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Sample records for efficacious swine vaccine

  1. Efficacy of Influenza Vaccination and Tamiflu? Treatment ? Comparative Studies with Eurasian Swine Influenza Viruses in Pigs

    OpenAIRE

    Duerrwald, Ralf; Schlegel, Michael; Bauer, Katja; Vissiennon, Th?ophile; Wutzler, Peter; Schmidtke, Michaela

    2013-01-01

    Recent epidemiological developments demonstrated that gene segments of swine influenza A viruses can account for antigenic changes as well as reduced drug susceptibility of pandemic influenza A viruses. This raises questions about the efficacy of preventive measures against swine influenza A viruses. Here, the protective effect of vaccination was compared with that of prophylactic Tamiflu® treatment against two Eurasian swine influenza A viruses. 11-week-old pigs were infected by aerosol nebu...

  2. Third generation DIVA vaccine towards classical swine fever virus. Efficacy in face of maternal immunity

    DEFF Research Database (Denmark)

    Rangelova, Desislava Yordanova

    General purpose and objectives Classical swine fever (CSF) is a highly contagious disease that causes huge economical losses and animal welfare concerns worldwide. Generally, vaccination is an effective and safe method to control the disease. Following vaccination the pig’s immune system develops...... a new DIVA vaccine candidate. The vaccine candidate “CP7E2alf” is intended for either intramuscular vaccination of domestic pig or for bait vaccination of wild boar. In this thesis as part of the clinical testing of the injection vaccine the efficacy of “CP7E2alf” was evaluated in young piglets...

  3. Efficacy of a novel Pasteurella multocida vaccine against progressive atrophic rhinitis of swine

    Science.gov (United States)

    Hsuan, Shih-Ling; Liao, Chih-Ming; Huang, Chienjin; Winton, James R.; Chen, Zeng-Weng; Lee, Wei-Cheng; Liao, Jiunn-Wang; Chen, Ter-Hsin; Chiou, Chwei-Jang; Yeh, Kuang-Sheng; Chien, Maw-Sheng

    2009-01-01

    The efficacy of a novel vaccine composed of three short recombinant subunit Pasteurella multocida toxin (PMT) proteins in combination with a bi-valent P. multocida whole-cell bacterin (rsPMT–PM) was evaluated in field studies for prevention and control of progressive atrophic rhinitis (PAR) of swine at 15 conventional farrow-to-finish farms. Experimental piglets that were immunized twice with the rsPMT–PM vaccine developed detectable titers of neutralizing antibodies (greater than 1:8) that prevented the growth retardation and pathological lesions typically observed following challenge with authentic PMT. A total of 542 sows were vaccinated once or twice prior to parturition and serum neutralizing antibody titers were evaluated. Both single and double vaccination protocols induced neutralizing antibody titers of 1:16 or higher in 62% and 74% of sows, respectively. Notably, neither sows nor piglets at a farm experiencing a severe outbreak of PAR at the time of the vaccination trial had detectable antibody titers, but antibody titers increased significantly to 1:16 or higher in 40% of sows following double vaccination. During the year after vaccination, clinical signs of PAR decreased in fattening pigs and growth performance improved sufficiently to reduce the rearing period until marketing by 2 weeks. Collectively, these results indicate that the rsPMT–PM vaccine could be used to provide protective immunity for controlling the prevalence and severity of PAR among farm-raised swine.

  4. Immunogenicity and efficacy of a rough Brucella suis vaccine delivered orally or parenterally to feral swine

    Science.gov (United States)

    Brucella suis strain 353-1 is a stable vaccine strain that is clinically safe, does not cause positive serologic responses on conventional brucellosis surveillance tests, and induces humoral and cellular immunity in swine after vaccination. In this study, we evaluated tissue clearance and immunologi...

  5. Efficacy of influenza vaccination and tamiflu® treatment--comparative studies with Eurasian Swine influenza viruses in pigs.

    Science.gov (United States)

    Duerrwald, Ralf; Schlegel, Michael; Bauer, Katja; Vissiennon, Théophile; Wutzler, Peter; Schmidtke, Michaela

    2013-01-01

    Recent epidemiological developments demonstrated that gene segments of swine influenza A viruses can account for antigenic changes as well as reduced drug susceptibility of pandemic influenza A viruses. This raises questions about the efficacy of preventive measures against swine influenza A viruses. Here, the protective effect of vaccination was compared with that of prophylactic Tamiflu® treatment against two Eurasian swine influenza A viruses. 11-week-old pigs were infected by aerosol nebulisation with high doses of influenza virus A/swine/Potsdam/15/1981 (H1N1/1981, heterologous challenge to H1N1 vaccine strain) and A/swine/Bakum/1832/2000 (H1N2/2000, homologous challenge to H1N2 vaccine strain) in two independent trials. In each trial (i) 10 pigs were vaccinated twice with a trivalent vaccine (RESPIPORC® FLU3; 28 and 7 days before infection), (ii) another 10 pigs received 150 mg/day of Tamiflu® for 5 days starting 12 h before infection, and (iii) 12 virus-infected pigs were left unvaccinated and untreated and served as controls. Both viruses replicated efficiently in porcine respiratory organs causing influenza with fever, dyspnoea, and pneumonia. Tamiflu® treatment as well as vaccination prevented clinical signs and significantly reduced virus shedding. Whereas after homologous challenge with H1N2/2000 no infectious virus in lung and hardly any lung inflammation were detected, the virus titre was not and the lung pathology was only partially reduced in H1N1/1981, heterologous challenged pigs. Tamiflu® application did not affect these study parameters. In conclusion, all tested preventive measures provided protection against disease. Vaccination additionally prevented virus replication and histopathological changes in the lung of homologous challenged pigs.

  6. Efficacy of influenza vaccination and tamiflu® treatment--comparative studies with Eurasian Swine influenza viruses in pigs.

    Directory of Open Access Journals (Sweden)

    Ralf Duerrwald

    Full Text Available Recent epidemiological developments demonstrated that gene segments of swine influenza A viruses can account for antigenic changes as well as reduced drug susceptibility of pandemic influenza A viruses. This raises questions about the efficacy of preventive measures against swine influenza A viruses. Here, the protective effect of vaccination was compared with that of prophylactic Tamiflu® treatment against two Eurasian swine influenza A viruses. 11-week-old pigs were infected by aerosol nebulisation with high doses of influenza virus A/swine/Potsdam/15/1981 (H1N1/1981, heterologous challenge to H1N1 vaccine strain and A/swine/Bakum/1832/2000 (H1N2/2000, homologous challenge to H1N2 vaccine strain in two independent trials. In each trial (i 10 pigs were vaccinated twice with a trivalent vaccine (RESPIPORC® FLU3; 28 and 7 days before infection, (ii another 10 pigs received 150 mg/day of Tamiflu® for 5 days starting 12 h before infection, and (iii 12 virus-infected pigs were left unvaccinated and untreated and served as controls. Both viruses replicated efficiently in porcine respiratory organs causing influenza with fever, dyspnoea, and pneumonia. Tamiflu® treatment as well as vaccination prevented clinical signs and significantly reduced virus shedding. Whereas after homologous challenge with H1N2/2000 no infectious virus in lung and hardly any lung inflammation were detected, the virus titre was not and the lung pathology was only partially reduced in H1N1/1981, heterologous challenged pigs. Tamiflu® application did not affect these study parameters. In conclusion, all tested preventive measures provided protection against disease. Vaccination additionally prevented virus replication and histopathological changes in the lung of homologous challenged pigs.

