microscopy. Changes of microcirculation caused by effect of toxins at applications of suspension of photoinactivated bacteria have been studied. Toxic properties of prototypes of vaccines against tularemia and brucellosis have been analyzed.
Lelie, P. N.; Reesink, H. W.; Grijm, R.; de Jong-van Manen, S. T.; Reerink-Brongers, E. E.
The effect of simultaneous administration of hepatitis B immune globulin on the antibody response to a low dose of heat-inactivated hepatitis B vaccine was investigated in 175 health care workers. Subjects were divided into four groups: Groups I and II received 3 monthly injections of a reduced dose
Sáez-Llorens, Xavier; Clemens, Ralf; Leroux-Roels, Geert; Jimeno, José; Clemens, Sue Ann Costa; Weldon, William C; Oberste, M Steven; Molina, Natanael; Bandyopadhyay, Ananda S
Following the proposed worldwide switch from trivalent oral poliovirus vaccine (tOPV) to bivalent types 1 and 3 OPV (bOPV) in 2016, inactivated poliovirus vaccine (IPV) will be the only source of protection against poliovirus type 2. With most countries opting for one dose of IPV in routine immunisation schedules during this transition because of cost and manufacturing constraints, optimisation of protection against all poliovirus types will be a priority of the global eradication programme. We assessed the immunogenicity and safety of a novel monovalent high-dose inactivated poliovirus type 2 vaccine (mIPV2HD) in infants. This observer-blind, comparative, randomised controlled trial was done in a single centre in Panama. We enrolled healthy infants who had not received any previous vaccination against poliovirus. Infants were randomly assigned (1:1) by computer-generated randomisation sequence to receive a single dose of either mIPV2HD or standard trivalent IPV given concurrently with a third dose of bOPV at 14 weeks of age. At 18 weeks, all infants were challenged with one dose of monovalent type 2 OPV (mOPV2). Primary endpoints were seroconversion and median antibody titres to type 2 poliovirus 4 weeks after vaccination with mIPV2HD or IPV; and safety (as determined by the proportion and nature of serious adverse events and important medical events for 8 weeks after vaccination). The primary immunogenicity analyses included all participants for whom a post-vaccination blood sample was available. All randomised participants were included in the safety analyses. This trial is registered with ClinicalTrials.gov, number NCT02111135. Between April 14 and May 9, 2014, 233 children were enrolled and randomly assigned to receive mIPV2HD (117 infants) or IPV (116 infants). 4 weeks after vaccination with mIPV2HD or IPV, seroconversion to poliovirus type 2 was recorded in 107 (93·0%, 95% CI 86·8-96·9) of 115 infants in the mIPV2HD group compared with 86 (74·8%, 65·8
Trallero, Gloria; Cabrerizo, María; Avellón, Ana
The Spanish acute flaccid paralysis surveillance network is coordinated by the National Poliovirus Laboratory (NPL), which, since 1998, carries out polioviruses (PV) and other enteroviruses detected characterization by cell culture and molecular techniques. A total of 110,725 (70046+40679) samples were studied between 1998-2012 and enteroviruses were detected in 8% of these. Among these enteroviruses 241 PV were characterized as PV Sabin-like, except samples belong to an imported poliomyelitis case, all of which were characterised as vaccine derived PV type 2. The NPL has carried out the serotyping and the intratypic differentiation of all the isolated PV in Spain of any syndrome. It is shown that wild PV has not circulated in our country during the 15 years studied and that has led to the signing of the Act of the "eradication of poliomyelitis in Spain" by WHO in 2001, and the /"certification of the eradication of wild PV free for European countries" on 21 June 2002. Currently only 3 countries have endemic transmission of wild PV (Pakistan, Afghanistan and Nigeria). Until a complete worldwide eradication, was achieved, Spain will actively continue to participate in the maintenance of the poliomyelitis eradication infrastructure by monitoring and vaccination as well as the wild PV containment plan to avoid the spread of wild PV.
Ivanova, O.E.; Bogdanov, M.V.; Kazantseva, V.A.; Gabrilevskaia, L.N.; Kodkind, G.K.H.
The study of ozone inactivation of enteroviruses in sewage showed the presence in sewage of suspensions of organic origin and bacterial flora to influence the rate of inactivation. The inactivation rate of poliomyelitis virus in sewage free from organic suspension and bacterial flora was significantly higher than that in sewage containing such suspension and bacterial flora. The inactivation rate of enteroviruses was found not to depend upon the protein and salt composition and pH of sewage or strain appurtenance of viruses. The inactivation rate of enteroviruses directly depended upon the dose of ozone and time of contact with it. Differences in the resistance of different types of poliomyelitis virus, ECHO and Coxsackie viruses to the effect of ozone are likely exist. These differences are manifested within the range of relatively small doses of ozone. E. coli is more resistant to ozone than entero-viruses. The results of laboratory studies were used to choose the regimen of sanitation of urban sewage to be used in technological cycles of industrial enterprises.
Sugaya, Norio; Shinjoh, Masayoshi; Kawakami, Chiharu; Yamaguchi, Yoshio; Yoshida, Makoto; Baba, Hiroaki; Ishikawa, Mayumi; Kono, Mio; Sekiguchi, Shinichiro; Kimiya, Takahisa; Mitamura, Keiko; Fujino, Motoko; Komiyama, Osamu; Yoshida, Naoko; Tsunematsu, Kenichiro; Narabayashi, Atsushi; Nakata, Yuji; Sato, Akihiro; Taguchi, Nobuhiko; Fujita, Hisayo; Toki, Machiko; Myokai, Michiko; Ookawara, Ichiro; Takahashi, Takao
The 2014/15 influenza season in Japan was characterised by predominant influenza A(H3N2) activity; 99% of influenza A viruses detected were A(H3N2). Subclade 3C.2a viruses were the major epidemic A(H3N2) viruses, and were genetically distinct from A/New York/39/2012(H3N2) of 2014/15 vaccine strain in Japan, which was classified as clade 3C.1. We assessed vaccine effectiveness (VE) of inactivated influenza vaccine (IIV) in children aged 6 months to 15 years by test-negative case–control design based on influenza rapid diagnostic test. Between November 2014 and March 2015, a total of 3,752 children were enrolled: 1,633 tested positive for influenza A and 42 for influenza B, and 2,077 tested negative. Adjusted VE was 38% (95% confidence intervals (CI): 28 to 46) against influenza virus infection overall, 37% (95% CI: 27 to 45) against influenza A, and 47% (95% CI: -2 to 73) against influenza B. However, IIV was not statistically significantly effective against influenza A in infants aged 6 to 11 months or adolescents aged 13 to 15 years. VE in preventing hospitalisation for influenza A infection was 55% (95% CI: 42 to 64). Trivalent IIV that included A/New York/39/2012(H3N2) was effective against drifted influenza A(H3N2) virus, although vaccine mismatch resulted in low VE. PMID:27784529
Live vaccinia-rabies virus recombinants, but not an inactivated rabies virus cell culture vaccine, protect B-lymphocyte-deficient A/WySnJ mice against rabies: considerations of recombinant defective poxviruses for rabies immunization of immunocompromised individuals.
Lodmell, Donald L; Esposito, Joseph J; Ewalt, Larry C
Presently, commercially available cell culture rabies vaccines for humans and animals consist of the five inactivated rabies virus proteins. The vaccines elicit a CD4+ helper T-cell response and a humoral B-cell response against the viral glycoprotein (G) resulting in the production of virus neutralizing antibody. Antibody against the viral nucleoprotein (N) is also present, but the mechanism(s) of its protection is unclear. HIV-infected individuals with low CD4+ T-lymphocyte counts and individuals undergoing treatment with immunosuppressive drugs have an impaired neutralizing antibody response after pre- and post-exposure immunization with rabies cell culture vaccines. Here we show the efficacy of live vaccinia-rabies virus recombinants, but not a cell culture vaccine consisting of inactivated rabies virus, to elicit elevated levels of neutralizing antibody in B-lymphocyte deficient A/WySnJ mice. The cell culture vaccine also failed to protect the mice, whereas a single immunization of a vaccinia recombinant expressing the rabies virus G or co-expressing G and N equally protected the mice up to 18 months after vaccination. The data suggest that recombinant poxviruses expressing the rabies virus G, in particular replication defective poxviruses such as canarypox or MVA vaccinia virus that undergo abortive replication in non-avian cells, or the attenuated vaccinia virus NYVAC, should be evaluated as rabies vaccines in immunocompromised individuals.
David, Shannon C; Lau, Josyane; Singleton, Eve V; Babb, Rachelle; Davies, Justin; Hirst, Timothy R; McColl, Shaun R; Paton, James C; Alsharifi, Mohammed
Gamma-irradiation, particularly an irradiation dose of 50kGy, has been utilised widely to sterilise highly pathogenic agents such as Ebola, Marburg Virus, and Avian Influenza H5N1. We have reported previously that intranasal vaccination with a gamma-irradiated Influenza A virus vaccine (γ-Flu) results in cross-protective immunity. Considering the possible inclusion of highly pathogenic Influenza strains in future clinical development of γ-Flu, an irradiation dose of 50kGy may be used to enhance vaccine safety beyond the internationally accepted Sterility Assurance Level (SAL). Thus, we investigated the effect of irradiation conditions, including high irradiation doses, on the immunogenicity of γ-Flu. Our data confirm that irradiation at low temperatures (using dry-ice) is associated with reduced damage to viral structure compared with irradiation at room temperature. In addition, a single intranasal vaccination with γ-Flu irradiated on dry-ice with either 25 or 50kGy induced seroconversion and provided complete protection against lethal Influenza A challenge. Considering that low temperature is expected to reduce the protein damage associated with exposure to high irradiation doses, we titrated the vaccine dose to verify the efficacy of 50kGy γ-Flu. Our data demonstrate that exposure to 50kGy on dry-ice is associated with limited effect on vaccine immunogenicity, apparent only when using very low vaccine doses. Overall, our data highlight the immunogenicity of influenza virus irradiated at 50kGy for induction of high titre antibody and cytotoxic T-cell responses. This suggests these conditions are suitable for development of γ-Flu vaccines based on highly pathogenic Influenza A viruses. Copyright © 2017 Elsevier Ltd. All rights reserved.
Romanenkova, N I; Bichurina, M A; Rosaeva, N R
Control of poliovirus circulation by study of material from patients with acute flaccid paralysis and contact individuals, from children of risk groups; molecular characteristics of isolated polioviruses; monitoring of circulation of polioviruses and nonpoliomyelitis enteroviruses in population and the environment. Isolation and study of polioviruses and nonpoliomyelitis enteroviruses from various sources was performed in accordance with WHO recommendations. Prolonged persistence and circulation of vaccine related strains of polioviruses in children is demonstrated. Enterovirus serotypes that circulate in the population and the environment more frequently are determined. CONCLUSION. Long term control of poliomyelitis and acute flaccid paralysis in combination with additional control variants in children from risk groups and objects of the environment allowed to obtain valuable data on poliovirus and nonpoliomyelitis enteroviruses circulation for the Program of eradication of poliomyelitis.
Yang, Lisheng; Liu, Yajing; Li, Shuxuan; Zhao, Huan; Lin, Qiaona; Yu, Hai; Huang, Xiumin; Zheng, Qingbing; Cheng, Tong; Xia, Ningshao
Hand, foot, and mouth disease (HFMD) is a highly contagious disease that mainly affects infants and children. Enterovirus 71 (EV71) and coxsackievirus A16 (CA16) are the major pathogens of HFMD. Two EV71 vaccines were recently licensed in China and the administration of the EV71 vaccines is believed to significantly reduce the number of HFMD-related severe or fatal cases. However, a monovalent EV71 vaccine cannot cross-protect against CA16 infection, this may result in that it cannot effectively control the overall HFMD epidemic. In this study, a chimeric EV71, whose VP1/210-225 epitope was replaced by that of CA16, was constructed using a reverse genetics technique to produce a candidate EV71/CA16 bivalent vaccine strain. The chimeric EV71 was infectious and showed similar growth characteristics as its parental strain. The replacement of the VP1/210-225 epitope did not significantly affect the antigenicity and immunogenicity of EV71. More importantly, the chimeric EV71 could induce protective immunity against both EV71 and CA16, and protect neonatal mice against either EV71 or CA16 lethal infections, the chimeric EV71 constructed in this study was shown to be a feasible and promising candidate bivalent vaccine against both EV71 and CA16. The construction of a chimeric enterovirus also provides an alternative platform for broad-spectrum HFMD vaccines development. Copyright © 2016 Elsevier Ltd. All rights reserved.
Clinical trial to evaluate safety and immunogenicity of an oral inactivated enterotoxigenic Escherichia coli prototype vaccine containing CFA/I overexpressing bacteria and recombinantly produced LTB/CTB hybrid protein.
Lundgren, A; Leach, S; Tobias, J; Carlin, N; Gustafsson, B; Jertborn, M; Bourgeois, L; Walker, R; Holmgren, J; Svennerholm, A-M
We have developed a new oral vaccine against enterotoxigenic Escherichia coli (ETEC) diarrhea containing killed recombinant E. coli bacteria expressing increased levels of ETEC colonization factors (CFs) and a recombinant protein (LCTBA), i.e. a hybrid between the binding subunits of E. coli heat labile toxin (LTB) and cholera toxin (CTB). We describe a randomized, comparator controlled, double-blind phase I trial in 60 adult Swedish volunteers of a prototype of this vaccine. The safety and immunogenicity of the prototype vaccine, containing LCTBA and an E. coli strain overexpressing the colonization factor CFA/I, was compared to a previously developed oral ETEC vaccine, consisting of CTB and inactivated wild type ETEC bacteria expressing CFA/I (reference vaccine). Groups of volunteers were given two oral doses of either the prototype or the reference vaccine; the prototype vaccine was administered at the same or a fourfold higher dosage than the reference vaccine. The prototype vaccine was found to be safe and equally well-tolerated as the reference vaccine at either dosage tested. The prototype vaccine induced mucosal IgA (fecal secretory IgA and intestine-derived IgA antibody secreting cell) responses to both LTB and CFA/I, as well as serum IgA and IgG antibody responses to LTB. Immunization with LCTBA resulted in about twofold higher mucosal and systemic IgA responses against LTB than a comparable dose of CTB. The higher dose of the prototype vaccine induced significantly higher fecal and systemic IgA responses to LTB and fecal IgA responses to CFA/I than the reference vaccine. These results demonstrate that CF over-expression and inclusion of the LCTBA hybrid protein in an oral inactivated ETEC vaccine does not change the safety profile when compared to a previous generation of such a vaccine and that the prototype vaccine induces significant dose dependent mucosal immune responses against CFA/I and LTB. Copyright © 2013 Elsevier Ltd. All rights reserved.
Drexler, Jan Felix; Grard, Gilda; Lukashev, Alexander N; Kozlovskaya, Liubov I; Böttcher, Sindy; Uslu, Gökhan; Reimerink, Johan; Gmyl, Anatoly P; Taty-Taty, Raphaël; Lekana-Douki, Sonia Etenna; Nkoghe, Dieudonné; Eis-Hübinger, Anna M; Diedrich, Sabine; Koopmans, Marion; Leroy, Eric M; Drosten, Christian
In 2010, a large outbreak of poliomyelitis with unusual 47% lethality occurred in Pointe Noire, Republic of Congo. Vaccine-mediated immunity against the outbreak virus was never investigated. A wild poliovirus 1 (WPV1) isolated from a fatal case (termed PV1-RC2010) showed a previously unknown combination of amino acid exchanges in critical antigenic site 2 (AgS2, VP1 capsid protein positions 221SAAL → 221PADL). These exchanges were also detected in an additional 11 WPV1 strains from fatal cases. PV1-RC2010 escaped neutralization by three different mAbs relevant for AgS2. Virus neutralization was tested in sera from fatal cases, who died before supplementary immunization (n = 24), Gabonese recipients of recent oral polio vaccination (n = 12), routinely vaccinated German medical students (n = 34), and German outpatients tested for antipoliovirus immunity (n = 17) on Vero, human rhabdomyosarcoma, and human epidermoid carcinoma 2 cells. Fatal poliomyelitis cases gave laboratory evidence of previous trivalent vaccination. Neutralizing antibody titers against PV1-RC2010 were significantly lower than those against the vaccine strain Sabin-1, two genetically distinct WPV1s isolated in 1965 and 2010 and two genetically distinct vaccine-derived PV strains. Of German vaccinees tested according to World Health Organization protocols, 15-29% were unprotected according to their neutralization titers (poliomyelitis eradication in populations with predominantly vaccine-derived immunity. Sustained vaccination coverage and clinical and environmental surveillance will be necessary.