  7. Efficacy of Influenza Vaccination and Tamiflu® Treatment – Comparative Studies with Eurasian Swine Influenza Viruses in Pigs

    Science.gov (United States)

    Duerrwald, Ralf; Schlegel, Michael; Bauer, Katja; Vissiennon, Théophile; Wutzler, Peter; Schmidtke, Michaela

    2013-01-01

    Recent epidemiological developments demonstrated that gene segments of swine influenza A viruses can account for antigenic changes as well as reduced drug susceptibility of pandemic influenza A viruses. This raises questions about the efficacy of preventive measures against swine influenza A viruses. Here, the protective effect of vaccination was compared with that of prophylactic Tamiflu® treatment against two Eurasian swine influenza A viruses. 11-week-old pigs were infected by aerosol nebulisation with high doses of influenza virus A/swine/Potsdam/15/1981 (H1N1/1981, heterologous challenge to H1N1 vaccine strain) and A/swine/Bakum/1832/2000 (H1N2/2000, homologous challenge to H1N2 vaccine strain) in two independent trials. In each trial (i) 10 pigs were vaccinated twice with a trivalent vaccine (RESPIPORC® FLU3; 28 and 7 days before infection), (ii) another 10 pigs received 150 mg/day of Tamiflu® for 5 days starting 12 h before infection, and (iii) 12 virus-infected pigs were left unvaccinated and untreated and served as controls. Both viruses replicated efficiently in porcine respiratory organs causing influenza with fever, dyspnoea, and pneumonia. Tamiflu® treatment as well as vaccination prevented clinical signs and significantly reduced virus shedding. Whereas after homologous challenge with H1N2/2000 no infectious virus in lung and hardly any lung inflammation were detected, the virus titre was not and the lung pathology was only partially reduced in H1N1/1981, heterologous challenged pigs. Tamiflu® application did not affect these study parameters. In conclusion, all tested preventive measures provided protection against disease. Vaccination additionally prevented virus replication and histopathological changes in the lung of homologous challenged pigs. PMID:23630601

  8. Efficacy of chimeric Pestivirus vaccine candidates against classical swine fever: protection and DIVA characteristics.

    Science.gov (United States)

    Eblé, P L; Geurts, Y; Quak, S; Moonen-Leusen, H W; Blome, S; Hofmann, M A; Koenen, F; Beer, M; Loeffen, W L A

    2013-03-23

    Currently no live DIVA (Differentiating Infected from Vaccinated Animals) vaccines against classical swine fever (CSF) are available. The aim of this study was to investigate whether chimeric pestivirus vaccine candidates (CP7_E2alf, Flc11 and Flc9) are able to protect pigs against clinical signs, and to reduce virus shedding and virus transmission, after a challenge with CSF virus (CSFV), 7 or 14 days after a single intramuscular vaccination. In these vaccine candidates, either the E2 or the E(rns) encoding genome region of a bovine viral diarrhoea virus strain were combined with a cDNA copy of CSFV or vice versa. Furthermore, currently available serological DIVA tests were evaluated. The vaccine candidates were compared to the C-strain. All vaccine candidates protected against clinical signs. No transmission to contact pigs was detected in the groups vaccinated with C-strain, CP7_E2alf and Flc11. Limited transmission occurred in the groups vaccinated with Flc9. All vaccine candidates would be suitable to stop on-going transmission of CSFV. For Flc11, no reliable differentiation was possible with the current E(rns)-based DIVA test. For CP7_E2alf, the distribution of the inhibition percentages was such that up to 5% false positive results may be obtained in a large vaccinated population. For Flc9 vaccinated pigs, the E2 ELISA performed very well, with an expected 0.04% false positive results in a large vaccinated population. Both CP7_E2alf and Flc9 are promising candidates to be used as live attenuated marker vaccines against CSF, with protection the best feature of CP7_E2alf, and the DIVA principle the best feature of Flc9. Copyright © 2012 Elsevier B.V. All rights reserved.

  9. Efficacy of a pandemic (H1N1) 2009 virus vaccine in pigs against the pandemic influenza virus is superior to commercially available swine influenza vaccines.

    Science.gov (United States)

    Loeffen, W L A; Stockhofe, N; Weesendorp, E; van Zoelen-Bos, D; Heutink, R; Quak, S; Goovaerts, D; Heldens, J G M; Maas, R; Moormann, R J; Koch, G

    2011-09-28

    In April 2009 a new influenza A/H1N1 strain, currently named "pandemic (H1N1) influenza 2009" (H1N1v), started the first official pandemic in humans since 1968. Several incursions of this virus in pig herds have also been reported from all over the world. Vaccination of pigs may be an option to reduce exposure of human contacts with infected pigs, thereby preventing cross-species transfer, but also to protect pigs themselves, should this virus cause damage in the pig population. Three swine influenza vaccines, two of them commercially available and one experimental, were therefore tested and compared for their efficacy against an H1N1v challenge. One of the commercial vaccines is based on an American classical H1N1 influenza strain, the other is based on a European avian H1N1 influenza strain. The experimental vaccine is based on reassortant virus NYMC X179A (containing the hemagglutinin (HA) and neuraminidase (NA) genes of A/California/7/2009 (H1N1v) and the internal genes of A/Puerto Rico/8/34 (H1N1)). Excretion of infectious virus was reduced by 0.5-3 log(10) by the commercial vaccines, depending on vaccine and sample type. Both vaccines were able to reduce virus replication especially in the lower respiratory tract, with less pathological lesions in vaccinated and subsequently challenged pigs than in unvaccinated controls. In pigs vaccinated with the experimental vaccine, excretion levels of infectious virus in nasal and oropharyngeal swabs, were at or below 1 log(10)TCID(50) per swab and lasted for only 1 or 2 days. An inactivated vaccine containing the HA and NA of an H1N1v is able to protect pigs from an infection with H1N1v, whereas swine influenza vaccines that are currently available are of limited efficaciousness. Whether vaccination of pigs against H1N1v will become opportune remains to be seen and will depend on future evolution of this strain in the pig population. Close monitoring of the pig population, focussing on presence and evolution of

  10. Classical swine fever vaccines-State-of-the-art.

    Science.gov (United States)

    Blome, Sandra; Moß, Claudia; Reimann, Ilona; König, Patricia; Beer, Martin

    2017-07-01

    Due to its impact on animal health and pig industry, classical swine fever (CSF) is still one of the most important viral diseases of pigs. To control the disease, safe and highly efficacious live attenuated vaccines exist for decades. These vaccines have usually outstanding efficacy and safety but lack differentiability of infected from vaccinated animals (DIVA or marker strategy). In contrast, the first generation of E2 subunit marker vaccines shows constraints in efficacy, application, and production. To overcome these limitations, new generations of marker vaccines are developed. A wide range of approaches have been tried including recombinant vaccines, recombinant inactivated vaccines or subunit vaccines, vector vaccines, and DNA/RNA vaccines. During the last years, especially attenuated deletion vaccines or chimeric constructs have shown potential. At present, especially two new constructs have been intensively tested, the adenovirus-delivered, Semliki Forest virus replicon-vectored marker vaccine candidate "rAdV-SFV-E2" and the pestivirus chimera "CP7_E2alf". The later was recently licensed by the European Medicines Agency. Under field conditions, all marker vaccines have to be accompanied by a potent test system. Particularly this point shows still weaknesses and it is important to embed vaccination in a well-established vaccination strategy and a suitable diagnostic workflow. In summary, conventional vaccines are a standard in terms of efficacy. However, only vaccines with DIVA will allow improved eradication strategies e.g. also under emergency vaccination conditions in free regions. To answer this demand, new generations of marker vaccines have been developed and add now to the tool box of CSF control. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. 9 CFR 85.6 - Interstate movement of pseudorabies vaccinate swine, except swine from qualified negative gene...