Pyhälä, R; Kleemola, M; Kumpulainen, V; Vartiainen, E; Lappi, S; Pönkä, A; Cantell, K
Vaccination of adults (healthy female employees potentially capable of transmitting influenza to high-risk persons; n = 104) in autumn 1990 with a trivalent influenza virus vaccine containing B/Yamagata/16/88 induced a low antibody response to B/Finland/150/90, a recent variant of B/Victoria/2/87-like viruses, as compared with the antibody response to B/Finland/172/91, a current variant in the lineage of B/Yamagata/16/88-like viruses. Up to the end of the epidemic season, the antibody status declined but was still significantly better than before the vaccination. The results suggest that the vaccine strain was appropriate for the outbreak of 1990 to 1991 in Finland, but may provide unsatisfactory protection against B/Victoria/2/87-like viruses. Evidence is given that use of Madin-Darby canine kidney (MDCK)-grown virus as an antigen in the haemagglutination inhibition test (HI) may provide more reliable information about the protective antibodies than use of untreated or ether-treated egg-grown viruses. Significantly higher postvaccination and postepidemic antibody titres were recorded among subjects who exhibited the antibody before vaccination than among seronegative subjects. A significantly higher response rate among initially seronegative people than among seropositive people was recorded for antibody to B/Finland/150/90, but no clear evidence was obtained that the pre-existing antibody could have had a negative effect on the antibody production.
Rouphael, Nadine G; Paine, Michele; Mosley, Regina; Henry, Sebastien; McAllister, Devin V; Kalluri, Haripriya; Pewin, Winston; Frew, Paula M; Yu, Tianwei; Thornburg, Natalie J; Kabbani, Sarah; Lai, Lilin; Vassilieva, Elena V; Skountzou, Ioanna; Compans, Richard W; Mulligan, Mark J; Prausnitz, Mark R
Microneedle patches provide an alternative to conventional needle-and-syringe immunisation, and potentially offer improved immunogenicity, simplicity, cost-effectiveness, acceptability, and safety. We describe safety, immunogenicity, and acceptability of the first-in-man study on single, dissolvable microneedle patch vaccination against influenza. The TIV-MNP 2015 study was a randomised, partly blinded, placebo-controlled, phase 1, clinical trial at Emory University that enrolled non-pregnant, immunocompetent adults from Atlanta, GA, USA, who were aged 18-49 years, naive to the 2014-15 influenza vaccine, and did not have any significant dermatological disorders. Participants were randomly assigned (1:1:1:1) to four groups and received a single dose of inactivated influenza vaccine (fluvirin: 18 μg of haemagglutinin per H1N1 vaccine strain, 17 μg of haemagglutinin per H3N2 vaccine strain, and 15 μg of haemagglutinin per B vaccine strain) (1) by microneedle patch or (2) by intramuscular injection, or received (3) placebo by microneedle patch, all administered by an unmasked health-care worker; or received a single dose of (4) inactivated influenza vaccine by microneedle patch self-administered by study participants. A research pharmacist prepared the randomisation code using a computer-generated randomisation schedule with a block size of 4. Because of the nature of the study, participants were not masked to the type of vaccination method (ie, microneedle patch vs intramuscular injection). Primary safety outcome measures are the incidence of study product-related serious adverse events within 180 days, grade 3 solicited or unsolicited adverse events within 28 days, and solicited injection site and systemic reactogenicity on the day of study product administration through 7 days after administration, and secondary safety outcomes are new-onset chronic illnesses within 180 days and unsolicited adverse events within 28 days, all analysed by intention to treat
Hakim, Hana; Allison, Kim J; Van de Velde, Lee-Ann; Tang, Li; Sun, Yilun; Flynn, Patricia M; McCullers, Jonathan A
Approaches to improve the immune response of immunocompromised patients to influenza vaccination are needed. Children and young adults (3-21 years) with cancer or HIV infection were randomized to receive 2 doses of high-dose (HD) trivalent influenza vaccine (TIV) or of standard-dose (SD) TIV. Hemagglutination inhibition (HAI) antibody titers were measured against H1, H3, and B antigens after each dose and 9 months later. Seroconversion was defined as ≥4-fold rise in HAI titer comparing pre- and post-vaccine sera. Seroprotection was defined as a post-vaccine HAI titer ≥1:40. Reactogenicity events (RE) were solicited using a structured questionnaire 7 and 14 days after each dose of vaccine, and adverse events by medical record review for 21 days after each dose of vaccine. Eighty-five participants were enrolled in the study; 27 with leukemia, 17 with solid tumor (ST), and 41 with HIV. Recipients of HD TIV had significantly greater fold increase in HAI titers to B antigen in leukemia group and to H1 antigen in ST group compared to SD TIV recipients. This increase was not documented in HIV group. There were no differences in seroconversion or seroprotection between HD TIV and SD TIV in all groups. There was no difference in the percentage of solicited RE in recipients of HD TIV (54% after dose 1 and 38% after dose 2) compared to SD TIV (40% after dose 1 and 20% after dose 2, p=0.27 and 0.09 after dose 1 and 2, respectively). HD TIV was more immunogenic than SD TIV in children and young adults with leukemia or ST, but not with HIV. HD TIV was safe and well-tolerated in children and young adults with leukemia, ST, or HIV. Copyright © 2016 Elsevier Ltd. All rights reserved.
Whiteside, Theresa L.; Piazza, Paolo; Reiter, Amanda; Stanson, Joanna; Connolly, Nancy C.; Rinaldo, Charles R.; Riddler, Sharon A.
In preparation for a pilot clinical trial in patients with chronic human immunodeficiency virus type 1 (HIV-1) infection, a novel dendritic cell (DC)-based vaccine is being manufactured. The trial will test the hypothesis that isolated endogenous virus presented by DCs serves as a potent immunogen for activation of CD8+ and CD4+ T cells specific for a broad range of autologous HIV-1 antigens. Production of the vaccine under good manufacture practice conditions involves (i) autologous virus isolation; (ii) superinfection of CD4+ T cells with the virus; (iii) inactivation of the virus in CD4+ T cells, T-cell apoptosis, and coincubation of T cells with autologous DCs; and (iv) product testing and release. Endogenous virus was isolated from peripheral blood-derived CD4+ T cells of three HIV-1-positive subjects by coincubation with autologous OKT-3-stimulated CD4+ T cells. CD4+ T-cell supernatants were tested for p24 levels by enzyme-linked immunosorbent assay (>25 ng/ml) and for the 50% tissue culture infective doses (TCID50; which ranged from 4,642 to 46,416/ml on day 19 of culture). Autologous CD4+ T cells that were separated on immunobeads (>95% purity) and superinfected with virus-expressed p24 (28 to 54%) had TCID50 of >400/ml on days 5 to 10. Virus inactivation with psoralen (20 μg/ml) and UVB irradiation (312 nm) reduced the TCID50 of the supernatants from 199,986 to 11/ml (>99%). 7-Amino-actinomycin D-positive, annexin V-positive CD4+ T cells were fed to autologous DCs generated by using the Elutra cell separation system and the Aastrom system. Flow analysis showed that DC loading was complete in 24 h. On the basis of these translational results and experience with the generation of DCs from HIV-1-infected patients in a previous clinical trial, the Investigational New Drug application for clinical vaccination was submitted and approved by the FDA (application no. BB-IND-13137). PMID:19038780
Whiteside, Theresa L; Piazza, Paolo; Reiter, Amanda; Stanson, Joanna; Connolly, Nancy C; Rinaldo, Charles R; Riddler, Sharon A
In preparation for a pilot clinical trial in patients with chronic human immunodeficiency virus type 1 (HIV-1) infection, a novel dendritic cell (DC)-based vaccine is being manufactured. The trial will test the hypothesis that isolated endogenous virus presented by DCs serves as a potent immunogen for activation of CD8(+) and CD4(+) T cells specific for a broad range of autologous HIV-1 antigens. Production of the vaccine under good manufacture practice conditions involves (i) autologous virus isolation; (ii) superinfection of CD4(+) T cells with the virus; (iii) inactivation of the virus in CD4(+) T cells, T-cell apoptosis, and coincubation of T cells with autologous DCs; and (iv) product testing and release. Endogenous virus was isolated from peripheral blood-derived CD4(+) T cells of three HIV-1-positive subjects by coincubation with autologous OKT-3-stimulated CD4(+) T cells. CD4(+) T-cell supernatants were tested for p24 levels by enzyme-linked immunosorbent assay (>25 ng/ml) and for the 50% tissue culture infective doses (TCID(50); which ranged from 4,642 to 46,416/ml on day 19 of culture). Autologous CD4(+) T cells that were separated on immunobeads (>95% purity) and superinfected with virus-expressed p24 (28 to 54%) had TCID(50) of >400/ml on days 5 to 10. Virus inactivation with psoralen (20 microg/ml) and UVB irradiation (312 nm) reduced the TCID(50) of the supernatants from 199,986 to 11/ml (>99%). 7-Amino-actinomycin D-positive, annexin V-positive CD4(+) T cells were fed to autologous DCs generated by using the Elutra cell separation system and the Aastrom system. Flow analysis showed that DC loading was complete in 24 h. On the basis of these translational results and experience with the generation of DCs from HIV-1-infected patients in a previous clinical trial, the Investigational New Drug application for clinical vaccination was submitted and approved by the FDA (application no. BB-IND-13137).
Diop, Ousmane M; Burns, Cara C; Wassilak, Steven G; Kew, Olen M
In 1988, the World Health Assembly resolved to eradicate poliomyelitis worldwide. One of the main tools used in polio eradication efforts has been live, attenuated oral poliovirus vaccine (OPV), an inexpensive vaccine easily administered by trained volunteers. OPV might require several doses to induce immunity, but then it provides long-term protection against paralytic disease through durable humoral immunity. Rare cases of vaccine-associated paralytic poliomyelitis can occur among immunologically normal OPV recipients, their contacts, and persons who are immunodeficient. In addition, vaccine-derived polioviruses (VDPVs) can emerge in areas with low OPV coverage to cause polio outbreaks and can replicate for years in persons who have primary, B-cell immunodeficiencies. This report updates previous surveillance summaries and describes VDPVs detected worldwide during July 2012-December 2013. Those include a new circulating VDPV (cVDPV) outbreak identified in Pakistan in 2012, with spread to Afghanistan; an outbreak in Afghanistan previously identified in 2009 that continued into 2013; a new outbreak in Chad that spread to Cameroon, Niger, and northeastern Nigeria; and an outbreak that began in Somalia in 2008 that continued and spread to Kenya in 2013. A large outbreak in Nigeria that was identified in 2005 was nearly stopped by the end of 2013. Additionally, 10 newly identified persons in eight countries were found to excrete immunodeficiency-associated VDPVs (iVDPVs), and VDPVs were found among immunocompetent persons and environmental samples in 13 countries. Because the majority of VDPV isolates are type 2, the World Health Organization has developed a plan for coordinated worldwide replacement of trivalent OPV (tOPV) with bivalent OPV (bOPV; types 1 and 3) by 2016, preceded by introduction of at least 1 dose of inactivated poliovirus vaccine (IPV) containing all three poliovirus serotypes into routine immunization schedules worldwide to ensure high population
Collado-Vázquez, Susana; Carrillo, Jesús M; Águila-Maturana, Ana M
Poliomyelitis is an infectious disease whose initial symptoms are fever, fatigue, headaches, vomiting, a stiff neck and pains in the limbs. In many cases, the sequelae are irreversible paralysis and may result in death if there is bulbar or respiratory compromise. A set of symptoms, called post-polio syndrome, which appears years after the acute infection, are also described. To analyse the way poliomyelitis has been dealt with in literature, cinema and television. Film and television writers and directors have shown an interest in poliomyelitis and have portrayed it in a correct and realistic manner, both in fiction and in biographies or documentary-type works. Nemesis, Silver wattle, Leave her to heaven or The fall are some examples of literary works on the subject. Cinema has also portrayed polio all the way back to silent movies, with titles such as The woman in his house, The Silver Streak, Sister Kenny or The sessions. This disease and its sequelae have also been portrayed on television in series such as Hospital Central, Grey's anatomy, House M.D. or Amar en tiempos revueltos, and in TV films like El asunto, Eleanor and Franklin or Warm Springs. Poliomyelitis has been portrayed in literature, cinema and television in a realistic manner, showing its symptoms, sequelae, and the personal, familial and social impact of this disease.
Resik, Sonia; Tejeda, Alina; Mach, Ondrej; Fonseca, Magile; Diaz, Manuel; Alemany, Nilda; Garcia, Gloria; Hung, Lai Heng; Martinez, Yenisleydis; Sutter, Roland
The World Health Organization recommends that, as part of the new polio endgame, a dose of inactivated poliovirus vaccine (IPV) be introduced by the end of 2015 in all countries using only oral poliovirus vaccine (OPV). Administration of fractional dose (1/5th of full dose) IPV (fIPV) intradermally may reduce costs, but its administration is cumbersome with BCG needle and syringe. We evaluated performance of two newly developed intradermal-only jet injectors and compared the immune response induced by fIPV with that induced by full-dose IPV. Children between 12 and 20 months of age, who had previously received two doses of OPV, were enrolled in Camaguey, Cuba. Subjects received a single dose of IPV (either full-dose IPV intramuscularly with needle and syringe or fIPV intradermally administered with one of two new injectors or with BCG needle or a conventional needle-free injector). Serum was tested for presence of poliovirus neutralizing antibodies on day 0 (pre-IPV) and on days 3, 7 and 21 (post-vaccination). Complete data were available from 74.2% (728/981) subjects. Baseline median antibody titers were 713, 284, and 113 for poliovirus types 1, 2, and 3, respectively. Seroprevalence at study end were similar across the intervention groups (≥ 94.8%). The immune response induced with one new injector was similar to BCG needle and to the conventional injector; and superior to the other new injector. fIPV induced significantly lower boosting response compared to full-dose IPV. No safety concerns were identified. One of the two new injectors demonstrated its ability to streamline intradermal fIPV administration, however, further investigations are needed to assess the potential contribution of fIPV in the polio endgame plan. Copyright © 2014 Elsevier Ltd. All rights reserved.
Limia Sánchez, Aurora
Poliomyelitis was considered an important event for the public health since the end of XIX century when this disease became epidemic. As soon as vaccines were available member states of the World Health Organization (WHO) in the European Region started to implement vaccination programmes against polio with an important impact in the incidence in this disease. In May 1988, the World Health Assembly resolution for the global eradication of poliomyelitis was adopted and the mechanisms to oversee the progress in the different WHO Regions were established. This article briefly reviews the history of polio in the WHO European Region, the process for certification and maintenance, the strategies for eradication and the current situation in the European Region and globally. The European Region was certified polio-free in 2002. Nevertheless, there are still three endemic countries in the world, some others use live attenuated vaccines as well as countries in the Horn of Africa are recently suffering the reintroduction of wild poliovirus. Considering these circumstances, the risk of reintroduction of poliovirus and the generation of outbreaks in the European Region exists, therefore high vaccination coverage against polio and good quality surveillance systems are needed to be guaranteed in every member state.