    Science.gov (United States)

    2010-01-01

    ... vaccinate swine, except swine from qualified negative gene-altered vaccinated herds, not known to be..., except swine from qualified negative gene-altered vaccinated herds, not known to be infected with or exposed to pseudorabies. Pseudorabies vaccinate swine, except swine from qualified negative gene-altered...

  12. African Swine Fever Virus Biology and Vaccine Approaches.

    Science.gov (United States)

    Revilla, Yolanda; Pérez-Núñez, Daniel; Richt, Juergen A

    2018-01-01

    African swine fever (ASF) is an acute and often fatal disease affecting domestic pigs and wild boar, with severe economic consequences for affected countries. ASF is endemic in sub-Saharan Africa and the island of Sardinia, Italy. Since 2007, the virus emerged in the republic of Georgia, and since then spread throughout the Caucasus region and Russia. Outbreaks have also been reported in Belarus, Ukraine, Lithuania, Latvia, Estonia, Romania, Moldova, Czech Republic, and Poland, threatening neighboring West European countries. The causative agent, the African swine fever virus (ASFV), is a large, enveloped, double-stranded DNA virus that enters the cell by macropinocytosis and a clathrin-dependent mechanism. African Swine Fever Virus is able to interfere with various cellular signaling pathways resulting in immunomodulation, thus making the development of an efficacious vaccine very challenging. Inactivated preparations of African Swine Fever Virus do not confer protection, and the role of antibodies in protection remains unclear. The use of live-attenuated vaccines, although rendering suitable levels of protection, presents difficulties due to safety and side effects in the vaccinated animals. Several African Swine Fever Virus proteins have been reported to induce neutralizing antibodies in immunized pigs, and vaccination strategies based on DNA vaccines and recombinant proteins have also been explored, however, without being very successful. The complexity of the virus particle and the ability of the virus to modulate host immune responses are most likely the reason for this failure. Furthermore, no permanent cell lines able to sustain productive virus infection by both virulent and naturally attenuated African Swine Fever Virus strains exist so far, thus impairing basic research and the commercial production of attenuated vaccine candidates. © 2018 Elsevier Inc. All rights reserved.

  13. Protective efficacy of an inactivated Eurasian avian-like H1N1 swine influenza vaccine against homologous H1N1 and heterologous H1N1 and H1N2 viruses in mice.

    Science.gov (United States)

    Sui, Jinyu; Yang, Dawei; Qiao, Chuanling; Xu, Huiyang; Xu, Bangfeng; Wu, Yunpu; Yang, Huanliang; Chen, Yan; Chen, Hualan

    2016-07-19

    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.

  14. Optimal Use of Vaccines for Control of Influenza A Virus in Swine

    Directory of Open Access Journals (Sweden)

    Matthew R. Sandbulte

    2015-01-01

    Full Text Available Influenza A virus in swine (IAV-S is one of the most important infectious disease agents of swine in North America. In addition to the economic burden of IAV-S to the swine industry, the zoonotic potential of IAV-S sometimes leads to serious public health concerns. Adjuvanted, inactivated vaccines have been licensed in the United States for over 20 years, and there is also widespread usage of autogenous/custom IAV-S vaccines. Vaccination induces neutralizing antibodies and protection against infection with very similar strains. However, IAV-S strains are so diverse and prone to mutation that these vaccines often have disappointing efficacy in the field. This scientific review was developed to help veterinarians and others to identify the best available IAV-S vaccine for a particular infected herd. We describe key principles of IAV-S structure and replication, protective immunity, currently available vaccines, and vaccine technologies that show promise for the future. We discuss strategies to optimize the use of available IAV-S vaccines, based on information gathered from modern diagnostics and surveillance programs. Improvements in IAV-S immunization strategies, in both the short term and long term, will benefit swine health and productivity and potentially reduce risks to public health.

  15. Efficacy of a pandemic (H1N1) 2009 virus vaccine in pigs against the pandemic influenza virus is superior to commercially available swine influenza vaccines.

    NARCIS (Netherlands)

    Loeffen, W.L.A.; Stockhofe-Zurwieden, N.; Weesendorp, E.; Zoelen-Bos, van D.J.; Heutink, R.; Quak, J.; Goovaerts, D.; Heldens, J.; Maas, H.A.; Moormann, R.J.M.; Koch, G.

    2011-01-01

    In April 2009 a new influenza A/H1N1 strain, currently named “pandemic (H1N1) influenza 2009¿ (H1N1v), started the first official pandemic in humans since 1968. Several incursions of this virus in pig herds have also been reported from all over the world. Vaccination of pigs may be an option to

  16. Use of inactivated E.Coli enterotoxins to enhance respiratory mucosal adjuvanticity during vaccination in swine

    Science.gov (United States)

    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...

  17. Cross-protective efficacy of engineering serotype A foot-and-mouth disease virus vaccine against the two pandemic strains in swine.

    Science.gov (United States)

    Zheng, Haixue; Lian, Kaiqi; Yang, Fan; Jin, Ye; Zhu, Zixiang; Guo, Jianhong; Cao, Weijun; Liu, Huanan; He, Jijun; Zhang, Keshan; Li, Dan; Liu, Xiangtao

    2015-10-26

    Foot-and-mouth disease (FMD) is a highly contagious vesicular disease that affects domestic and wild cloven-hoofed animals worldwide. Recently, a series of outbreaks of type A FMDV occurred in Southeast Asian countries, China, the Russia Federation, Mongolia, Kazakhstan and South Korea. The FMD virus (A/GDMM/CHA/2013) from China's Guangdong province (2013) is representative of those responsible for the latest epidemic, and has low amino acid identity (93.9%) in VP1 protein with the epidemic strain A/WH/CHA/09 from Wuhan, China in 2009. Both of isolates belong to the Sea-97 genotype of ASIA topotype. Therefore, the application of a new vaccine strain with cross-protective efficacy is of fundamental importance to control the spread of the two described pandemic strains. A chimeric strain rA/P1-FMDV constructed by our lab previously through replacing the P1 gene in the vaccine strain O/CHA/99 with that from the epidemic stain A/WH/CHA/09, has been demonstrated to exhibit good growth characteristics in culture, and the rA/P1-FMDV inactivated vaccine can provide protection against epidemic strain A/WH/CHA/09 in cattle. However, it is still unclear whether the vaccine produces efficient protection against the new pandemic strain (A/GDMM/CHA/2013). Here, vaccine matching and pig 50% protective dose (PD50) tests were performed to assess the vaccine potency. The vaccine matching test showed cross-reactivity of sera from full dose vaccine vaccinated pigs with A/WH/CHA/09 and A/GDMM/CHA/2013 isolates, with average r1 values of 0.94±0.12 and 0.68±0.06 (r1≥0.3), which indicates that the rA/P1-FMDV vaccine is likely to confer good cross-protection against the two isolates. When challenged with two pandemic isolates A/WH/CHA/09 and A/GDMM/CHA/2013 strain, the vaccine achieved 12.51 PD50 and 10.05 PD50 per dose (2.8μg), respectively. The results indicated that the rA/P1-FMDV inactivated vaccine could protect pigs against both A/WH/CHA/09 and A/GDMM/CHA/2013 pandemic isolates