Full Text Available Abstract Background Mycoplasma hyopneumoniae is the primary cause of enzootic pneumonia in pigs. Although vaccination is an important control tool, the results observed under field conditions are variable. This may be due to antigenic differences between the strains circulating in pig herds and the vaccine strain. This study compared the protective efficacy of four bacterins against challenge infection with a highly virulent field strain of M. hyopneumoniae. Seventy eight, one-week old piglets were randomly assigned to five treatment groups (A, B, C, D, E, 14 piglets each, and a negative control group (F consisting of 8 piglets. All pigs were injected at 1 (D7 and 4 weeks of age (D28, with 2 ml of either a placebo or a bacterin based on selected M. hyopneumoniae strains, namely A (F7.2C, B (F20.1L, C (B2V1W20 1A-F, D (J strain, E (placebo; positive control, F (placebo; negative control. At D56, all pigs except those of group F were challenged intratracheally with 7 ml culture medium containing 107 CCU/ml of M. hyopneumoniae strain F7.2C. All pigs were euthanized and necropsied at D84. The severity of coughing and pneumonia lesions were the main parameters. Immunofluorescence (IF testing, nested PCR testing of bronchoalveolar lavage (BAL fluid and serology for M. hyopneumoniae were also performed. Results The different bacterins only slightly improved clinical symptoms (average 0.38 in vaccinated groups vs. 0.45 in group E and histopathological lung lesions (average 3.20 in vaccinated groups vs. 3.45 in group E, but did not improve macroscopic lung lesions (score 4.30 vs. 4.03 in group E. None of the vaccines was significantly and/or consistently better or worse than the other ones. All bacterins evoked a serological response in the vaccinated animals. All pigs, except those from group F, were positive with nPCR in BAL fluid at D84. Conclusion The bacterins did not induce a clear overall protection against challenge infection, and there were no
Villarreal, Iris; Vranckx, Katleen; Calus, Dries; Pasmans, Frank; Haesebrouck, Freddy; Maes, Dominiek
Mycoplasma hyopneumoniae is the primary cause of enzootic pneumonia in pigs. Although vaccination is an important control tool, the results observed under field conditions are variable. This may be due to antigenic differences between the strains circulating in pig herds and the vaccine strain. This study compared the protective efficacy of four bacterins against challenge infection with a highly virulent field strain of M. hyopneumoniae. Seventy eight, one-week old piglets were randomly assigned to five treatment groups (A, B, C, D, E), 14 piglets each, and a negative control group (F) consisting of 8 piglets. All pigs were injected at 1 (D7) and 4 weeks of age (D28), with 2 ml of either a placebo or a bacterin based on selected M. hyopneumoniae strains, namely A (F7.2C), B (F20.1L), C (B2V1W20 1A-F), D (J strain), E (placebo; positive control), F (placebo; negative control). At D56, all pigs except those of group F were challenged intratracheally with 7 ml culture medium containing 107 CCU/ml of M. hyopneumoniae strain F7.2C. All pigs were euthanized and necropsied at D84. The severity of coughing and pneumonia lesions were the main parameters. Immunofluorescence (IF) testing, nested PCR testing of bronchoalveolar lavage (BAL) fluid and serology for M. hyopneumoniae were also performed. The different bacterins only slightly improved clinical symptoms (average 0.38 in vaccinated groups vs. 0.45 in group E) and histopathological lung lesions (average 3.20 in vaccinated groups vs. 3.45 in group E), but did not improve macroscopic lung lesions (score 4.30 vs. 4.03 in group E). None of the vaccines was significantly and/or consistently better or worse than the other ones. All bacterins evoked a serological response in the vaccinated animals. All pigs, except those from group F, were positive with nPCR in BAL fluid at D84. The bacterins did not induce a clear overall protection against challenge infection, and there were no significant differences in protective
Lewis, Ian; Ottosen, Ann; Rubin, Jennifer; Blanc, Diana Chang; Zipursky, Simona; Wootton, Emily
A total of 105 countries have introduced IPV as of September 2016 of which 85 have procured the vaccine through UNICEF. The Global Eradication and Endgame Strategic Plan 2013-2018 called for the rapid introduction of at least one dose of IPV into routine immunization schedules in 126 all OPV-using countries by the end of 2015. At the time of initiating the procurement process, demand was estimated based on global modeling rather than individual country indications. In its capacity as procurement agency for the Global Polio Eradication Initiative and Gavi, the Vaccine Alliance, UNICEF set out to secure access to IPV supply for around 100 countries. Based on offers received, sufficient supply was awarded to two manufacturers to meet projected routine requirements. However, due to technical issues scaling up vaccine production and an unforecasted demand for IPV use in campaigns to interrupt wild polio virus and to control type 2 vaccine derived polio virus outbreaks, IPV supplies are severely constrained. Activities to stretch supplies and to suppress demand have been ongoing since 2014, including delaying IPV introduction in countries where risks of type 2 reintroduction are lower, implementing the multi-dose vial policy, and encouraging the use of fractional dose delivered intradermally. Despite these efforts, there is still insufficient IPV supply to meet demand. The impact of the supply situation on IPV introduction timelines in countries are the focus of this article, and based on lessons learned with the IPV introductions, it is recommended for future health programs with accelerated scale up of programs, to take a cautious approach on supply commitments, putting in place clear allocation criteria in case of shortages or delays and establishing a communication strategy vis a vis beneficiaries. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.
Ottosen, Ann; Rubin, Jennifer; Blanc, Diana Chang; Zipursky, Simona; Wootton, Emily
Abstract A total of 105 countries have introduced IPV as of September 2016 of which 85 have procured the vaccine through UNICEF. The Global Eradication and Endgame Strategic Plan 2013-2018 called for the rapid introduction of at least one dose of IPV into routine immunization schedules in 126 all OPV-using countries by the end of 2015. At the time of initiating the procurement process, demand was estimated based on global modeling rather than individual country indications. In its capacity as procurement agency for the Global Polio Eradication Initiative and Gavi, the Vaccine Alliance, UNICEF set out to secure access to IPV supply for around 100 countries. Based on offers received, sufficient supply was awarded to two manufacturers to meet projected routine requirements. However, due to technical issues scaling up vaccine production and an unforecasted demand for IPV use in campaigns to interrupt wild polio virus and to control type 2 vaccine derived polio virus outbreaks, IPV supplies are severely constrained. Activities to stretch supplies and to suppress demand have been ongoing since 2014, including delaying IPV introduction in countries where risks of type 2 reintroduction are lower, implementing the multi-dose vial policy, and encouraging the use of fractional dose delivered intradermally. Despite these efforts, there is still insufficient IPV supply to meet demand. The impact of the supply situation on IPV introduction timelines in countries are the focus of this article, and based on lessons learned with the IPV introductions, it is recommended for future health programs with accelerated scale up of programs, to take a cautious approach on supply commitments, putting in place clear allocation criteria in case of shortages or delays and establishing a communication strategy vis a vis beneficiaries. PMID:28838159
VASHISHTHA, Vipin; NAVEEN, Thacker
More than two decade-old Global Polio Eradication Initiative (GPEI) has finally tasted success and wild poliovirus is now on the verge of eradication. The pre-eradication era was full of challenges and a great learning experience for all those involved with this tedious process. Many new phenomena emerged and new information about poliovirus learned during this campaign. Many new developments such as vaccine-derived polioviruses (VDPVs) were not anticipated and resulted in serious thinking re...
Kilany, Walid H; Safwat, Marwa; Mohammed, Samy M; Salim, Abdullah; Fasina, Folorunso Oludayo; Fasanmi, Olubunmi G; Shalaby, Azhar G; Dauphin, Gwenaelle; Hassan, Mohammed K; Lubroth, Juan; Jobre, Yilma M
In Egypt, ducks kept for commercial purposes constitute the second highest poultry population, at 150 million ducks/year. Hence, ducks play an important role in the introduction and transmission of avian influenza (AI) in the Egyptian poultry population. Attempts to control outbreaks include the use of vaccines, which have varying levels of efficacy and failure. To date, the effects of vaccine efficacy has rarely been determined in ducks. In this study, we evaluated the protective efficacy of a live recombinant vector vaccine based on a turkey Herpes Virus (HVT) expressing the H5 gene from a clade 2.2 H5N1 HPAIV strain (A/Swan/Hungary/499/2006) (rHVT-H5) and a bivalent inactivated H5N1 vaccine prepared from clade 2.2.1 and 220.127.116.11 H5N1 seeds in Mulard ducks. A 0.3ml/dose subcutaneous injection of rHVT-H5 vaccine was administered to one-day-old ducklings (D1) and another 0.5ml/dose subcutaneous injection of the inactivated MEFLUVAC was administered at 7 days (D7). Four separate challenge experiments were conducted at Days 21, 28, 35 and 42, in which all the vaccinated ducks were challenged with 106EID50/duck of H5N1 HPAI virus (A/chicken/Egypt/128s/2012(H5N1) (clade 2.2.1) via intranasal inoculation. Maternal-derived antibody regression and post-vaccination antibody immune responses were monitored weekly. Ducks vaccinated at 21, 28, 35 and 42 days with the rHVT-H5 and MEFLUVAC vaccines were protected against mortality (80%, 80%, 90% and 90%) and (50%, 70%, 80% and 90%) respectively, against challenges with the H5N1 HPAI virus. The amount of viral shedding and shedding rates were lower in the rHVT-H5 vaccine groups than in the MEFLUVAC groups only in the first two challenge experiments. However, the non-vaccinated groups shed significantly more of the virus than the vaccinated groups. Both rHVT-H5 and MEFLUVAC provide early protection, and rHVT-H5 vaccine in particular provides protection against HPAI challenge.
Kiderman, A; Furst, A; Stewart, B; Greenbaum, E; Morag, A; Zakay-Rones, Z
Influenza is responsible for considerable morbidity not only among older people but in younger age groups as well. However, most large-scale anti-influenza vaccination campaigns are still aimed principally at the elderly using injectable vaccines. Until now there has been much less emphasis on targeting younger populations or using intra-nasal vaccines in mass anti-influenza immunisation programmes. To assess the immunogenicity of a new inactivated intra-nasal anti-influenza vaccine and to measure its effect on respiratory morbidity in a volunteer general practice population. A prospective, double-blind, placebo-controlled trial using the new vaccine was carried out over the winter of 1997-98 on 274 healthy patients aged 12-60 from three Israeli general practices, 182 in the vaccine group and 92 in the placebo group. Following vaccination the changes in the antigen levels and episodes of respiratory illness in the vaccine and placebo groups were measured. Protective antibody levels occurred after a single dose of vaccine [influenza H1N1, 41% immune pre-vaccination to 73% post-vaccination; influenza H3N2, 35-66%; influenza B, 27-64%]. Between January and March 1998, when influenza activity was at a peak in Israel, the average number of respiratory illness events in the vaccine group [14 events/100 subjects per month] was significantly less than in the placebo group [22 events/100 subjects per month]; similarly, the average number of respiratory illness days in the vaccine group over the same period [69 days/100 subjects per month] was significantly less than in the placebo group [117 days/100 subjects per month]. The new vaccine possessed significant immunogenicity and was associated with a significant reduction in respiratory morbidity among a group of healthy older children and adults. Since intra-nasal vaccines are simpler to administer and more acceptable to the public than injections the vaccine's potential for use in routine anti-influenza vaccination
Full Text Available Abstract Background Seasonal influenza imposes a substantial personal morbidity and societal cost burden. Vaccination is the major strategy for influenza prevention; however, because antigenically drifted influenza A and B viruses circulate annually, influenza vaccines must be updated to provide protection against the predicted prevalent strains for the next influenza season. The aim of this study was to assess the efficacy, safety, reactogenicity, and immunogenicity of a trivalent inactivated split virion influenza vaccine (TIV in healthy adults over two influenza seasons in the US. Methods The primary endpoint of this double-blind, randomized study was the average efficacy of TIV versus placebo for the prevention of vaccine-matched, culture-confirmed influenza (VMCCI across the 2005-2006 and 2006-2007 influenza seasons. Secondary endpoints included the prevention of laboratory-confirmed (defined by culture and/or serology influenza, as well as safety, reactogenicity, immunogenicity, and consistency between three consecutive vaccine lots. Participants were assessed actively during both influenza seasons, and nasopharyngeal swabs were collected for viral culture from individuals with influenza-like illness. Blood specimens were obtained for serology one month after vaccination and at the end of each influenza season's surveillance period. Results Although the point estimate for efficacy in the prevention of all laboratory-confirmed influenza was 63.2% (97.5% confidence interval [CI] lower bound of 48.2%, the point estimate for the primary endpoint, efficacy of TIV against VMCCI across both influenza seasons, was 46.3% with a 97.5% CI lower bound of 9.8%. This did not satisfy the pre-specified success criterion of a one-sided 97.5% CI lower bound of >35% for vaccine efficacy. The VMCCI attack rates were very low overall at 0.6% and 1.2% in the TIV and placebo groups, respectively. Apart from a mismatch for influenza B virus lineage in 2005
Sui, Jinyu; Yang, Dawei; Qiao, Chuanling; Xu, Huiyang; Xu, Bangfeng; Wu, Yunpu; Yang, Huanliang; Chen, Yan; Chen, Hualan
Eurasian avian-like H1N1 (EA H1N1) swine influenza viruses are prevalent in pigs in Europe and Asia, but occasionally cause human infection, which raises concern about their pandemic potential. Here, we produced a whole-virus inactivated vaccine with an EA H1N1 strain (A/swine/Guangxi/18/2011, SW/GX/18/11) and evaluated its efficacy against homologous H1N1 and heterologous H1N1 and H1N2 influenza viruses in mice. A strong humoral immune response, which we measured by hemagglutination inhibition (HI) and virus neutralization (VN), was induced in the vaccine-inoculated mice upon challenge. The inactivated SW/GX/18/11 vaccine provided complete protection against challenge with homologous SW/GX/18/11 virus in mice and provided effective protection against challenge with heterologous H1N1 and H1N2 viruses with distinctive genomic combinations. Our findings suggest that this EA H1N1 vaccine can provide protection against both homologous H1N1 and heterologous H1N1 or H1N2 virus infection. As such, it is an excellent vaccine candidate to prevent H1N1 swine influenza. Copyright © 2016 Elsevier Ltd. All rights reserved.
Mangal, Tara D; Aylward, R Bruce; Mwanza, Michael; Gasasira, Alex; Abanida, Emmanuel; Pate, Muhammed A; Grassly, Nicholas C
The completion of poliomyelitis eradication is a global emergency for public health. In 2012, more than 50% of the world's cases occurred in Nigeria following an unanticipated surge in incidence. We aimed to quantitatively analyse the key factors sustaining transmission of poliomyelitis in Nigeria and to calculate clinical efficacy estimates for the oral poliovirus vaccines (OPV) currently in use. We used acute flaccid paralysis (AFP) surveillance data from Nigeria collected between January, 2001, and December, 2012, to estimate the clinical efficacies of all four OPVs in use and combined this with vaccination coverage to estimate the effect of the introduction of monovalent and bivalent OPV on vaccine-induced serotype-specific population immunity. Vaccine efficacy was determined using a case-control study with CIs based on bootstrap resampling. Vaccine efficacy was also estimated separately for north and south Nigeria, by age of the children, and by year. Detailed 60-day follow-up data were collected from children with confirmed poliomyelitis and were used to assess correlates of vaccine status. We also quantitatively assessed the epidemiology of poliomyelitis and programme performance and considered the reasons for the high vaccine refusal rate along with risk factors for a given local government area reporting a case. Against serotype 1, both monovalent OPV (median 32.1%, 95% CI 26.1-38.1) and bivalent OPV (29.5%, 20.1-38.4) had higher clinical efficacy than trivalent OPV (19.4%, 16.1-22.8). Corresponding data for serotype 3 were 43.2% (23.1-61.1) and 23.8% (5.3-44.9) compared with 18.0% (14.1-22.1). Combined with increases in coverage, this factor has boosted population immunity in children younger than age 36 months to a record high (64-69% against serotypes 1 and 3). Vaccine efficacy in northern states was estimated to be significantly lower than in southern states (p≤0.05). The proportion of cases refusing vaccination decreased from 37-72% in 2008 to 21
The World Initiative for the Eradication of Poliomyelitis (IMEP), launched in 1988, is based on two strategies: mass vaccination with oral polio vaccine (OPV) and surveillance of acute flaccid paralysis (AFP). The disease incidence was reduced by 99%, but eradication, originally scheduled for 2000, has still not been reached in 2010, and four countries continue to be endemic (India, Pakistan, Afghanistan and Nigeria). The obstacles to eradication are the difficulty in reaching all children to be vaccinated, especially in areas of insecurity; the imperfections of OPV--irregular efficacy and genetic instability; and the limitations of surveillance in detecting only the paralytic form of the disease, which often remains asymptomatic. The repeated postponements of the ending of the initiative, which greatly increased the cost of IMEP, spark debate about the actual feasibility of eradication and justification to continue funding in a difficult global economic context, so the initiative remains without significant impact on indicators of the Millennium Goals for Development.
Shaw, Edward B.; Thelander, H. E.
Medical skills should be developed by the staffs of smaller hospitals for the differential study of patients with symptoms resembling those of poliomyelitis in order to provide the rudiments of care for the occasional patient with mild poliomyelitis, to recognize the indications which point to the necessity of superior technical assistance, and to decide when it is appropriate to move patients to better equipped centers. The impetuous acquisition of mechanical aids for the treatment of special problems will be effective in small communities only to the extent that this equipment is kept serviceable and is operated by persons of sufficient skill. Epidemic situations in a small community can be met only by mobilization of facilities under adequate direction and by integration of care with that provided by larger treatment centers. PMID:12978885
Van Alstine, Luke W; Gunn, Paul W; Schroeder, Darrell R; Hanson, Andrew C; Sorenson, Eric J; Martin, David P
Poliomyelitis is a viral infectious disease caused by 1 of the 3 strains of poliovirus. The World Health Organization launched an eradication campaign in 1988. Although the number of cases of poliomyelitis has drastically declined, eradication has not yet been achieved, and there are a substantial number of survivors of the disease. Survivors of poliomyelitis present a unique set of challenges to the anesthesiologist. The scientific literature regarding the anesthetic management of survivors of poliomyelitis, however, is limited and primarily experiential in nature. Using a retrospective, matched cohort study, we sought to more precisely characterize the anesthetic implications of poliomyelitis and to determine what risks, if any, may be present for patients with a history of the disease. Using the Mayo Clinic Life Sciences System Data Discovery and Query Builder, study subjects were identified as those with a history of paralytic poliomyelitis who had undergone major surgery at Mayo Clinic Rochester between 2005 and 2009. For each case, 2 sex- and age-matched controls that underwent the same surgical procedure during the study period were randomly selected from a pool of possible controls. Medical records were manually interrogated with respect to demographic variables, comorbid conditions, operative and anesthetic course, and postoperative course. We analyzed 100 cases with 2:1 matched controls and found that the peri- and postoperative courses were very similar for both groups of patients. Pain scores, postanesthesia care unit admission, length of postanesthesia care unit stay, intensive care unit admission, length of intensive care unit stay, and initial extubation location were not significantly different between the 2 groups. Looking at pulmonary complications in our primary outcome, there was no significant difference between the 2 groups (17% vs 14% for polio versus control, respectively; conditional logistic regression odds ratio = 1.5; 95% confidence
Claudio Andre Barbosa de Lira
Full Text Available Poliomyelitis is an acute and infectious viral disease, transmitted primarily through oral-fecal contact or directly, person to person. Approximately 90% of the individuals infected by the polio virus do not present symptoms; however, the affected individuals can show a variety of symptoms if the virus reaches the bloodstream. In up to 2% of cases, the virus reaches the central nervous system preferably infecting and destroying the motor neurons, resulting in muscular weakness and acute flaccid paralysis. Despite the expressive reduction in the number of cases, many people live with the consequences of the acute illness, thus representing a burden to the public healthcare systems. Many of these people present new manifestations as signs and symptoms that are called post-polio syndrome. It can be defined and characterized by new neuromuscular symptoms, which occur at least 15 years after a period of clinical and functional stability in patients with previous history of symptomatic poliomyelitis. The signs and symptoms characterizing the post-polio syndrome include new muscular weakness, muscular fatigue and atrophy, pain in joints and muscles, sleep disorders, intolerance to cold, respiratory and swallowing difficulties, and recent weight gain. Therefore, the aim of this review is to present the physiological changes caused by the new manifestation of symptoms in individuals with poliomyelitis.
month through 14 years, constituting 109.4% of planned coverage. Since that year, no deaths from polio have been recorded (there were ten cases between 1963 and 1989) and WHO/PAHO certified polio elimination in Cuba in 1994. Cuba controlled polio with effective vaccination strategies and appropriate epidemiological measures, in the context of social, financial and political support. KEYWORDS History, poliomyelitis, epidemiology, disease control, vaccination, Sabin vaccine, Cuba.
O. A. Shamsutdinova
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
Few studies have been published in the literature regarding fractures of limbs in patients with poliomyelitis. We have conducted a retrospective study from 1992 to 2004 in order to present our data on fractures of lower limbs in adult patients with residua of poliomyelitis. During the thirteen-year period under study, only eight ...
Selinger, Christian; McCarthy, Kevin A.; Eckhoff, Philip A.; Chabot-Couture, Guillaume
The oral polio vaccine (OPV) contains live-attenuated polioviruses that induce immunity by causing low virulence infections in vaccine recipients and their close contacts. Widespread immunization with OPV has reduced the annual global burden of paralytic poliomyelitis by a factor of 10,000 or more and has driven wild poliovirus (WPV) to the brink of eradication. However, in instances that have so far been rare, OPV can paralyze vaccine recipients and generate vaccine-derived polio outbreaks. To complete polio eradication, OPV use should eventually cease, but doing so will leave a growing population fully susceptible to infection. If poliovirus is reintroduced after OPV cessation, under what conditions will OPV vaccination be required to interrupt transmission? Can conditions exist in which OPV and WPV reintroduction present similar risks of transmission? To answer these questions, we built a multi-scale mathematical model of infection and transmission calibrated to data from clinical trials and field epidemiology studies. At the within-host level, the model describes the effects of vaccination and waning immunity on shedding and oral susceptibility to infection. At the between-host level, the model emulates the interaction of shedding and oral susceptibility with sanitation and person-to-person contact patterns to determine the transmission rate in communities. Our results show that inactivated polio vaccine (IPV) is sufficient to prevent outbreaks in low transmission rate settings and that OPV can be reintroduced and withdrawn as needed in moderate transmission rate settings. However, in high transmission rate settings, the conditions that support vaccine-derived outbreaks have only been rare because population immunity has been high. Absent population immunity, the Sabin strains from OPV will be nearly as capable of causing outbreaks as WPV. If post-cessation outbreak responses are followed by new vaccine-derived outbreaks, strategies to restore population
Full Text Available The oral polio vaccine (OPV contains live-attenuated polioviruses that induce immunity by causing low virulence infections in vaccine recipients and their close contacts. Widespread immunization with OPV has reduced the annual global burden of paralytic poliomyelitis by a factor of 10,000 or more and has driven wild poliovirus (WPV to the brink of eradication. However, in instances that have so far been rare, OPV can paralyze vaccine recipients and generate vaccine-derived polio outbreaks. To complete polio eradication, OPV use should eventually cease, but doing so will leave a growing population fully susceptible to infection. If poliovirus is reintroduced after OPV cessation, under what conditions will OPV vaccination be required to interrupt transmission? Can conditions exist in which OPV and WPV reintroduction present similar risks of transmission? To answer these questions, we built a multi-scale mathematical model of infection and transmission calibrated to data from clinical trials and field epidemiology studies. At the within-host level, the model describes the effects of vaccination and waning immunity on shedding and oral susceptibility to infection. At the between-host level, the model emulates the interaction of shedding and oral susceptibility with sanitation and person-to-person contact patterns to determine the transmission rate in communities. Our results show that inactivated polio vaccine (IPV is sufficient to prevent outbreaks in low transmission rate settings and that OPV can be reintroduced and withdrawn as needed in moderate transmission rate settings. However, in high transmission rate settings, the conditions that support vaccine-derived outbreaks have only been rare because population immunity has been high. Absent population immunity, the Sabin strains from OPV will be nearly as capable of causing outbreaks as WPV. If post-cessation outbreak responses are followed by new vaccine-derived outbreaks, strategies to restore
Nakayama, Misako; Shichinohe, Shintaro; Itoh, Yasushi; Ishigaki, Hirohito; Kitano, Mitsutaka; Arikata, Masahiko; Pham, Van Loi; Ishida, Hideaki; Kitagawa, Naoko; Okamatsu, Masatoshi; Sakoda, Yoshihiro; Ichikawa, Takaya; Tsuchiya, Hideaki; Nakamura, Shinichiro; Le, Quynh Mai; Ito, Mutsumi; Kawaoka, Yoshihiro; Kida, Hiroshi; Ogasawara, Kazumasa
H5N1 highly pathogenic avian influenza virus (HPAIV) infection has been reported in poultry and humans with expanding clade designations. Therefore, a vaccine that induces immunity against a broad spectrum of H5N1 viruses is preferable for pandemic preparedness. We established a second H5N1 vaccine candidate, A/duck/Hokkaido/Vac-3/2007 (Vac-3), in our virus library and examined the efficacy of inactivated whole particles of this strain against two clades of H5N1 HPAIV strains that caused severe morbidity in cynomolgus macaques. Virus propagation in vaccinated macaques infected with either of the H5N1 HPAIV strains was prevented compared with that in unvaccinated macaques. This vaccine also prevented propagation of a pandemic (H1N1) 2009 virus in macaques. In the vaccinated macaques, neutralization activity, which was mainly shown by anti-hemagglutinin antibody, against H5N1 HPAIVs in plasma was detected, but that against H1N1 virus was not detected. However, neuraminidase inhibition activity in plasma and T-lymphocyte responses in lymph nodes against H1N1 virus were detected. Therefore, cross-clade and heterosubtypic protective immunity in macaques consisted of humoral and cellular immunity induced by vaccination with Vac-3. PMID:24376571
Full Text Available H5N1 highly pathogenic avian influenza virus (HPAIV infection has been reported in poultry and humans with expanding clade designations. Therefore, a vaccine that induces immunity against a broad spectrum of H5N1 viruses is preferable for pandemic preparedness. We established a second H5N1 vaccine candidate, A/duck/Hokkaido/Vac-3/2007 (Vac-3, in our virus library and examined the efficacy of inactivated whole particles of this strain against two clades of H5N1 HPAIV strains that caused severe morbidity in cynomolgus macaques. Virus propagation in vaccinated macaques infected with either of the H5N1 HPAIV strains was prevented compared with that in unvaccinated macaques. This vaccine also prevented propagation of a pandemic (H1N1 2009 virus in macaques. In the vaccinated macaques, neutralization activity, which was mainly shown by anti-hemagglutinin antibody, against H5N1 HPAIVs in plasma was detected, but that against H1N1 virus was not detected. However, neuraminidase inhibition activity in plasma and T-lymphocyte responses in lymph nodes against H1N1 virus were detected. Therefore, cross-clade and heterosubtypic protective immunity in macaques consisted of humoral and cellular immunity induced by vaccination with Vac-3.
Zaman, Khalequ; Estívariz, Concepción F; Morales, Michelle; Yunus, Mohammad; Snider, Cynthia J; Gary, Howard E; Weldon, William C; Oberste, M Steven; Wassilak, Steven G; Pallansch, Mark A; Anand, Abhijeet
Monovalent type 2 oral poliovirus vaccine (mOPV2) and inactivated poliovirus vaccine (IPV) are used to respond to type 2 poliovirus outbreaks. We aimed to assess the effect of two mOPV2 doses on the type 2 immune response by varying the time interval between mOPV2 doses and IPV co-administration with mOPV2. We did a randomised, controlled, parallel, open-label, non-inferiority, inequality trial at two study clinics in Dhaka, Bangladesh. Healthy infants aged 6 weeks (42-48 days) at enrolment were randomly assigned (1:1:1:1) to receive two mOPV2 doses (each dose consisting of two drops [0·1 mL in total] of about 10 5 50% cell culture infectious dose of type 2 Sabin strain) at intervals of 1 week, 2 weeks, 4 weeks (standard or control group), or 4 weeks with IPV (0·5 mL of type 1 [Mahoney, 40 D-antigen units], type 2 [MEF-1, 8 D-antigen units], and type 3 [Saukett, 32 D-antigen units]) administered intramuscularly with the first mOPV2 dose. We used block randomisation, randomly selecting blocks of sizes four, eight, 12, or 16 stratified by study sites. We concealed randomisation assignment from staff managing participants in opaque, sequentially numbered, sealed envelopes. Parents and clinic staff were unmasked to assignment after the randomisation envelope was opened. Laboratory staff analysing sera were masked to assignment, but investigators analysing data and assessing outcomes were not. The primary outcome was type 2 immune response measured 4 weeks after mOPV2 administration. The primary modified intention-to-treat analysis included participants with testable serum samples before and after vaccination. A non-inferiority margin of 10% and p=0·05 (one-tailed) was used. This trial is registered at ClinicalTrials.gov, number NCT02643368, and is closed to accrual. Between Dec 7, 2015, and Jan 5, 2016, we randomly assigned 760 infants to receive two mOPV2 doses at intervals of 1 week (n=191), 2 weeks (n=191), 4 weeks (n=188), or 4 weeks plus IPV (n=190). Immune
Bellver Capella, Vincente
Vaccines are an extraordinary instrument of immunization of the population against infectious diseases. Around them there are many ethical issues. One of the most debated is what to do with certain groups opposition to vaccination of their children. States have managed in different ways the conflict between the duty of vaccination and the refusal to use vaccines: some impose the vaccination and others simply promote it. In this article we deal with which of these two approaches is the most suitable from an ethical and legal point of view. We stand up for the second option, which is the current one in Spain, and we propose some measures which should be kept in mind to improve immunization programs.
Sun, Mingbo; Ma, Yan; Xu, Yinhua; Yang, Huijuan; Shi, Li; Che, Yanchun; Liao, Guoyang; Jiang, Shude; Zhang, Shumin; Li, Qihan
The World Health Organization has recommended that a Sabin inactivated polio vaccine (IPV) should gradually and synchronously replace oral polio vaccines for routine immunizations because its benefits in eliminating vaccine-associated paralytic poliomyelitis have been reported in different phases of clinical trials. It is also considered important to explore new tetravalent diphtheria, tetanus, and acellular pertussis-Sabin IPV (DTaP-sIPV) candidate vaccines for possible use in developing countries. In this study, the immunogenicity of a combined tetravalent DTaP-sIPV candidate vaccine was investigated in primates by evaluating the neutralizing antibody responses it induced. The dynamic profiles of the antibody responses to each of the separate antigenic components and serotypes of Sabin IPV were determined and their corresponding geometric mean titers were similar to those generated by the tetravalent diphtheria, tetanus, and acellular pertussis-conventional IPV (DTaP-cIPV), the tetravalent diphtheria, tetanus, and acellular pertussis (DTaP), and Sabin IPV vaccines in the control groups. This implies that protective immunogenic effects are conferred by this combined tetravalent formulation. Copyright © 2013 Elsevier Ltd. All rights reserved.
Zerbini, Cristiano A.F.; Ribeiro dos Santos, Rodrigo; Jose Nunes, Maria; Soni, Jyoti; Li, Ping; Jain, Varsha K.; Ofori-Anyinam, Opokua
Abstract The World Health Organization influenza forecast now includes an influenza B strain from each of the influenza B lineages (B/Yamagata and B/Victoria) for inclusion in seasonal influenza vaccines. Traditional trivalent influenza vaccines include an influenza B strain from one lineage, but because two influenza B lineages frequently co-circulate, the effectiveness of trivalent vaccines may be reduced in seasons of influenza B vaccine-mismatch. Thus, quadrivalent vaccines may potentiall...
Stimulation of mucosal immune response following oral administration of enterotoxigenic Escherichia coli fimbriae (CFA/I) entrapped in liposomes in conjunction with inactivated whole-cell Vibrio cholerae vaccine.