  18. Swine influenza virus: zoonotic potential and vaccination strategies for the control of avian and swine influenzas.

    Science.gov (United States)

    Thacker, Eileen; Janke, Bruce

    2008-02-15

    Influenza viruses are able to infect humans, swine, and avian species, and swine have long been considered a potential source of new influenza viruses that can infect humans. Swine have receptors to which both avian and mammalian influenza viruses bind, which increases the potential for viruses to exchange genetic sequences and produce new reassortant viruses in swine. A number of genetically diverse viruses are circulating in swine herds throughout the world and are a major cause of concern to the swine industry. Control of swine influenza is primarily through the vaccination of sows, to protect young pigs through maternally derived antibodies. However, influenza viruses continue to circulate in pigs after the decay of maternal antibodies, providing a continuing source of virus on a herd basis. Measures to control avian influenza in commercial poultry operations are dictated by the virulence of the virus. Detection of a highly pathogenic avian influenza (HPAI) virus results in immediate elimination of the flock. Low-pathogenic avian influenza viruses are controlled through vaccination, which is done primarily in turkey flocks. Maintenance of the current HPAI virus-free status of poultry in the United States is through constant surveillance of poultry flocks. Although current influenza vaccines for poultry and swine are inactivated and adjuvanted, ongoing research into the development of newer vaccines, such as DNA, live-virus, or vectored vaccines, is being done. Control of influenza virus infection in poultry and swine is critical to the reduction of potential cross-species adaptation and spread of influenza viruses, which will minimize the risk of animals being the source of the next pandemic.

  19. Rheumatoid arthritis and Swine influenza vaccine: a case report.

    Science.gov (United States)

    Basra, Gurjot; Jajoria, Praveen; Gonzalez, Emilio

    2012-01-01

    Rheumatoid arthritis (RA) is the most common chronic inflammatory joint disease. Multiple scientific articles have documented that vaccinations for influenza, MMR, and HBV, to name a few, could be triggers of RA in genetically predisposed individuals. However, there is limited data regarding the association of swine flu vaccine (H1N1) and RA. We report the case of a Mexican American female who developed RA right after vaccination with H1N1 vaccine. Genetically, RA has consistently been associated with an epitope in the third hypervariable region of the HLA-DR β chains, known as the "shared epitope", which is found primarily in DR4 and DR1 regions. The presence of HLA-DRB1 alleles is associated with susceptibility to RA in Mexican Americans. Hence, certain individuals with the presence of the "shared epitope" may develop RA following specific vaccinations. To our knowledge, this is the first reported case of RA following vaccination with the swine flu vaccine.

  20. Rheumatoid Arthritis and Swine Influenza Vaccine: A Case Report

    Directory of Open Access Journals (Sweden)

    Gurjot Basra

    2012-01-01

    Full Text Available Rheumatoid arthritis (RA is the most common chronic inflammatory joint disease. Multiple scientific articles have documented that vaccinations for influenza, MMR, and HBV, to name a few, could be triggers of RA in genetically predisposed individuals. However, there is limited data regarding the association of swine flu vaccine (H1N1 and RA. We report the case of a Mexican American female who developed RA right after vaccination with H1N1 vaccine. Genetically, RA has consistently been associated with an epitope in the third hypervariable region of the HLA-DR chains, known as the “shared epitope”, which is found primarily in DR4 and DR1 regions. The presence of HLA-DRB1 alleles is associated with susceptibility to RA in Mexican Americans. Hence, certain individuals with the presence of the “shared epitope” may develop RA following specific vaccinations. To our knowledge, this is the first reported case of RA following vaccination with the swine flu vaccine.

  1. Novel Vaccine Against Mycoplasma Hyosynoviae: The Immunogenic Effect of Iscom-Based Vaccines in Swine

    DEFF Research Database (Denmark)

    Lauritsen, Klara Tølbøll; Vinther Heydenreich, Annette; Riber, Ulla

    Arthritis in swine is frequently caused by Mycoplasma hyosynoviae (Mhs). For the development of an effective vaccine we investigated the immunogenic effect of three vaccine preparations with the ISCOM adjuvant Posintro™ from Nordic Vaccine. A: formalin fixed whole-cells Mhs (300 µg/dose) mixed...... with Posintro, B: Deoxycholate extracted lipoproteins from Mhs organisms (DOC-antigen, 300 μg/dose) in Posintro and C: DOC-antigen (50 μg/dose) in Posintro. Each vaccine-group contained three pigs. Vaccinations (i.m.) were performed at 12 and 15 weeks of age. The development of specific IgG and secretion...... of IFNγ were measured. Three weeks after the second vaccination, pigs were euthanised and autopsied. Vaccine B induced a high level of specific serum IgG in all pigs a week after boost. Vaccine C gave a variable response after boost, with two pigs seroconverting, while no response was seen by vaccine A...

  2. Microneedle Vaccination Elicits Superior Protection and Antibody Response over Intranasal Vaccination against Swine-Origin Influenza A (H1N1 in Mice.

    Directory of Open Access Journals (Sweden)

    Ju-Hyung Shin

    Full Text Available Influenza is one of the critical infectious diseases globally and vaccination has been considered as the best way to prevent. In this study, immunogenicity and protection efficacy between intranasal (IN and microneedle (MN vaccination was compared using inactivated swine-origin influenza A/H1N1 virus vaccine. Mice were vaccinated by MN or IN administration with 1 μg of inactivated H1N1 virus vaccine. Antigen-specific antibody responses and hemagglutination-inhibition (HI titers were measured in all immunized sera after immunization. Five weeks after an immunization, a lethal challenge was performed to evaluate the protective efficacy. Furthermore, mice were vaccinated by IN administration with higher dosages (> 1 μg, analyzed in the same manner, and compared with 1 μg-vaccine-coated MN. Significantly higher antigen-specific antibody responses and HI titer were measured in sera in MN group than those in IN group. While 100% protection, slight weight loss, and reduced viral replication were observed in MN group, 0% survival rate were observed in IN group. As vaccine dose for IN vaccination increased, MN-immunized sera showed much higher antigen-specific antibody responses and HI titer than other IN groups. In addition, protective immunity of 1 μg-MN group was similar to those of 20- and 40 μg-IN groups. We conclude that MN vaccination showed more potential immune response and protection than IN vaccination at the same vaccine dosage.

  3. Classical Swine Fever Outbreak after Modified Live LOM Strain Vaccination in Naive Pigs, South Korea

    Science.gov (United States)

    Je, Sang H.; Kwon, Taeyong; Yoo, Sung J.; Lee, Dong-Uk; Lee, SeungYoon; Richt, Juergen A.

    2018-01-01

    We report classical swine fever outbreaks occurring in naive pig herds on Jeju Island, South Korea, after the introduction of the LOM vaccine strain. Two isolates from sick pigs had >99% identity with the vaccine stain. LOM strain does not appear safe; its use in the vaccine should be reconsidered. PMID:29553332

  4. 76 FR 79203 - Prospective Grant of Exclusive License: Veterinary Biological Products for Swine Influenza Vaccines

    Science.gov (United States)

    2011-12-21

    ... Exclusive License: Veterinary Biological Products for Swine Influenza Vaccines AGENCY: National Institutes....7. The invention relates to compositions and methods of use as Veterinary Influenza Vaccines... to humans. This technology describes DNA vaccines against influenza serotypes H5N1, H1N1, H3N2, and...

  5. Oronasal and intramuscular vaccination of swine with a modified live porcine parvovirus vaccine: multiplication and transmission of the vaccine virus.

    Science.gov (United States)

    Paul, P S; Mengeling, W L

    1984-12-01

    An attenuated strain NADL-2 of porcine parvovirus (PPV) has been used at the 54th cell culture passage as a modified live-virus (MLV) vaccine. The present study was conducted to determine the minimum immunizing dose of MLV, the extent of MLV multiplication in swine tissues, and its transmission from swine administered MLV oronasally or intramuscularly. Immune response to MLV was dose dependent and swine responded to as little as 10(2) median cell-culture infective doses (CCID50). A 10(5) CCID50 of MLV, the largest dose given, induced the best immune response and was used in subsequent experiments. Route of MLV administration also was found to be important. The MLV replicated in tissues of swine after IM inoculation; however, viral antigen in tissues was less, as measured by immunofluorescence, and serum hemagglutination-inhibition titers for PPV were lower in MLV-inoculated swine than we have previously observed in virulent PPV-inoculated swine. In contrast, oronasal inoculation with MLV did not consistently result in infection of pigs; only 5 of 23 swine had virologic and/or serologic evidence of infection. Virus transmission studies indicated that MLV is shed in feces, but shedding occurs later than that in virulent-PPV-inoculated swine and is inconsistent. Delayed transmission of MLV was observed in contact pigs, which were seronegative at 2 weeks, but became seropositive at 4 weeks--indicating that perhaps a virus population capable of infecting pigs by oronasal route was selected by passage through the pig.(ABSTRACT TRUNCATED AT 250 WORDS)

  6. 76 FR 81467 - Availability of an Environmental Assessment for Field Testing Swine Influenza Vaccine, RNA

    Science.gov (United States)

    2011-12-28

    ...] Availability of an Environmental Assessment for Field Testing Swine Influenza Vaccine, RNA AGENCY: Animal and... Vaccine, RNA. The environmental assessment, which is based on a risk analysis prepared to assess the risks...: Send your comment to Docket No. APHIS-2011-0114, Regulatory Analysis and Development, PPD, APHIS...

  7. Investigations of significance of vaccination against swine parvovirosis in persistently infected sows

    Directory of Open Access Journals (Sweden)

    Lupulović Diana

    2007-01-01

    Full Text Available Parvoviral infection of swine is a disease which is manifested in reproductive disorders in sows and gilts in the form of anestria, premature births, miscarriages, mummified fetuses, the birth of poorly vital piglets and/or a reduced number of piglets in the litter. The infection is present in farms with intensive breeding conditions in the form of an endemic infection, all over the world, and also in our country. Timely diagnostics and adequate prophylaxis prevent the occurrence and spread of this disease. Experimental investigations covered 21 sows, divided into two experimental and a third, the control, group. Animals of the first experimental group were vaccinated once before exposure to the boar using an inactivated vaccine, Porcilis Parvo, and animals of the second experimental group were vaccinated twice at an interval of 3 weeks, also using an inactivated vaccine, Parvovax. Sows of the control group were not vaccinated. Blood samples were taken from all animals four times during the course of the experiment, and specific antibodies against the swine parvovirus were determined using the method of hemagglutination inhibition (HI test. The results of the investigations indicate that there was an increase in the titre of specific antibodies following the vaccination of persistently infected sows with the swine parvivirus, and that the present antibodies did not prevent the creating of an immune response. It was established following a comparison of the geometric mean values of antibody titres of vaccinated sows that there was a significant increase in the antibody level following the two vaccinations using the Parvovax vaccine, against the titre values in sows vaccinated once with the Porcilis Parvo vaccine. In control animals, the average value of the antibody level was many times lower in comparison with the established values in the experimental groups. This provides justification for the implementation of immunoprophylaxis against swine

  8. A novel alphavirus replicon-vectored vaccine delivered by adenovirus induces sterile immunity against classical swine fever.

    Science.gov (United States)

    Sun, Yuan; Li, Hong-Yu; Tian, Da-Yong; Han, Qiu-Ying; Zhang, Xin; Li, Na; Qiu, Hua-Ji

    2011-10-26

    Low efficacy of gene-based vaccines due to inefficient gene delivery and expression has been major bottleneck of their applications. Efforts have been made to improve the efficacy, such as gene gun and electroporation, but the strategies are difficult to put into practical use. In this study, we developed and evaluated an adenovirus-delivered, alphavirus replicon-vectored vaccine (chimeric vector-based vaccine) expressing the E2 gene of classical swine fever virus (CSFV) (rAdV-SFV-E2). Rabbits immunized with rAdV-SFV-E2 developed CSFV-specific antibodies as early as 9 days and as long as 189 days and completely protected from challenge with C-strain. Pigs immunized with rAdV-SFV-E2 (n=5) developed robust humoral and cell-mediated responses to CSFV and were completely protected from subsequent lethal CSFV infection clinically and virologically. The level of immunity and protection induced by rAdV-SFV-E2 was comparable to that provided by the currently used live attenuated vaccine, C-strain. In contrast, both the conventional alphavirus replicon-vectored vaccine pSFV1CS-E2 and conventional adenovirus-vectored vaccine rAdV-E2 provided incomplete protection. The chimeric vector-based vaccine represents the first gene-based vaccine that is able to confer sterile immunity and complete protection against CSFV. The new-concept vaccination strategy may also be valuable in vaccine development against other pathogens. Copyright © 2011 Elsevier Ltd. All rights reserved.

  9. Finding a new drug and vaccine for emerging swine flu: What is the concept?

    Directory of Open Access Journals (Sweden)

    Viroj Wiwanitkit

    2009-08-01

    Full Text Available Viroj WiwanitkitWiwanitkit House, Bangkhae, Bangkok 10160Abstract: Influenza is a well known infection of the respiratory system. The main clinical manifestations of influenza include fever, sore throat, headache, cough, coryza, and malaise. Apart from the well known classical influenza, there are also groups of influenza virus infections that are called “atypical infection”. These infections are usually due to a novel influenza virus infection. In early 2009, an emerging novel influenza originating from Mexico called swine flu was reported. The World Health Organization noted a level VI precaution, the highest level precaution possible, for this newest influenza virus infection. As of June 2009, it is not known if this disease will be successfully controlled. Finding new drugs and vaccine for the emerging swine flu is still required to cope with this emerging worldwide problem.Keywords: swine flu, drug, vaccine, concept

  10. Swine influenza virus vaccines: to change or not to change-that's the question.

    Science.gov (United States)

    Van Reeth, Kristien; Ma, Wenjun

    2013-01-01

    Commercial vaccines currently available against swine influenza virus (SIV) are inactivated, adjuvanted, whole virus vaccines, based on H1N1 and/or H3N2 and/or H1N2 SIVs. In keeping with the antigenic and genetic differences between SIVs circulating in Europe and the US, the vaccines for each region are produced locally and contain different strains. Even within a continent, there is no standardization of vaccine strains, and the antigen mass and adjuvants can also differ between different commercial products. Recombinant protein vaccines against SIV, vector, and DNA vaccines, and vaccines attenuated by reverse genetics have been tested in experimental studies, but they have not yet reached the market. In this review, we aim to present a critical analysis of the performance of commercial inactivated and novel generation SIV vaccines in experimental vaccination challenge studies in pigs. We pay special attention to the differences between commercial SIV vaccines and vaccination attitudes in Europe and in North America, to the issue of vaccine strain selection and changes, and to the potential advantages of novel generation vaccines over the traditional killed SIV vaccines.