Dima, V F; Ionescu, M D; Palade, R; Balotescu, C; Becheanu, G; Dima, S V
In this study, we have searched for an effective mucosal vaccine. An oral enterotoxigenic E. coli vaccine containing colonization factor antigen (CFA/I) associated with inactivated whole-cell V. cholerae vaccine (WCV) has been tested for safety and immunogenicity in animals. Five groups of animals were used. The results showed the following: (a) vaccine containing CFA/I antigen entrapped in liposomes and associated with WCV (batch C) had increased titers of specific antibodies to CFA/I antigen in 15 to 18 (83.3%) animals; (b) specific Peyer's patches (PP), lymph nodes (LN) and spleen (SPL) lymphocytes proliferation was detected following in vitro restimulation with CFA/I antigen or WCV. This response gradually increased to the highest value by the 35th postimmunization day. Moreover, lower PP, LN and spleen (SPL) proliferation was observed in rabbits receiving soluble CFA/I antigen (S-CFA/I) or free liposomes (F-L) alone; (c) adhesion of E. coli H10407 strain labelled with 3H-leucine in immunized and control animals revealed the following local effects: (i) protection of rabbit intestinal mucosa against virulent E. coli cells; (ii) inhibition of adhesion of ETEC bacteria to intestinal mucosa and (iii) significantly faster release of E. coli H 10407 strain labelled with 3H-leucine from the intestinal tract of immunized animals. The histopathological and electron microscope findings confirmed the above results. The experimental results point out an efficient protection against infection with E. coli strains (ETEC), after mucosal vaccination with CFA/I antigen entrapped in liposomes associated with inactivated whole-cell Vibrio cholerae as immunological adjuvant.
Sanders, Barbara P; Liu, Ying; Brandjes, Alies; van Hoek, Vladimir; de Los Rios Oakes, Isabel; Lewis, John; Wimmer, Eckard; Custers, Jerome H H V; Schuitemaker, Hanneke; Cello, Jeronimo; Edo-Matas, Diana
Brunenders, a type I poliovirus (PV) strain, was developed in 1952 by J. F. Enders and colleagues through serial in vitro passaging of the parental Brunhilde strain, and was reported to display partial neuroattenuation in monkeys. This phenotype of attenuation encouraged two vaccine manufacturers to adopt Brunenders as the type I component for their inactivated poliovirus vaccines (IPVs) in the 1950s, although today no licensed IPV vaccine contains Brunenders. Here we confirmed, in a transgenic mouse model, the report of Enders on the reduced neurovirulence of Brunenders. Although dramatically neuroattenuated relative to WT PV strains, Brunenders remains more virulent than the attenuated oral vaccine strain, Sabin 1. Importantly, the neuroattenuation of Brunenders does not affect in vitro growth kinetics and in vitro antigenicity, which were similar to those of Mahoney, the conventional type I IPV vaccine strain. We showed, by full nucleotide sequencing, that Brunhilde and Brunenders differ at 31 nucleotides, eight of which lead to amino acid changes, all located in the capsid. Upon exchanging the Brunenders capsid sequence with that of the Mahoney capsid, WT neurovirulence was regained in vivo, suggesting a role for the capsid mutations in Brunenders attenuation. To date, as polio eradication draws closer, the switch to using attenuated strains for IPV is actively being pursued. Brunenders preceded this novel strategy as a partially attenuated IPV strain, accompanied by decades of successful use in the field. Providing data on the attenuation of Brunenders may be of value in the further construction of attenuated PV strains to support the grand pursuit of the global eradication of poliomyelitis.
Menning, Lisa; Garg, Gaurav; Pokharel, Deepa; Thrush, Elizabeth; Farrell, Margaret; Kodio, Frederic Kunjbe; Veira, Chantal Laroche; Wanyoike, Sarah; Malik, Suleman; Patel, Manish; Rosenbauer, Oliver
The requirements under objective 2 of the Polio Eradication and Endgame Strategic Plan 2013-2018-to introduce at least 1 dose of inactivated poliomyelitis vaccine (IPV); withdraw oral poliomyelitis vaccine (OPV), starting with the type 2 component; and strengthen routine immunization programs-set an ambitious series of targets for countries. Effective implementation of IPV introduction and the switch from trivalent OPV (containing types 1, 2, and 3 poliovirus) to bivalent OPV (containing types 1 and 3 poliovirus) called for intense global communications and coordination on an unprecedented scale from 2014 to 2016, involving global public health technical agencies and donors, vaccine manufacturers, World Health Organization and United Nations Children's Fund regional offices, and national governments. At the outset, the new program requirements were perceived as challenging to communicate, difficult to understand, unrealistic in terms of timelines, and potentially infeasible for logistical implementation. In this context, a number of core areas of work for communications were established: (1) generating awareness and political commitment via global communications and advocacy; (2) informing national decision-making, planning, and implementation; and (3) in-country program communications and capacity building, to ensure acceptance of IPV and continued uptake of OPV. Central to the communications function in driving progress for objective 2 was its ability to generate a meaningful policy dialogue about polio vaccines and routine immunization at multiple levels. This included efforts to facilitate stakeholder engagement and ownership, strengthen coordination at all levels, and ensure an iterative process of feedback and learning. This article provides an overview of the global efforts and challenges in successfully implementing the communications activities to support objective 2. Lessons from the achievements by countries and partners will likely be drawn upon when
Bragazzi, Nicola Luigi; Gianfredi, Vincenza; Villarini, Milena; Rosselli, Roberto; Nasr, Ahmed; Hussein, Amr; Martini, Mariano; Behzadifar, Masoud
Vaccines are public health interventions aimed at preventing infections-related mortality, morbidity, and disability. While vaccines have been successfully designed for those infectious diseases preventable by preexisting neutralizing specific antibodies, for other communicable diseases, additional immunological mechanisms should be elicited to achieve a full protection. "New vaccines" are particularly urgent in the nowadays society, in which economic growth, globalization, and immigration are leading to the emergence/reemergence of old and new infectious agents at the animal-human interface. Conventional vaccinology (the so-called "vaccinology 1.0") was officially born in 1796 thanks to the contribution of Edward Jenner. Entering the twenty-first century, vaccinology has shifted from a classical discipline in which serendipity and the Pasteurian principle of the three I s (isolate, inactivate, and inject) played a major role to a science, characterized by a rational design and plan ("vaccinology 3.0"). This shift has been possible thanks to Big Data, characterized by different dimensions, such as high volume, velocity, and variety of data. Big Data sources include new cutting-edge, high-throughput technologies, electronic registries, social media, and social networks, among others. The current mini-review aims at exploring the potential roles as well as pitfalls and challenges of Big Data in shaping the future vaccinology, moving toward a tailored and personalized vaccine design and administration.
Immunogenicity and safety of an inactivated hepatitis A vaccine when coadministered with Diphtheria-tetanus-acellular pertussis and haemophilus influenzae type B vaccines in children 15 months of age.
Trofa, Andrew F; Klein, Nicola P; Paul, Ian M; Michaels, Marian G; Goessler, Mary; Chandrasekaran, Vijayalakshmi; Blatter, Mark
This study (NCT00197236) evaluated the safety and immunogenicity of a hepatitis A virus (HAV) vaccine when coadministered with diphtheria-tetanus-acellular pertussis (DTaP) and Haemophilus influenzae type b (Hib) vaccines in children 15 months of age. This was an open-labeled, multicenter study with healthy subjects enrolled and randomized (1:1:1) into 3 treatment groups. A total of 394 subjects received the first study vaccinations at 15 months of age. Group HAV (N = 135) received 2 doses of HAV vaccine 6 to 9 months apart. Group HAV+DTaP+Hib (N = 127) received HAV vaccine coadministered with DTaP and Hib vaccines and the second dose of HAV vaccine, 6 to 9 months later. Group DTaP+Hib→HAV (N = 132) received the DTaP and Hib vaccines at 15 months of age, followed by HAV vaccine 30 days later and the second dose of HAV vaccine 7 to 10 months after the DTaP+Hib vaccines. Immune responses were evaluated before the first study vaccination and 30 days after each vaccine dose. Solicited, unsolicited, and serious adverse events were collected. After 2 doses of the HAV vaccine, all subjects in the 3 groups were seropositive. The geometric mean concentration of anti-HAV antibodies ranged between 1625.1 and 1904.4 mIU/mL. Coadministration of the 3 vaccines did not impact immunogenicity of the HAV, DTaP, or Hib vaccines. Vaccines were well tolerated in all groups. A 2-dose schedule of HAV vaccine was well tolerated and immunogenic when administered to children starting at 15 months of age. Immune responses to the DTaP or Hib vaccines were similar whether they were administered alone or were coadministered with the HAV vaccine.
Tay, Chee Geap; Ong, Lai Choo; Goh, Khean Jin; Rahmat, Kartini; Fong, Choong Yi
We report a previously well 10-month-old Somalian girl who acquired asymmetric lower limb weakness in July 2013 in Mogadishu, Banadir, before arriving in Malaysia at 12 months of age. In May 2013, there was a wild poliomyelitis outbreak in that area, as reported by the World Health Organization. Laboratory investigation, including cerebrospinal fluid, was unremarkable, and electrophysiological studies showed active axonal denervation in the left lower limb. The whole spine T2-weighted MRI revealed non-enhancing hyperintensities of the bilateral anterior horn cells, predominantly on the left side at T11-12. The viral isolations from two stool specimens at her presentation to our centre, 2 months after the onset of illness and 2 weeks apart, were negative. Despite lacking the acute virological evidence of poliomyelitis, in view of the girl's clinical, electrophysiological and classical spinal neuroradiological features, together with her temporal relationship with a World Health Organization reported wild poliomyelitis outbreak, we believe these findings are consistent with a diagnosis of imported poliomyelitis. A review at 30 months of age showed persistent left lower limb monoplegia with little recovery. Our patient reiterates the importance of maintaining awareness of wild polio importation, and keeping abreast of the latest news of global poliomyelitis outbreaks when treating patients with flaccid paralysis, even if they arrive from non-endemic poliomyelitis areas. Copyright © 2015 Elsevier Ltd. All rights reserved.
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.
Ma, F; Yang, J; Kang, G; Sun, Q; Lu, P; Zhao, Y; Wang, Z; Luo, J; Wang, Z
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 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. Copyright © 2016. Published by Elsevier Ltd.
Nielsen, Nete Munk; Rostgaard, Klaus; Juel, Knud
BACKGROUND: Few studies have described mortality and cause of death among persons with a history of polio. METHODS: We identified a group of patients diagnosed with poliomyelitis in Copenhagen between 1919 and 1954. We obtained information on vital status through May 1997 and on cause of death...... by linkage with the Danish Civil Registration System and the Danish Cause-of-Death Register. Overall and cause-specific standardized mortality ratios served as the measure of mortality risk relative to that of the general population. RESULTS: We observed 1295 deaths among 5977 polio patients compared...... with an expected 1141 deaths (standardized mortality ratio = 1.14; 95% confidence interval = 1.07-1.20). Excess mortality was restricted to polio patients with a history of severe paralysis of the extremities (1.69; 1.32-2.15) or patients who had been treated for respiratory failure during the epidemics (2.71; 2...
Romanenkova, N I; Bichurina, M A; Rozaeva, N R; Pogrebnaia, T N
Analysis of results of virological study of material from children of migrants and evaluation of intensity of immunity against polioviruses in these children. 1668 feces samples from patients with acute flaccid paralysis and contact individuals and 479 feces samples from healthy children from families of migrants, as well as 1012 blood sera of children aged 3 - 4 and 14 - 15 years living in the same territory of Russia, and 169 blood sera of children of migrants were studied. Polioviruses and non-polio enteroviruses were isolated by standard procedures recommended by WHO in 3 cell cultures - RD, L20B and Hep-2. Virus identification was carried out by microneutralization test with rabbit antisera against poliomyelitisvirus, RIVM (Bilthoven, Netherlands). For intra-type differentiation EIA and PCRwere used. Antibody titers were determined in microneutralization reaction with reference poliovirus vaccines strains in Hep-2 cell culture. The frequency of detection of polioviruses in children of migrants was significantly higher than in patients with acute flaccid paralysis. In a larger percent of cases children of migrants did not have protective antibody titers against polioviruses of all the 3 serotypes. Migrants as a significant source of poliovirus detection may be an indicator group for detection of signs of unfavorable epidemic situation. Based on the results of epidemiologic surveillance of migrants the fact of import of wild poliovirus into North-West of Russia with the absence of poliomyelitis was proven, which confirms an important role of this form of monitoring in the system of poliomyelitis control.
Monitoring of implementation of international programs of poliomyelitis eradication, and measles and rubella elimination in the Republic of Belarus based on results of molecular-epidemiologic studies of 2009 - 2010. 271 viral agents isolated from children with acute flaccid paralysis syndrome, other diseases, healthy children and from sewage water within the framework of poliomyelitis control implementation were identified by serological and molecular methods. Blood sera of 528 patients with fever and rash were examined for the presence of IgM to measles and rubella virus, 418 - for the presence of IgM to parvovirus B19 and parvovirus DNA. Blood sera of 33 pregnant women and 64 children with signs of intrauterine infection were studied for IgM and IgG antibodies to rubella virus. Measles virus was isolated, N-gene sequence and phylogenetic analysis carried out. The studies performed confirmed that indigenous wild polioviruses in the country do not circulate, imported wild or vaccine-related polioviruses were also not detected. Measles and rubella morbidity in the Republic of Belarus was less than 1 in 1 000 000. 2 cases of rubella (2009) and 1 case of measles (2010) was detected during adequate control level: the rate of detection of patients with fever and rash, in whom measles and rubella diagnosis was excluded by the results of laboratory examination, was more than 2 in 100 000 of the population. The etiologic agent in more than 20% of diseases with fever and rash was parvovirus B19. A single case of measles was caused by genotype D8 virus imported from India. The data obtained give evidence to conformance of the poliomyelitis, measles, rubella, innate rubella syndrome control implemented in the Republic of Belarus to WHO recommendations; maintenance of status of country as free from poliomyelitis and achievement of main criteria of elimination of both measles and rubella by 2010.
Werthel, Jean-David; Schoch, Bradley; Sperling, John W; Cofield, Robert; Elhassan, Bassem T
Polio infection can often lead to orthopedic complications such as arthritis, osteoporosis, muscle weakness, skeletal deformation, and chronic instability of the joints. The purpose of this study was to assess the outcomes and associated complications of arthroplasty in shoulders with sequelae of poliomyelitis. Seven patients (average age, 70 years) were treated between 1976 and 2013 with shoulder arthroplasty for the sequelae of polio. One patient underwent reverse shoulder arthroplasty, 2 had a hemiarthroplasty, and 4 had total shoulder arthroplasty. Average follow-up was 87 months. Outcome measures included pain, range of motion, and postoperative modified Neer ratings. Overall pain scores improved from 5 to 1.6 points (on a 5-point scale) after shoulder arthroplasty. Six shoulders had no or mild pain at latest follow-up, and 6 shoulders rated the result as much better or better. Mean shoulder elevation improved from 72° to 129°, and external rotation improved from 11° to 56°. Average strength in elevation decreased from 3.9 to 3.4 postoperatively, and external rotation strength decreased from 3.9 to 3.3. This, however, did not reach significance. Evidence of muscle imbalance with radiographic instability was found in 4 shoulders that demonstrated superior subluxation, anterior subluxation, or both. This remained asymptomatic. No shoulder required revision or reoperation. Shoulder arthroplasty provides significant pain relief and improved motion in patients with sequelae of poliomyelitis. Muscle weakness may be responsible for postoperative instability, and careful selection of the patient with good upper extremity muscles must be made. Copyright © 2016 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.
Diop, Ousmane M; Burns, Cara C; Sutter, Roland W; Wassilak, Steven G; Kew, Olen M
Since the World Health Assembly's 1988 resolution to eradicate poliomyelitis, one of the main tools of the World Health Organization (WHO) Global Polio Eradication Initiative (GPEI) has been the live, attenuated oral poliovirus vaccine (OPV). OPV might require several doses to induce immunity but provides long-term protection against paralytic disease. Through effective use of OPV, GPEI has brought polio to the threshold of eradication. Wild poliovirus type 2 (WPV2) was eliminated in 1999, WPV3 has not been detected since November 2012, and WPV1 circulation appears to be restricted to parts of Pakistan and Afghanistan. However, continued use of OPV carries two key risks. The first, vaccine-associated paralytic poliomyelitis (VAPP) has been recognized since the early 1960s. VAPP is a very rare event that occurs sporadically when an administered dose of OPV reverts to neurovirulence and causes paralysis in the vaccine recipient or a nonimmune contact. VAPP can occur among immunologically normal vaccine recipients and their contacts as well as among persons who have primary immunodeficiencies (PIDs) manifested by defects in antibody production; it is not associated with outbreaks. The second, the emergence of genetically divergent, neurovirulent vaccine-derived polioviruses (VDPVs) was recognized more recently. Circulating VDPVs (cVDPVs) resemble WPVs and, in areas with low OPV coverage, can cause polio outbreaks. Immunodeficiency-associated VDPVs (iVDPVs) can replicate and be excreted for years in some persons with PIDs; GPEI maintains a registry of iVDPV cases. Ambiguous VDPVs (aVDPVs) are isolates that cannot be classified definitively. This report updates previous surveillance summaries and describes VDPVs detected worldwide during January 2014-March 2015. Those include new cVDPV outbreaks in Madagascar and South Sudan, and sharply reduced type 2 cVDPV (cVDPV2) circulation in Nigeria and Pakistan during the latter half of 2014. Eight newly identified persons in
Wang, Long; Chandrasekaran, Vijayalakshmi; Domachowske, Joseph B; Li, Ping; Innis, Bruce L; Jain, Varsha K
Viruses from 2 influenza B lineages co-circulate, leading to suboptimal protection with trivalent influenza vaccines (TIV). Quadrivalent influenza vaccines (QIV) containing both lineages offer broader protection. We compared inactivated seasonal QIV versus TIV (15 and 7.5 μg hemagglutinin [HA] for each influenza strain, respectively) in a phase II randomized (1 : 1), observer-blind trial in US children 6-35 months of age (identifier NCT01974895). The primary objective was to evaluate immune responses induced by QIV for the 4 vaccine strains 28 days after completion of vaccination. A secondary objective was to demonstrate superiority of QIV versus TIV for the B/Victoria strain contained in QIV but not TIV. Immunogenicity was evaluated in the per-protocol cohort (N = 280), and safety was evaluated in the intent-to-treat cohort (N = 314). Seroconversion rates (SCRs) for QIV were 80.4% (95% confidence interval [CI], 73.0%-86.6%), 72.0% (95% CI, 63.9%-79.2%), 86.0% (95% CI, 79.2%-91.2%), and 66.4% (95% CI, 58.1%-74.1%) for A/H1N1, A/H3N2, B/Yamagata, and B/Victoria, respectively. Quadrivalent influenza vaccines demonstrated immunogenic superiority over TIV for B/Victoria with a geometric mean titer ratio of 4.73 (95% CI, 3.73%-5.99%) and SCR difference of 54.02% (95% CI, 43.88%-62.87%). Safety was similar between the vaccine groups despite the QIV's higher antigen content. No serious adverse events were reported related to vaccination. Quadrivalent influenza vaccine (15 µg HA/strain) was immunogenic with an acceptable safety profile. The next phase of its development in children 6-35 months of age is a phase III trial in countries where it is not yet licensed. In countries where it is already licensed, a switch from TIV to QIV would provide broader protection in this vulnerable group. © The Author 2015. Published by Oxford University Press on behalf of the Pediatric Infectious Diseases Society.
Wang, Long; Chandrasekaran, Vijayalakshmi; Domachowske, Joseph B.; Li, Ping; Innis, Bruce L.; Jain, Varsha K.
Background Viruses from 2 influenza B lineages co-circulate, leading to suboptimal protection with trivalent influenza vaccines (TIV). Quadrivalent influenza vaccines (QIV) containing both lineages offer broader protection. Methods We compared inactivated seasonal QIV versus TIV (15 and 7.5 μg hemagglutinin [HA] for each influenza strain, respectively) in a phase II randomized (1 : 1), observer-blind trial in US children 6–35 months of age (identifier NCT01974895). The primary objective was to evaluate immune responses induced by QIV for the 4 vaccine strains 28 days after completion of vaccination. A secondary objective was to demonstrate superiority of QIV versus TIV for the B/Victoria strain contained in QIV but not TIV. Immunogenicity was evaluated in the per-protocol cohort (N = 280), and safety was evaluated in the intent-to-treat cohort (N = 314). Results Seroconversion rates (SCRs) for QIV were 80.4% (95% confidence interval [CI], 73.0%–86.6%), 72.0% (95% CI, 63.9%–79.2%), 86.0% (95% CI, 79.2%–91.2%), and 66.4% (95% CI, 58.1%–74.1%) for A/H1N1, A/H3N2, B/Yamagata, and B/Victoria, respectively. Quadrivalent influenza vaccines demonstrated immunogenic superiority over TIV for B/Victoria with a geometric mean titer ratio of 4.73 (95% CI, 3.73%–5.99%) and SCR difference of 54.02% (95% CI, 43.88%–62.87%). Safety was similar between the vaccine groups despite the QIV's higher antigen content. No serious adverse events were reported related to vaccination. Conclusions Quadrivalent influenza vaccine (15 µg HA/strain) was immunogenic with an acceptable safety profile. The next phase of its development in children 6–35 months of age is a phase III trial in countries where it is not yet licensed. In countries where it is already licensed, a switch from TIV to QIV would provide broader protection in this vulnerable group. PMID:26407273
Immunogenicity and safety of primary and booster vaccination with 2 investigational formulations of diphtheria, tetanus and Haemophilus influenzae type b antigens in a hexavalent DTPa-HBV-IPV/Hib combination vaccine in comparison with the licensed Infanrix hexa
Vesikari, Timo; Rivera, Luis; Korhonen, Tiina; Ahonen, Anitta; Cheuvart, Brigitte; Hezareh, Marjan; Janssens, Winnie; Mesaros, Narcisa
ABSTRACT Safety and immunogenicity of 2 investigational formulations of diphtheria, tetanus and Haemophilus influenzae type b antigens of the combined diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliomyelitis-Hib vaccine (DTPa-HBV-IPV/Hib) were evaluated in a Primary (NCT01248884) and a Booster vaccination (NCT01453998) study. In the Primary study, 721 healthy infants (randomized 1:1:1) received 3 doses of DTPa-HBV-IPV/Hib formulation A (DATAPa-HBV-IPV/Hib), or B (DBTBPa-HBV-IPV/Hib) or the licensed DTPa-HBV-IPV/Hib vaccine (Infanrix hexa, GSK; control group) at 2, 3, 4 months of age. Infants were planned to receive a booster dose at 12–15 months of age with the same formulation received in the Primary study; however, following high incidence of fever associated with the investigational formulations in the Primary study, the Booster study protocol was amended and all infants yet to receive a booster dose (N = 385) received the licensed vaccine. In the Primary study, non-inferiority of 3-dose vaccination with investigational formulations compared with the licensed vaccine was not demonstrated due to anti-pertactin failing to meet the non-inferiority criterion. Post-primary vaccination, most infants had seroprotective levels of anti-diphtheria (100% of infants), anti-tetanus antigens (100%), against hepatitis B (≥ 97.5% across groups), polyribosyl-ribitol-phosphate (≥ 88.0%) and poliovirus types 1–3 (≥ 90.5%). Seropositivity rates for each pertussis antigen were 100% in all groups. Higher incidence of fever (> 38°C) was reported in infants receiving the investigational formulations (Primary study: 75.0% [A] and 72.1% [B] vs 58.8% [control]; Booster study, before amendment: 49.4% and 46.6% vs 37.4%, respectively). The development of the investigational formulations was not further pursued. PMID:28340322
Shen, Ling; Chen, Crystal Y; Huang, Dan; Wang, Richard; Zhang, Meihong; Qian, Lixia; Zhu, Yanfen; Zhang, Alvin Zhuoran; Yang, Enzhuo; Qaqish, Arwa; Chumakov, Konstantin; Kouiavskaia, Diana; Vignuzzi, Marco; Nathanson, Neal; Macadam, Andrew J; Andino, Raul; Kew, Olen; Xu, Junfa; Chen, Zheng W
Despite a great deal of prior research, the early pathogenic events in natural oral poliovirus infection remain poorly defined. To establish a model for study, we infected 39 macaques by feeding them single high doses of the virulent Mahoney strain of wild type 1 poliovirus. Doses ranging from 10 7 to 10 9 50% tissue culture infective doses (TCID 50 ) consistently infected all the animals, and many monkeys receiving 10 8 or 10 9 TCID 50 developed paralysis. There was no apparent difference in the susceptibilities of the three macaque species (rhesus, cynomolgus, and bonnet) used. Virus excretion in stool and nasopharynges was consistently observed, with occasional viremia, and virus was isolated from tonsils, gut mucosa, and draining lymph nodes. Viral replication proteins were detected in both epithelial and lymphoid cell populations expressing CD155 in the tonsil and intestine, as well as in spinal cord neurons. Necrosis was observed in these three cell types, and viral replication in the tonsil/gut was associated with histopathologic destruction and inflammation. The sustained response of neutralizing antibody correlated temporally with resolution of viremia and termination of virus shedding in oropharynges and feces. For the first time, this model demonstrates that early in the infectious process, poliovirus replication occurs in both epithelial cells (explaining virus shedding in the gastrointestinal tract) and lymphoid/monocytic cells in tonsils and Peyer's patches (explaining viremia), extending previous studies of poliovirus pathogenesis in humans. Because the model recapitulates human poliovirus infection and poliomyelitis, it can be used to study polio pathogenesis and to assess the efficacy of candidate antiviral drugs and new vaccines. IMPORTANCE Early pathogenic events of poliovirus infection remain largely undefined, and there is a lack of animal models mimicking natural oral human infection leading to paralytic poliomyelitis. All 39 macaques fed with
Full Text Available Abstract Background Nowadays there is a debate about the indication of the oral whole-cell/recombinant B-subunit cholera vaccine (WC/rBS in traveller's diarrhoea. However, a cost-benefit analysis based on real data has not been published. Methods A cost-effectiveness and cost-benefit study of the oral cholera vaccine (WC/rBS, Dukoral® for the prevention of traveller's diarrhoea (TD was performed in subjects travelling to cholera risk areas. The effectiveness of WC/rBS vaccine in the prevention of TD was analyzed in 362 travellers attending two International Vaccination Centres in Spain between May and September 2005. Results The overall vaccine efficacy against TD was 42,6%. Direct healthcare-related costs as well as indirect costs (lost vacation days subsequent to the disease were considered. Preventive vaccination against TD resulted in a mean saving of 79.26 € per traveller. Conclusion According to the cost-benefit analysis performed, the recommendation for WC/rBS vaccination in subjects travelling to zones at risk of TD is beneficial for the traveller, regardless of trip duration and visited continent.
Yamanaka, Takashi; Bannai, Hiroshi; Nemoto, Manabu; Tsujimura, Koji; Kondo, Takashi; Matsumura, Tomio
In 2010, the World Organisation for Animal Health recommended the inclusion of a Florida sublineage clade2 strain of equine influenza virus (H3N8), which is represented by A/equine/Richmond/1/07 (Richmond07), in equine influenza vaccines. Here, we evaluate the antigenic differences between Japanese vaccine strains and Richmond07 by performing hemagglutination inhibition (HI) assays. Ferret antiserum raised to A/equine/La Plata/93 (La Plata93), which is a Japanese vaccine strain, reacted with Richmond07 at a similar titer to La Plata93. Moreover, two hundred racehorses exhibited similar geometric mean HI antibody titers against La Plata93 and Richmond07 (73.1 and 80.8, respectively). Therefore, we can expect the antibody induced by the current Japanese vaccines to provide some protection against Richmond07-like viruses.
Whiteside, Theresa L.; Piazza, Paolo; Reiter, Amanda; Stanson, Joanna; Connolly, Nancy C.; Rinaldo, Charles R.; Riddler, Sharon A.
In preparation for a pilot clinical trial in patients with chronic human immunodeficiency virus type 1 (HIV-1) infection, a novel dendritic cell (DC)-based vaccine is being manufactured. The trial will test the hypothesis that isolated endogenous virus presented by DCs serves as a potent immunogen for activation of CD8+ and CD4+ T cells specific for a broad range of autologous HIV-1 antigens. Production of the vaccine under good manufacture practice conditions involves (i) autologous virus is...
Recuenco, Sergio; Warnock, Eli; Osinubi, Modupe O V; Rupprecht, Charles E
In the USA, rabies vaccines (RVs) are licensed for intramuscular (IM) use only, although RVs are licensed for use by the intradermal (ID) route in many other countries. Recent limitations in supplies of RV in the USA reopened discussions on the more efficient use of available biologics, including utilization of more stringent risk assessments, and potential ID RV administration. A clinical trial was designed to compare the immunogenic and adverse effects of a purified chicken embryo cell (PCEC) RV administered ID or IM. Enrollment was designed in four arms, ID Pre-Exposure Prophylaxis (Pre-EP), IM Pre-EP, ID Booster, and IM Booster vaccination. Enrollment included 130 adult volunteers. The arms with IM administration received vaccine according to the current ACIP recommendations: Pre-EP, three 1mL (2.5 I.U.) RV doses, each on day 0, 7, and 21; or a routine Booster, one 1ml dose. The ID groups received the same schedule, but doses administered were in a volume of 0.1mL (0.25 I.U.). The rate of increase in rabies virus neutralizing antibody titers 14-21days after vaccination were similar in the ID and correspondent IM groups. The GMT values for ID vaccination were slightly lower than those for IM vaccination, for both naïve and booster groups, and these differences were statistically significant by t-test. Fourteen days after completing vaccination, all individuals developed RV neutralizing antibody titers over the minimum arbitrary value obtained with the rapid fluorescent focus inhibition test (RFFIT). Antibodies were over the set threshold until the end of the trial, 160days after completed vaccination. No serious adverse reactions were reported. Most frequent adverse reactions were erythema, induration and tenderness, localized at the site of injection. Multi use of 1mL rabies vaccine vials for ID doses of 0.1 was demonstrated to be both safe and inmunogenic. Copyright © 2017 Elsevier Ltd. All rights reserved.
Full Text Available An association between an adjuvanted (AS03 A/H1N1 pandemic vaccine and narcolepsy has been reported in Europe.To assess narcolepsy risk following administration of a similar vaccine in Quebec.Retrospective population-based study.Neurologists and lung specialists in the province were invited to report narcolepsy cases to a single reference centre.Patients were interviewed by two sleep experts and standard diagnostic tests were performed. Immunization status was verified in the provincial pandemic influenza vaccination registry.Confirmed narcolepsy with or without cataplexy with onset of excessive daytime sleepiness between January 1st, 2009, and December 31st, 2010. Relative risks (RRs were calculated using a Poisson model in a cohort analysis, by a self-controlled case series (SCCS and a case-control method.A total of 24 cases were included and overall incidence rate was 1.5 per million person-years. A cluster of 7 cases was observed among vaccinated persons in the winter 2009-2010. In the primary cohort analysis, 16-week post-vaccination RR was 4.32 (95% CI: 1.50-11.12. RR was 2.07 (0.70-6.17 in the SCCS, and 1.48 (0.37-7.03 using the case-control method. Estimates were lower when observation was restricted to the period of pandemic influenza circulation, and tended to be higher in persons <20 years old and for cataplexy cases.Results are compatible with an excess risk of approximately one case per million vaccine doses, mainly in persons less than 20 years of age. However, a confounding effect of the influenza infection cannot be ruled out.
Halstead, L.S.; Wiechers, D.O.
This book contains 32 selections. Some of the titles are: Late effects of Polio: Historical Perspectives; Sleep-Disordered Breathing as a Late Effect of Poliomyelitis; Clinical Subtypes, DNA Repair Efficiency, and Therapeutic Trials in the Post-Polio Syndromes; and Post-Polio Muscle Function.