  11. Classical swine fever (CSF) marker vaccine - Trial I. Challenge studies in weaner pigs

    DEFF Research Database (Denmark)

    Uttenthal, Åse; Le Potier, M.F.; Romero, L.

    2001-01-01

    , -10 or -7, and subsequently challenged at day 0. The challenge virus was CSFV 277, originating from a recent outbreak of classical swine fever (CSF) in Germany. In all groups, only 5 out of 10 pigs were challenged; the remaining 5 pigs served as vaccinated contact controls. Also, three control groups...

  12. Immuogenicity and safety of a natural rough mutant of Brucella suis as a vaccine for swine

    Science.gov (United States)

    The objective of the current study was to evaluate the safety, immunogenicity and clearance of the natural rough mutant of Brucella suis strain 353-1 (353-1) as a vaccine in domestic swine. In three studies encompassing 155 animals, pigs were inoculated with 353-1 by conjunctival (5 x 10**7 CFU), p...

  13. Approaches and Perspectives for Development of African Swine Fever Virus Vaccines

    Directory of Open Access Journals (Sweden)

    Marisa Arias

    2017-10-01

    Full Text Available African swine fever (ASF is a complex disease of swine, caused by a large DNA virus belonging to the family Asfarviridae. The disease shows variable clinical signs, with high case fatality rates, up to 100%, in the acute forms. ASF is currently present in Africa and Europe where it circulates in different scenarios causing a high socio-economic impact. In most affected regions, control has not been effective in part due to lack of a vaccine. The availability of an effective and safe ASFV vaccines would support and enforce control–eradication strategies. Therefore, work leading to the rational development of protective ASF vaccines is a high priority. Several factors have hindered vaccine development, including the complexity of the ASF virus particle and the large number of proteins encoded by its genome. Many of these virus proteins inhibit the host’s immune system thus facilitating virus replication and persistence. We review previous work aimed at understanding ASFV–host interactions, including mechanisms of protective immunity, and approaches for vaccine development. These include live attenuated vaccines, and “subunit” vaccines, based on DNA, proteins, or virus vectors. In the shorter to medium term, live attenuated vaccines are the most promising and best positioned candidates. Gaps and future research directions are evaluated.

  14. [Human papillomavirus vaccine. Efficacy and safety].

    Science.gov (United States)

    Bruni, Laia; Serrano, Beatriz; Bosch, Xavier; Castellsagué, Xavier

    2015-05-01

    Human papillomavirus (HPV) related disease remains a major cause of morbidity and mortality worldwide. Prophylactic vaccines have been recognized as the most effective intervention to control for HPV-related diseases. This article reviews the major phaseii/iii trials of the bivalent (HPVs16/18), quadrivalent (HPVs6/11/16/18), and the recently approved 9-valent vaccine (HPVs6/11/16/18/31/33/45/52/58). Large trials have been conducted showing the safety, immunogenicity and high efficacy of the bivalent and quadrivalent vaccines in the prevention of pre-invasive lesions and infection, especially when administered at young ages before exposure to HPV. Trials of the 9-valent vaccine have also demonstrated the safety, immunogenicity and efficacy of the vaccine in the prevention of infection and disease associated with the vaccine types, and its potential to substantially increase the overall prevention of HPV-related diseases. Post-licensure country reports have shown the recent and early impact of these vaccines at population level after the implementation of established HPV vaccination programs, including decreases in the prevalence of vaccine HPV types, the incidence of genital warts, and the incidence of high-grade cervical abnormalities. If widely implemented, current HPV vaccines may drastically reduce the incidence of cervical cancer and other HPV-related cancers and diseases. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  15. Accelerating vaccine development for African swine fever virus ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    2018-01-12

    Jan 12, 2018 ... Engineering a wild fast-growing Mycoplasma bacterium to generate a novel vaccine for contagious caprine ... Engineering vaccines against hemorrhagic septicemia in ruminants ... Solutions. Careers · Contact Us · Site map.

  16. Accelerating vaccine development for African swine fever virus ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Photo: IDRC / Bartay The challenge African swine fever (ASF) is a highly infectious hemorrhagic viral disease that wipes out entire herds of infected pigs. ASF is widespread in at least half of sub-Saharan Africa, and threatens food security due to devastating economic losses.

  17. Meta-analysis on the efficacy of foot-and-mouth disease emergency vaccination

    DEFF Research Database (Denmark)

    Hisham Beshara Halasa, Tariq; Boklund, Anette; Cox, Sarah

    2011-01-01

    the results. Peer-reviewed, symposium, and unpublished studies were considered in the analysis. Clinical protection and virological protection against foot and mouth disease were used as parameters to assess the efficacy of emergency vaccination. The clinical protection was estimated based on the appearance...... publication bias tests. In total, 31 studies were included in the analyses, of which 26 were peer-reviewed studies, 1 was a symposium study and 4 were unpublished studies. Cattle, swine and sheep were well protected against clinical disease and foot and mouth disease infection following the use of emergency...... vaccine. Fortunately, no significant bias that would alter the conclusions was encountered in the analysis. Meta-analysis can be a useful tool to summarize literature results from a systematic review of the efficacy of foot and mouth disease emergency vaccination....

  18. Vaccination efficacy and environmental pollution

    DEFF Research Database (Denmark)

    Kielsen, Katrine; Shamim, Z; Ryder, L. P.

    2016-01-01

    This chapter focuses on the limited number of environmental pollutants for which such vaccination data exists, including polychlorinated biphenyls (PCBs) and perfluorinated alkylate substances (PFAS), which are described individually. In general, elevated exposures to these compounds were...... in a more direct manner. The presented results in this chapter might explain some of the wide variation in antibody responses to immunization and support the hypothesis that some people today could be immunocompromised because of their exposure to environmental pollutants. Due to their high persistence...

  19. Efficacy of combined vaccination against Mycoplasma hyopneumoniae and porcine reproductive and respiratory syndrome virus in dually infected pigs.

    Science.gov (United States)

    Bourry, Olivier; Fablet, Christelle; Simon, Gaëlle; Marois-Créhan, Corinne

    2015-11-18

    Porcine respiratory disease complex (PRDC) is one of the main causes of economic losses for swine producers. This complex is due to a combination of different pathogens and their interactions. Two major pathogens involved in PRDC are Mycoplasma hyopneumoniae (Mhp) and porcine reproductive and respiratory syndrome virus (PRRSV). The objectives of this study were (i) to develop an experimental model of dual Mhp/PRRSV infection in SPF pigs with European strains of Mhp and PRRSV and (ii) to assess and compare the effects of single Mhp, single PRRSV or combined Mhp/PRRSV vaccination against this dual infection. Pigs dually infected with Mhp and PRRSV showed a combination of symptoms characteristic of each pathogen but no significant exacerbation of pathogenicity. Thus, the co-infected pigs displayed coughing and pneumonia typical of Mhp infection in addition to PRRSV-related hyperthermia and decrease in average daily gain (ADG). Hyperthermia was reduced in PRRSV vaccinated animals (single or combined vaccination), whereas ADG was restored in Mhp/PRRSV vaccinated pigs only. Regarding respiratory symptoms and lung lesions, no vaccine decreased coughing. However, all vaccines reduced the pneumonia score but more so in animals receiving the Mhp vaccine, whether single or combined. This vaccine also decreased the Mhp load in the respiratory tract. In conclusion, combined vaccination against both Mhp and PRRSV efficiently pooled the efficacy of each single PRRSV and Mhp vaccination and could be an interesting tool to control PRDC in European swine production. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. The swine flu vaccine, public attitudes, and researcher interpretations: a systematic review of qualitative research.

    Science.gov (United States)

    Carlsen, Benedicte; Glenton, Claire

    2016-06-24

    During pandemics, health authorities may be uncertain about the spread and severity of the disease and the effectiveness and safety of available interventions. This was the case during the swine flu (H1N1) pandemic of 2009-2010, and governments were forced to make decisions despite these uncertainties. While many countries chose to implement wide scale vaccination programmes, few accomplished their vaccination goals. Many research studies aiming to explore barriers and facilitators to vaccine uptake have been conducted in the aftermath of the pandemic, including several qualitative studies. 1. To explore public attitudes to the swine flu vaccine in different countries through a review of qualitative primary studies. 2. To describe and discuss the implications drawn by the primary study authors. Systematic review of qualitative research studies, using a broadly comparative cross case-study approach. Study quality was appraised using an adaptation of the Critical Appraisal Skills Programme (CASP) quality assessment tool. The review indicates that the public had varying opinions about disease risk and prevalence and had concerns about vaccine safety. Most primary study authors concluded that participants were uninformed, and that more information about the disease and the vaccine would have led to an increase in vaccine uptake. We find these conclusions problematic. We suggest instead that people's questions and concerns were legitimate given the uncertainties of the situation at the time and the fact that the authorities did not have the necessary information to convince the public. Our quality assessment of the included studies points to a lack of reflexivity and a lack of information about study context. We suggest that these study weaknesses are tied to primary study authors' lack of acknowledgement of the uncertainties surrounding the disease and the vaccine. While primary study authors suggest that authorities could increase vaccine uptake through increased

  1. Toward the development of a one-dose classical swine fever subunit vaccine: antigen titration, immunity onset, and duration of immunity

    Science.gov (United States)

    Madera, Rachel F.; Wang, Lihua; Gong, Wenjie; Burakova, Yulia; Buist, Sterling; Nietfeld, Jerome; Henningson, Jamie; Cino-Ozuna, Ada G.; Tu, Changchun

    2018-01-01

    Highly contagious classical swine fever (CSF) remains a major trade and health problem in the pig industry, resulting in large economic losses worldwide. In CSF-endemic countries, attenuated CSF virus (CSFV) vaccines have been routinely used to control the disease. However, eradication of CSFV in a geographical area would require permanent reduction to zero presence of the virus. It is therefore of paramount importance to develop a safe, potent, and non-infectious CSF vaccine. We have previously reported on a cost-effective CSF E2 subunit vaccine, KNB-E2, which can protect against CSF symptoms in a single dose containing 75 µg of recombinant CSFV glycoprotein E2. In this study, we report on a series of animal studies undertaken to elucidate further the efficacy of KNB-E2. We found that pigs vaccinated with a single KNB-E2 dose containing 25 µg of recombinant CSFV glycoprotein E2 were protected from clinical symptoms of CSF. In addition, KNB-E2-mediated reduction of CSF symptoms was observed at two weeks post-vaccination and the vaccinated pigs continued to exhibit reduced CSF clinical signs when virus challenged at two months and four months post-vaccination. These results suggest that KNB-E2 effectively reduces CSF clinical signs, indicating the potential of this vaccine for safely minimizing CSF-related losses. PMID:29510474

  2. The role of attitudes about vaccine safety, efficacy, and value in explaining parents' reported vaccination behavior.

    Science.gov (United States)

    Lavail, Katherine Hart; Kennedy, Allison Michelle

    2013-10-01

    To explain vaccine confidence as it related to parents' decisions to vaccinate their children with recommended vaccines, and to develop a confidence measure to efficiently and effectively predict parents' self-reported vaccine behaviors. A sample of parents with at least one child younger than 6 years (n = 376) was analyzed using data from the HealthStyles 2010 survey. Questions were grouped into block variables to create three confidence constructs: value, safety, and efficacy. Regression equations controlling for demographic characteristics were used to identify the confidence construct(s) that best predicted parents' self-reported vaccination decisions (accept all, some, or none of the recommended childhood vaccines). Among the three constructs evaluated, confidence in the value of vaccines, that is the belief that vaccines are important and vaccinating one's children is the right thing to do, was the best predictor of parents' vaccine decisions, F(2, 351) = 119.199, p parents' self-reported vaccine decisions. Confidence in the safety or efficacy of vaccines failed to account for additional significant variance in parent-reported vaccination behavior. Confidence in the value of vaccines is a helpful predictor of parent-reported vaccination behavior. Attitudinal constructs of confidence in the safety and efficacy of vaccines failed to account for additional significant variance in parents' vaccination behaviors. Future research should assess the role of vaccine knowledge and tangible barriers, such as access and cost, to further explain parents' vaccination behaviors.

  3. Preventive vaccination contributes to control classical swine fever in wild boar (Sus scrofa sp.).

    Science.gov (United States)

    Rossi, S; Pol, F; Forot, B; Masse-Provin, N; Rigaux, S; Bronner, A; Le Potier, M-F

    2010-04-21

    Over the last 20 years, oral vaccination implementing a live attenuated vaccine has been experimented in Europe in order to control classical swine fever (CSF) in Wild Boar (Sus scrofa sp.). This has generally led to an enhanced seroprevalence and a decreased viroprevalence at the scale of the whole vaccinated populations, but no quantitative analysis has demonstrated the protective effect of preventive vaccination or intensive baiting. In the present paper we conducted a retrospective analysis at the scale of the municipality, taking into account the local dynamics and possible covariates of infection to test the effect of preventive vaccination and of the baiting effort. To be efficient, vaccination was expected to increase seroprevalence above the level considered as suitable for preventing disease invasion (40-60%) independently of infection, to protect free areas from disease invasion or contribute to control subsequent disease intensity and duration. We also hypothesized that a better baiting effort would be correlated with an improvement of immunisation and disease control. In uninfected municipalities, seroprevalence increased up to 40% after 1 year, i.e., three vaccination campaigns. We observed a significant protective effect of preventive vaccination, especially within municipalities that had been vaccinated at least 1 year before disease emergence and where virus detection did not last more than one quarter. On the other hand, we did not detect a significant effect of the baiting effort on local seroprevalence or disease dynamics, suggesting that the baiting system could be improved. We discuss these results regarding the improvement of management measures and further research perspective. Copyright 2009 Elsevier B.V. All rights reserved.

  4. Early protection events in swine immunized with an experimental live attenuated classical swine fever marker vaccine, FlagT4G.