The Clinico-epidemological characteristics of two confirmed cases of poliomyelitis detected by Acute Flaccid Paralysis (AFP) surveillance in Osun State of Nigeria after almost 6 years of the last confirmed case in the State was reported to provide information for formulating possible aetiological hypothesis and to adequately ...
Drabo, Koiné Maxime; Nana, Félicité; Kouassi, Kouassi Lazare; Konfé, Salifou; Hien, Hervé; Saizonou, Jacques; Ouedraogo, Tinoaga Laurent
The global initiative for poliomyelitis eradication can only remain relevant if survey systems are regularly assessed. In order to identify shortcomings and to propose improvement, the data collection and transmission during case investigation were assessed in the Banfora health district in Burkina Faso. The survey targeted six (6) primary health centres, the district laboratory and the national laboratory, all involved in the poliomyelitis surveillance system. Data from registers, forms documenting suspected cases, stool sample forms and weekly reports were collected by means of a data grid. Data from actors involved in the poliomyelitis case investigation system were collected by means of an individual questionnaire. The reactivity of investigating suspected cases was satisfactory with a median alert questionnaire notification time of 18 hours. The completeness of the reporting system was satisfactory. Nevertheless, the promptness of data management by primary heath centres and the national laboratory remained unsatisfactory. Evaluation of data management revealed logistic and organization shortcomings. The overall efficacy of the poliomyelitis surveillance could be improved by using management tools for laboratory supplies, collecting data related to the homes of suspected cases and implementing a cold chain maintenance plan.
ten Harkel, A. D.; van Lieshout, J. J.; Wieling, W.
A 59-year old woman who presented with postural dizziness 50 years after an acute episode of poliomyelitis is described. There were no new neurological signs and no evidence of motor neuron disease. She had postural hypotension with an abnormal Valsalva. Investigations led to a diagnosis of
-haired to severe poliomyelitis with respiratory paralysis. .... brisk knee and ankle jerks, and (4) apprehensIOn and restlessness. ... relatively short time (3-7 days usually). .... waves. V2-V4. Q-T interval 0·3 seconds. -upper limit of normal. Pulse.
Development and preclinical evaluation of safety and immunogenicity of an oral ETEC vaccine containing inactivated E. coli bacteria overexpressing colonization factors CFA/I, CS3, CS5 and CS6 combined with a hybrid LT/CT B subunit antigen, administered alone and together with dmLT adjuvant.
Holmgren, J; Bourgeois, L; Carlin, N; Clements, J; Gustafsson, B; Lundgren, A; Nygren, E; Tobias, J; Walker, R; Svennerholm, A-M
A first-generation oral inactivated whole-cell enterotoxigenic Escherichia coli (ETEC) vaccine, comprising formalin-killed ETEC bacteria expressing different colonization factor (CF) antigens combined with cholera toxin B subunit (CTB), when tested in phase III studies did not significantly reduce overall (generally mild) ETEC diarrhea in travelers or children although it reduced more severe ETEC diarrhea in travelers by almost 80%. We have now developed a novel more immunogenic ETEC vaccine based on recombinant non-toxigenic E. coli strains engineered to express increased amounts of CF antigens, including CS6 as well as an ETEC-based B subunit protein (LCTBA), and the optional combination with a nontoxic double-mutant heat-labile toxin (LT) molecule (dmLT) as an adjuvant. Two test vaccines were prepared under GMP: (1) A prototype E. coli CFA/I-only formalin-killed whole-cell+LCTBA vaccine, and (2) A "complete" inactivated multivalent ETEC-CF (CFA/I, CS3, CS5 and CS6 antigens) whole-cell+LCTBA vaccine. These vaccines, when given intragastrically alone or together with dmLT in mice, were well tolerated and induced strong intestinal-mucosal IgA antibody responses as well as serum IgG and IgA responses to each of the vaccine CF antigens as well as to LT B subunit (LTB). Both mucosal and serum responses were further enhanced (adjuvanted) when the vaccines were co-administered with dmLT. We conclude that the new multivalent oral ETEC vaccine, both alone and especially in combination with the dmLT adjuvant, shows great promise for further testing in humans. Copyright © 2013 Elsevier Ltd. All rights reserved.
Control of Salmonella enterica serovar Enteritidis in laying hens by inactivated Salmonella Enteritidis vaccines "Controle de Salmonella enterica sorovar Enteritidis em poedeiras comerciais com a utilização de vacinas inativadas"
Oliveiro Caetano de Freitas Neto
Full Text Available Salmonella Enteritidis is one of the agents that is responsible for outbreaks of human foodborne salmonellosis caused by Salmonella Enteritidis and is generally associated with the consumption of poultry products. Inactivated Salmonella Enteritidis cell vaccine is one of the available methods to control Salmonella Enteritidis in breeders and laying hens, however results in terms of efficacy vary. This vaccine has never been tested in Brazil, therefore, the present work was carried out to assess three commercial inactivated Salmonella Enteritidis vaccines allowed in Brazil. Four hundred white light variety commercial laying hens were obtained at one-day-of age. At eight weeks old, the birds were divided into four groups with one hundred animals each. Birds from three groups (V1, V2 and V3 received different intramuscular vaccines, followed by a booster dose at 16 weeks of age. Birds from another group (CG were not vaccinated. When the laying hens were 20, 25 and 31 weeks old, 13 from each group were transferred to another room and were challenged by inoculating 2 mL neat culture of Salmonella Enteritidis. On the second day after each challenge, the caecal contents, spleen, liver and ovary of three birds from each group were analyzed for the presence of Salmonella Enteritidis. Twice a week a cloacal swab of each bird was taken and all eggs laid were examined for the presence of Salmonella Enteritidis. After four consecutive negative cloacal swabs in all the groups, the birds were sacrificed so as to examine the liver, caecal contents and ovaries. Overall, the inactivated vaccine used in group V3 reduced Salmonella Enteritidis in the feces and eggs. A very small amount of Salmonella was found in the spleen, liver, ovary and caeca of the birds in the four groups during the whole experiment. In general, inactivated Salmonella Enteritidis vaccines was able to decrease the presence of Salmonella Enteritidis in the birds and in the eggs as well
Chang, Kwang-Hwa; Lai, Chien-Hung; Chen, Shih-Ching; Hsiao, Wen-Tien; Liou, Tsan-Hon; Lee, Chi-Ming
To measure the changes in the total and regional body fat mass, and assess the clinical usefulness of the body mass index (BMI) in detecting overweight subjects with sequelae of poliomyelitis. Prospective, cross-sectional study. General community. Subjects with poliomyelitis (n=17; age range, 42-57y; mean, 47y; 12 men, 5 women) and able-bodied people (n=17) matched by sex, age, body weight, and body height participated in the study. Not applicable. Total and regional body composition was measured with dual-energy x-ray absorptiometry. Clinical characteristics such as blood pressure, serum biochemical studies, and habitual behaviors (daily cigarette smoking, alcohol consumption, and exercise regimen) of all participants were evaluated. Compared with able-bodied controls, subjects with poliomyelitis had a 50% greater total body fat mass, significant increases in the regional fat mass in every part of the body, and had the greatest increase of fat mass in the thorax. Nearly all the subjects (94%) with poliomyelitis were obese according to standards of body composition. However, one third of them had a BMI value of less than 25.0kg/m(2). People with poliomyelitis have a higher prevalence of obesity and a significant increase in total and regional fat mass. Current BMI underestimates the total body fat mass percentage compared with the control; therefore, a population-specific BMI should be used to address the prevalence of obesity in postpolio survivors. Copyright © 2011 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.
Turner, N; Pierse, N; Bissielo, A; Huang, Qs; Radke, S; Baker, Mg; Widdowson, Ma; Kelly, H
This study reports the first vaccine effectiveness (VE) estimates for the prevention of general practice visits and hospitalisations for laboratory-confirmed influenza from an urban population in Auckland, New Zealand, in the same influenza season (2013). A case test-negative design was used to estimate propensity-adjusted VE in both hospital and community settings. Patients with a severe acute respiratory infection (SARI) or influenza-like illness (ILI) were defined as requiring hospitalisation (SARI) or attending a general practice (ILI) with a history of fever or measured temperature ≥38 °C, cough and onset within the past 10 days. Those who tested positive for influenza virus were cases while those who tested negative were controls. Results were analysed to 7 days post symptom onset and adjusted for the propensity to be vaccinated and the timing during the influenza season. Influenza vaccination provided 52% (95% CI: 32 to 66) protection against laboratory-confirmed influenza hospitalisation and 56% (95% CI: 34 to 70) against presenting to general practice with influenza. VE estimates were similar for all types and subtypes. This study found moderate effectiveness of influenza vaccine against medically attended and hospitalised influenza in New Zealand, a temperate, southern hemisphere country during the 2013 winter season.
Báguena Cervellera, María José
Full Text Available Studies into the polio virus began in Valencia in 1959 with the work undertaken by the microbiologist Vicente Sanchis-Bayarri Vaillant. After his education at the Rochester University and at the Pasteur Institute, Sanchis-Bayarri Vaillant established a laboratory of cell cultures at the Faculty of Medicine in Valencia, where he developed a new diagnostic technique for the poliomyelitis virus. In addition, epidemiological studies were carried out both prior to and post the 1963 vaccination campaign, which proved that Sabin’s oral vaccine was both effective and safe for use.
Los estudios sobre el virus de la polio comenzaron en Valencia en 1959 de la mano del microbiólogo Vicente Sanchis-Bayarri Vaillant. Tras su formación en virología en la Universidad de Rochester y en el Instituto Pasteur, puso en marcha un laboratorio de cultivos celulares en la Facultad de Medicina de Valencia, en donde desarrolló una técnica diagnóstica nueva para el virus de la polio. Por otra parte, se llevaron a cabo estudios epidemiológicos antes y después de la campaña de vacunación de 1963, que demostraron la eficacia de la vacuna oral de Sabin y su inocuidad.
Veber, P.; Jurmanova, K.; Lesko, J.; Hana, L.; Veber, V.
Inactivation of mycoplasms in biological materials was achieved using gamma radiation with a dose rate of 1x10 4 to 5x10 6 rads/h for 1 to 250 hours. The technique is advantageous for allowing the inactivation of the final form of products (tablets, vaccines, etc.). (J.P.)
Veronesi, L; Affanni, P; Verrotti di Pianella, C; Colucci, M E; Tanzi, M L
This cross-sectional seroprevalence study was carried out in 2007 to estimate the immunological status associated with poliomyelitis among fertile women , according to demographic changes. We consecutively enrolled 493 healthy mothers at the time of delivery in order to assess immunity against poliomyelitis by a neutralisation inhibition test. Despite the lack of seronegative subjects, our investigation showed low GMTs, which confirmed a reduction in the "booster effect". The GMTs against poliovirus 1, poliovirus 2 and poliovirus 3 were 25.20, 14.79 and 8.80, respectively. The data that emerged from our survey showed that GMTs have decreased significantly since 1983 and reached low-to-medium values over the past 25 years. The serum prevalence studies, together with the vaccination coverage estimates, are useful and are strongly recommended in order to highlight and identify the possible scenarios in which susceptible subject groups may be present simultaneously as well the possibility of the reintroduction of wild virus in an area that was previously free of polio.
Full Text Available The last issue of the report «vaccines and immunization: world situation» stresses considerable success in immunization at the global level since the mid 90 s — completely total eradication of poliomyelitis across the world, as well as the drastic reduction of the new measles and tetanus cases among mothers and newborns in some poor countries. The report also briefly describes the progress in the development and implementation of the new life saving vaccines, which may save millions of lives annually. The authors have explained some of the reasons, why the global community should invest in immunization, as well as the perspectives for the use of vaccines and immunization in future.Key words: vaccine, immunization, children.
Full Text Available Oral poliovirus vaccine (OPV developed by A. Sabin has been effectively used to control poliomyelitis in Brazil, and the last case with the isolation of a wild poliovirus strain occurred in March 1989. Although the vaccine controlled the circulation of wild strains and poliomyelitis cases associated with these strains were not detected during the last eight years, rare cases classified as vaccine-associated paralytic poliomyelitis (VAPP have been detected. Molecular characterization studies of poliovirus strains isolated from VAPP cases and from healthy contacts have confirmed that the isolates are derived from the Sabin vaccine strains and also detected genomic modifications known or suspected to increase neurovirulence such as mutations and recombination. The molecular characterization of polioviruses isolated during the last eight years from paralysis cases classified as Guillain-Barré (GBS syndrome and transverse myelitits (TM, and from facial paralysis (FP cases also confirmed the vaccine origin of the strains and demonstrated mutations known to increase neurovirulence. Analysis of the epidemiologic data of these GBS, TM and FP cases demonstrated that in most of them the last OPV dose was given months or years before the onset of the disease and the isolation of the polioviruses. The temporal association between the isolation of these strains and the GBS, TM and FP suggested that the Sabin vaccine-derived poliovirus strains could also rarely trigger the diseases.
Estado vacinal, tipo de habitação e nível cultural da mãe e sua relação com o estado imunitário à poliomielite, em uma amostra de escolares do município de São Paulo, Brasil Relation of the vaccination status, housing and cultural level of the mother to the immune status to poliomyelitis in a sample of school children from the City of S. Paulo, Brazil
mother - literate or illiterate. These factors were studied in relation to the prevalence of neutralizing antibodies and the immune status to poliomyelitis of those children. The results showed a correlation between the presence of type 1, 2 and 3 poliovirus antibodies and the number of doses of trivalent Sabin vaccine fed to children 7 and 8 years old, who exibited satisfactory immunity level only with 5 and more doses of the vaccine. In the age group of 9 to 15 years and higher, the immune status of the children was no more related to the number of doses of the vaccine which is considered as a result of the immunization of the children by means of natural infections with circulating polioviruses. When the immune status of the children was related to housing and the cultural level of the mother, the relationship described for certain age groups (7 and 8 years was not observed, which seems to be explained by the same reasons refered to the 9 to 15 and higher age groups. The authors recommended that the primary course of immunization for infants should consist of at least 5 doses of trivalent Sabin vaccine.
Sporadic isolation of sabin-like polioviruses and high-level detection of non-polio enteroviruses during sewage surveillance in seven Italian cities, after several years of inactivated poliovirus vaccination.
Battistone, A; Buttinelli, G; Fiore, S; Amato, C; Bonomo, P; Patti, A M; Vulcano, A; Barbi, M; Binda, S; Pellegrinelli, L; Tanzi, M L; Affanni, P; Castiglia, P; Germinario, C; Mercurio, P; Cicala, A; Triassi, M; Pennino, F; Fiore, L
Sewage surveillance in seven Italian cities between 2005 and 2008, after the introduction of inactivated poliovirus vaccination (IPV) in 2002, showed rare polioviruses, none that were wild-type or circulating vaccine-derived poliovirus (cVDPV), and many other enteroviruses among 1,392 samples analyzed. Two of five polioviruses (PV) detected were Sabin-like PV2 and three PV3, based on enzyme-linked immunosorbent assay (ELISA) and PCR results. Neurovirulence-related mutations were found in the 5'noncoding region (5'NCR) of all strains and, for a PV2, also in VP1 region 143 (Ile>Thr). Intertypic recombination in the 3D region was detected in a second PV2 (Sabin 2/Sabin 1) and a PV3 (Sabin 3/Sabin 2). The low mutation rate in VP1 for all PVs suggests limited interhuman virus passages, consistent with efficient polio immunization in Italy. Nonetheless, these findings highlight the risk of wild or Sabin poliovirus reintroduction from abroad. Non-polio enteroviruses (NPEVs) were detected, 448 of which were coxsackievirus B (CVB) and 294 of which were echoviruses (Echo). Fifty-six NPEVs failing serological typing were characterized by sequencing the VP1 region (nucleotides [nt] 2628 to 2976). A total of 448 CVB and 294 Echo strains were identified; among those strains, CVB2, CVB5, and Echo 11 predominated. Environmental CVB5 and CVB2 strains from this study showed high sequence identity with GenBank global strains. The high similarity between environmental NPEVs and clinical strains from the same areas of Italy and the same periods indicates that environmental strains reflect the viruses circulating in the population and highlights the potential risk of inefficient wastewater treatments. This study confirmed that sewage surveillance can be more sensitive than acute flaccid paralysis (AFP) surveillance in monitoring silent poliovirus circulation in the population as well as the suitability of molecular approaches to enterovirus typing.
Turner, N; Pierse, N; Huang, Q S; Radke, S; Bissielo, A; Thompson, M G; Kelly, H
We present preliminary results of influenza vaccine effectiveness (VE) in New Zealand using a case test-negative design for 28 April to 31 August 2014. VE adjusted for age and time of admission among all ages against severe acute respiratory illness hospital presentation due to laboratory-confirmed influenza was 54% (95% CI: 19 to 74) and specifically against A(H1N1)pdm09 was 65% (95% CI:33 to 81). For influenza-confirmed primary care visits, VE was 67% (95% CI: 48 to 79) overall and 73% (95% CI: 50 to 85) against A(H1N1)pdm09.
Gan, Zhi-Wei Jonathan; Pang, Hee Nee
We report our experience with outcomes of poliomyelitis in the Asian population. Sixteen total knee replacements in 14 patients with polio-affected knees were followed up for at least 18 months. Follow-up assessment included scoring with the American Knee Society Score (AKSS), Oxford knee score, and Short Form 36 Health Survey scores. The mean AKSS improved from 25.59 preoperatively to 82.94 at 24 months, with greater improvement in the knee score. The mean Oxford knee score improved from 40.82 preoperatively to 20.53 at 24 months. The mean AKSS pain score rose from 2.35 to 47.66 at 24 months. The Short Form 36 Health Survey physical functioning and bodily pain scores improved for all patients. Primary total knee arthroplasty of poliomyelitis-affected limbs shows good outcomes, improving quality of life, and decreasing pain. Copyright © 2016 Elsevier Inc. All rights reserved.
Zhukova, L I; Rafeenko, G K; Larin, F I; Shcherbina, L I; Shut', I N; Davydova, M A; Vaniukov, A A
Evaluation of epidemic situation by non-poliomyelitis enterovirus infections in Krasnodar region in multi-year dynamics and characterization of clinical course of enterovirus serous meningitis in hospitalize patients. Retrospective analysis of non-poliomyelitis enterovirus infection epidemi process manifestations during 2002-2012 in Krasnodar region territory based on data of Center of Hygien and Epidemiology in Krasnodar Region. Clinical-epidemiologic characteristics of enterovirus infections in Krasnodar region are presented. Landscape ofenteroviruses isolated from the environment of some territories of the region and from the biological material of patients with various diseases is demonstrated. Clinical features ofenterovirus meningitis course are characterized. Enterovirus transmission b contact route was established to be the most frequent. A lack of pathognomonic symptoms and awareness o physicians of various specialties regarding diagnostics of this infection are the clinical problems of non-po liomyelitis enterovirus diseases.
Full Text Available The challenges faced in delivering lifesaving vaccines to the targeted beneficiaries need to be addressed from the existing knowledge and learning from the past. This review documents the history of vaccines and vaccination in India with an objective to derive lessons for policy direction to expand the benefits of vaccination in the country. A brief historical perspective on smallpox disease and preventive efforts since antiquity is followed by an overview of 19 th century efforts to replace variolation by vaccination, setting up of a few vaccine institutes, cholera vaccine trial and the discovery of plague vaccine. The early twentieth century witnessed the challenges in expansion of smallpox vaccination, typhoid vaccine trial in Indian army personnel, and setting up of vaccine institutes in almost each of the then Indian States. In the post-independence period, the BCG vaccine laboratory and other national institutes were established; a number of private vaccine manufacturers came up, besides the continuation of smallpox eradication effort till the country became smallpox free in 1977. The Expanded Programme of Immunization (EPI (1978 and then Universal Immunization Programme (UIP (1985 were launched in India. The intervening events since UIP till India being declared non-endemic for poliomyelitis in 2012 have been described. Though the preventive efforts from diseases were practiced in India, the reluctance, opposition and a slow acceptance of vaccination have been the characteristic of vaccination history in the country. The operational challenges keep the coverage inequitable in the country. The lessons from the past events have been analysed and interpreted to guide immunization efforts.
The challenges faced in delivering lifesaving vaccines to the targeted beneficiaries need to be addressed from the existing knowledge and learning from the past. This review documents the history of vaccines and vaccination in India with an objective to derive lessons for policy direction to expand the benefits of vaccination in the country. A brief historical perspective on smallpox disease and preventive efforts since antiquity is followed by an overview of 19 th century efforts to replace variolation by vaccination, setting up of a few vaccine institutes, cholera vaccine trial and the discovery of plague vaccine. The early twentieth century witnessed the challenges in expansion of smallpox vaccination, typhoid vaccine trial in Indian army personnel, and setting up of vaccine institutes in almost each of the then Indian States. In the post-independence period, the BCG vaccine laboratory and other national institutes were established; a number of private vaccine manufacturers came up, besides the continuation of smallpox eradication effort till the country became smallpox free in 1977. The Expanded Programme of Immunization (EPI) (1978) and then Universal Immunization Programme (UIP) (1985) were launched in India. The intervening events since UIP till India being declared non-endemic for poliomyelitis in 2012 have been described. Though the preventive efforts from diseases were practiced in India, the reluctance, opposition and a slow acceptance of vaccination have been the characteristic of vaccination history in the country. The operational challenges keep the coverage inequitable in the country. The lessons from the past events have been analysed and interpreted to guide immunization efforts.
Garon, Julie R; Cochi, Stephen L; Orenstein, Walter A
In the United States during the 1950's, polio was on the forefront of every provider and caregiver's mind. Today, most providers in the United States have never seen a case. The Global Polio Eradication Initiative (GPEI), which began in 1988 has reduced the number of cases by over 99%. The world is closer to achieving global eradication of polio than ever before but as long as poliovirus circulates anywhere in the world, every country is vulnerable. The global community can support the polio eradication effort through continued vaccination, surveillance, enforcing travel regulations and contributing financial support, partnerships and advocacy. Copyright © 2015 Elsevier Inc. All rights reserved.
Casula, M.; Steentjes, K.; Aronica, E.; van Geel, B. M.; Troost, D.
Post-polio syndrome (PPS) develops in approximately 30% of polio survivors several decades after the acute attack of paralytic poliomyelitis. Some of these patients develop post-poliomyelitis muscular atrophy (PPMA) which is characterized by a slowly progressive muscle weakness. Due to its
Zahorska, R.; Mazur, N.; Korbecki, M.
By means of the antigen extinction limit test it was shown that a triple dose vaccination of guinea pigs with UV-inactivated measles virus gave better results, than a single dose vaccination which was proved by the very low immunogenicity index. For both vaccination schemes (single and triple) the immune response was only sligthly influenced by a change of dose from 10 5 to 10 6 HadU 50 /ml or by the addition of aluminum adjuvant. In the antigen extinction limit test the antibody levels were determined by two methods (HIT and NT) the results of which were statistically equivalent. The UV-inactivated measles virus was also found to induce hemolysis-inhibiting antibodies. (orig.) [de
Ado, J Mohammed; Etsano, Andrew; Shuaib, Faisal; Damisa, Eunice; Mkanda, Pascal; Gasasira, Alex; Banda, Richard; Korir, Charles; Johnson, Ticha; Dieng, Boubacar; Corkum, Melissa; Enemaku, Ogu; Mataruse, Noah; Ohuabunwo, Chima; Baig, Shahzad; Galway, Michael; Seaman, Vincent; Wiesen, Eric; Vertefeuille, John; Ogbuanu, Ikechukwu U; Armstrong, Gregory; Mahoney, Frank J
Transmission of wild poliovirus (WPV) has never been interrupted in Afghanistan, Pakistan, and Nigeria. Since 2003, infections with WPV of Nigerian origin have been detected in 25 polio-free countries. In 2012, the Nigerian government created an emergency operations center and implemented a national emergency action plan to eradicate polio. The 2013 revision of this plan prioritized (1) improving the quality of supplemental immunization activities (SIAs), (2) implementing strategies to reach underserved populations, (3) adopting special approaches in security-compromised areas, (4) improving outbreak response, (5) enhancing routine immunization and activities implemented between SIAs, and (6) strengthening surveillance. This report summarizes implementation of these activities during a period of unprecedented insecurity and violence, including the killing of health workers and the onset of a state of emergency in the northeast zone. This report reviews management strategies, innovations, trends in case counts, vaccination and social mobilization activities, and surveillance and monitoring data to assess progress in polio eradication in Nigeria. Nigeria has made significant improvements in the management of polio eradication initiative (pei) activities with marked improvement in the quality of SIAs, as measured by lot quality assurance sampling (LQAS). Comparing results from February 2012 with results from December 2013, the proportion of local government areas (LGAs) conducting LQAS in the 11 high-risk states at the ≥90% pass/fail threshold increased from 7% to 42%, and the proportion at the 80%-89% threshold increased from 9% to 30%. During January-December 2013, 53 polio cases were reported from 26 LGAs in 9 states in Nigeria, compared with 122 cases reported from 13 states in 2012. No cases of WPV type 3 infection have been reported since November 2012. In 2013, no polio cases due to any poliovirus type were detected in the northwest sanctuaries of Nigeria. In
A clinical trial to assess the immunogenicity and safety of Inactivated Influenza Vaccine (Whole Virion IP (Pandemic Influenza (H1N1 2009 Monovalent Vaccine; VaxiFlu-S ™ in healthy Indian adult population
A H Kubavat
Full Text Available Background : The pandemic of H1N1 2009 influenza has spread world over and low degree of virus transmission has continued in several regions of India. Aims : To assess the immunogenicity and safety of Pandemic Influenza (H1N1 2009 Monovalent Vaccine in healthy adult Indian population. Settings and Design : Prospective, open label, multicentric, phase 2/3 clinical trial. Materials and Methods : Healthy adult Indian subjects belonging to either 18-59 years or ≥60 years age groups were enrolled and administered a single 0.5 ml (≥15 mcg of hemagglutinin antigen dose of vaccine in the deltoid muscle. Anti-hemagglutinin antibody titer was assessed at baseline and 21 (±2 days after vaccination by Hemagglutination Inhibition (HI test. Safety assessments were done for a period of 42 days. Statistical Analysis Used : Percentages of appropriate population with 95% confidence intervals calculated, log transformation of the data to calculate Geometric Mean Titers (GMTs and chi-square test and student′s t-test applied for significance testing. Results : 182/198 and 53/63 volunteers in age groups of 18-59 years and ≥60 years, respectively, achieved an HI titer ≥1 : 40 at Day 21 (91.9% [95% confidence interval: 88.1-95.7%] and 84.1% [75.1-93.2%]; P=0.072. Further, 171/198 and 50/63 volunteers in the respective age groups achieved seroconversion/four-fold increase in titer at Day 21 (86.4% [81.6-91.1%] and 79.4% [69.4-89.4%]; P=0.179. A significant rise of 22.6-fold [18.0-28.4] and 10.5-fold [7.4-15.0] was noted in GMT in the respective age groups (P<0.001 for both groups as compared to baseline. Nine vaccine-related adverse events were reported (3.4% incidence [1.2-5.6%], which were of low severity only. Conclusions : Pandemic Influenza (H1N1 2009 Monovalent Vaccine produces excellent immunogenic response with a good tolerability profile in adult Indian population.
First-in-human safety and immunogenicity investigations of three adjuvanted reduced dose inactivated poliovirus vaccines (IPV-Al SSI) compared to full dose IPV Vaccine SSI when given as a booster vaccination to adolescents with a history of IPV vaccination at 3, 5, 12months and 5years of age.
Lindgren, Line M; Tingskov, Pernille N; Justesen, Annette H; Nedergaard, Bettina S; Olsen, Klaus J; Andreasen, Lars V; Kromann, Ingrid; Sørensen, Charlotte; Dietrich, Jes; Thierry-Carstensen, Birgit
There is a demand of affordable IPV in the World. Statens Serum Institut (SSI) has developed three reduced dose IPV formulations adsorbed to aluminium hydroxide; 1/3 IPV-Al, 1/5 IPV-Al and 1/10 IPV-Al SSI, and now report the results of the first investigations in humans. 240 Danish adolescents, aged 10-15years, and childhood vaccinated with IPV were booster vaccinated with 1/3 IPV-Al, 1/5 IPV-Al, 1/10 IPV-Al or IPV Vaccine SSI. The booster effects (GMTRs) of the three IPV-Al SSI were compared to IPV Vaccine SSI, and evaluated for non-inferiority. The pre-vaccination GMTs were similar across the groups; 926 (type 1), 969 (type 2) and 846 (type 3) in the total trial population. The GMTRs by poliovirus type and IPV formulation were: Type 1: 17.0 (1/3 IPV-Al), 13.0 (1/5 IPV-Al), 7.1 (1/10 IPV-Al) and 42.2 (IPV Vaccine SSI). Type 2: 12.5 (1/3 IPV-Al), 13.1 (1/5 IPV-Al), 7.6 (1/10 IPV-Al) and 47.8 (IPV Vaccine SSI). Type 3: 14.5 (1/3 IPV-Al), 16.2 (1/5 IPV-Al), 8.9 (1/10 IPV-Al) and 62.4 (IPV Vaccine SSI) Thus, the three IPV-Al formulations were highly immunogenic, but inferior to IPV Vaccine SSI, in this booster vaccination trial. No SAE and no AE of severe intensity occurred. 59.2% of the subjects reported at least one AE. Injection site pain was the most frequent AE in all groups; from 24.6% to 43.3%. Injection site redness and swelling frequencies were<5% in most and<10% in all groups. The most frequent systemic AEs were fatigue (from 8.2% to 15.0%) and headache (from 15.0% to 28.3%). Most AEs were of mild intensity. In conclusion, the three IPV-Al SSI were safe in adolescents and the booster effects were satisfactory. ClinicalTrials.gov registration number: NCT02280447. Copyright © 2016. Published by Elsevier Ltd.
Sánchez, Juan Antonio Rodríguez; Santos, Inês Guerra
The change in the social perception of poliomyelitis in the Iberian Peninsula through content analysis of two large-circulation newspapers between 1995 and 2009 is examined. The disappearance from the journalistic agenda of poliomyelitis and people living with the after-effects of the disease led it to be excluded from the public agenda. Poliomyelitis was associated with poverty and ignorance in distant countries that were susceptible to cooperation activities and only came to public attention when it was perceived as a threat to the West, linked to health crises or in a metaphorical sense. Thus, post-poliomyelitis syndrome was barely visible in the Portuguese case and poorly represented in Spain by association.
Safety and immunogenicity of 2010-2011 H1N12009-containing trivalent inactivated influenza vaccine in children 12-59 months of age previously given AS03-adjuvanted H1N12009 pandemic vaccine: a PHAC/CIHR Influenza Research Network (PCIRN) study.
Langley, Joanne M; Scheifele, David W; Quach, Caroline; Vanderkooi, Otto G; Ward, Brian; McNeil, Shelly; Dobson, Simon; Kellner, James D; Kuhn, Susan; Kollman, Tobias; MacKinnon-Cameron, Donna; Smith, Bruce; Li, Yan; Halperin, Scott A
Concern arose in 2010 that reactogenicity, particularly febrile seizures, to influenza A/H1N1-containing 2010-2011 trivalent seasonal inactivated influenza vaccine (TIV) could occur in young children who had been previously immunized and/or infected with the pandemic strain. We conducted a pre-season study of 2010-2011 TIV safety and immunogenicity in children 12-59 months of age to inform public health decision making. Children immunized with 1 or 2 doses of the pandemic vaccine, with or without the 2009-10 TIV, received 1 or 2 doses of 2010-11 TIV in an observational, multicentre Canadian study. Standard safety monitoring was enhanced by a telephone call at ~24 h post-TIV when adverse events were expected to peak. Summary safety reports were rapidly reported to public health before the launch of public programs. TIV immunogenicity was ass