    Directory of Open Access Journals (Sweden)

    Lauren G Holinka

    Full Text Available Prophylactic vaccination using live attenuated classical swine fever (CSF vaccines has been a very effective method to control the disease in endemic regions and during outbreaks in previously disease-free areas. These vaccines confer effective protection against the disease at early times post-vaccination although the mechanisms mediating the protection are poorly characterized. Here we present the events occurring after the administration of our in-house developed live attenuated marker vaccine, FlagT4Gv. We previously reported that FlagT4Gv intramuscular (IM administered conferred effective protection against intranasal challenge with virulent CSFV (BICv as early as 7 days post-vaccination. Here we report that FlagT4Gv is able to induce protection against disease as early as three days post-vaccination. Immunohistochemical testing of tissues from FlagT4Gv-inoculated animals showed that tonsils were colonized by the vaccine virus by day 3 post-inoculation. There was a complete absence of BICv in tonsils of FlagT4Gv-inoculated animals which had been intranasal (IN challenged with BICv 3 days after FlagT4Gv infection, confirming that FlagT4Gv inoculation confers sterile immunity. Analysis of systemic levels of 19 different cytokines in vaccinated animals demonstrated an increase of IFN-α three days after FlagT4Gv inoculation compared with mock infected controls.

  5. Efficacy of tiamulin as a growth promotant for growing swine.

    Science.gov (United States)

    Cromwell, G L; Stahly, T S

    1985-01-01

    A study involving 244 pigs initially averaging 13 kg was conducted at two stations to evaluate tiamulin as a growth promotant for growing swine. In each experiment, four replicate pens of five (Exp. 1) or six (Exp. 2) pigs/pen were used to evaluate each treatment. In Exp. 1, pigs were fed 0, 11, 22 or 44 ppm tiamulin from 15 to 58 kg, then fed a nonmedicated control diet for the remainder of the experiment (to 95 kg). In Exp. 2, pigs were fed 0, 2.75, 5.5, 11 or 22 ppm tiamulin from 11 to 56 kg, followed by the nonmedicated control diet (to 95 kg). In each experiment, carbadox (55 ppm) was included as a positive control and was fed to an average weight of 35 kg, followed by the control diet. Averaged across all dietary levels, tiamulin resulted in a 14.1% improvement in gain and a 5.7% improvement in feed:gain ratio during the first 28 to 35 d of the experiment (to 30 kg). These improvements were slightly less than those resulting from the feeding of carbadox during the same period (21.5 and 6.9%, respectively). From 13 to 57 kg, pigs fed tiamulin gained 11.6% faster and 3.1% more efficiently than did controls. Over the entire experiment (13 to 95 kg), tiamulin-fed pigs gained 5.7% faster than did controls, even though the tiamulin was withdrawn at 57 kg body weight. Growth rate from 13 to 57 kg plateaued at the 11-ppm dietary level of tiamulin; whereas, feed:gain ratio plateaued at the 22-ppm level. The results indicate that tiamulin is an effective growth promotant for growing swine.

  6. Sieve analysis in HIV-1 vaccine efficacy trials.

    Science.gov (United States)

    Edlefsen, Paul T; Gilbert, Peter B; Rolland, Morgane

    2013-09-01

    The genetic characterization of HIV-1 breakthrough infections in vaccine and placebo recipients offers new ways to assess vaccine efficacy trials. Statistical and sequence analysis methods provide opportunities to mine the mechanisms behind the effect of an HIV vaccine. The release of results from two HIV-1 vaccine efficacy trials, Step/HVTN-502 (HIV Vaccine Trials Network-502) and RV144, led to numerous studies in the last 5 years, including efforts to sequence HIV-1 breakthrough infections and compare viral characteristics between the vaccine and placebo groups. Novel genetic and statistical analysis methods uncovered features that distinguished founder viruses isolated from vaccinees from those isolated from placebo recipients, and identified HIV-1 genetic targets of vaccine-induced immune responses. Studies of HIV-1 breakthrough infections in vaccine efficacy trials can provide an independent confirmation to correlates of risk studies, as they take advantage of vaccine/placebo comparisons, whereas correlates of risk analyses are limited to vaccine recipients. Through the identification of viral determinants impacted by vaccine-mediated host immune responses, sieve analyses can shed light on potential mechanisms of vaccine protection.

  7. Immunogenicity, protective efficacy and mechanism of novel CCS adjuvanted influenza vaccine.

    Science.gov (United States)

    Even-Or, Orli; Samira, Sarit; Rochlin, Eli; Balasingam, Shobana; Mann, Alex J; Lambkin-Williams, Rob; Spira, Jack; Goldwaser, Itzhak; Ellis, Ronald; Barenholz, Yechezkel

    2010-09-07

    We optimized the immunogenicity of adjuvanted seasonal influenza vaccine based on commercial split influenza virus as an antigen (hemagglutinin = HA) and on a novel polycationic liposome as a potent adjuvant and efficient antigen carrier (CCS/C-HA vaccine). The vaccine was characterized physicochemically, and the mechanism of action of CCS/C as antigen carrier and adjuvant was studied. The optimized CCS/C-HA split virus vaccine, when administered intramuscularly (i.m.), is significantly more immunogenic in mice, rats and ferrets than split virus HA vaccine alone, and it provides for protective immunity in ferrets and mice against live virus challenge that exceeds the degree of efficacy of the split virus vaccine. Similar adjuvant effects of optimized CCS/C are also observed in mice for H1N1 swine influenza antigen. The CCS/C-HA vaccine enhances immune responses via the Th1 and Th2 pathways, and it increases both the humoral responses and the production of IL-2 and IFN-γ but not of the pro-inflammatory factor TNFα. In mice, levels of CD4(+) and CD8(+) T-cells and of MHC II and CD40 co-stimulatory molecules are also elevated. Structure-function relationship studies of the CCS molecule as an adjuvant/carrier show that replacing the saturated palmitoyl acyl chain with the mono-unsaturated oleoyl (C18:1) chain affects neither size distribution and zeta potential nor immune responses in mice. However, replacing the polyalkylamine head group spermine (having two secondary amines) with spermidine (having only one secondary amine) reduces the enhancement of the immune response by ∼ 50%, while polyalkylamines by themselves are ineffective in improving the immunogenicity over the commercial HA vaccine. This highlights the importance of the particulate nature of the carrier and the polyalkylamine secondary amines in the enhancement of the immune responses against seasonal influenza. Altogether, our results suggest that the CCS/C polycationic liposomes combine the

  8. Measles incidence, vaccine efficacy, and mortality in two urban African areas with high vaccination coverage

    DEFF Research Database (Denmark)

    Aaby, Peter; Knudsen, K; Jensen, T G

    1990-01-01

    Measles incidence, vaccine efficacy, and mortality were examined prospectively in two districts in Bissau where vaccine coverage for children aged 12-23 months was 81% (Bandim 1) and 61% (Bandim 2). There was little difference in cumulative measles incidence before 9 months of age (6.1% and 7.......6%, respectively). Between 9 months and 2 years of age, however, 6.1% contracted measles in Bandim 1 and 13.7% in Bandim 2. Even adjusting for vaccination status, incidence was significantly higher in Bandim 2 (relative risk 1.6, P = .04). Even though 95% of the children had measles antibodies after vaccination......, vaccine efficacy was not more than 68% (95% confidence interval [CI] 39%-84%) and was unrelated to age at vaccination. Unvaccinated children had a mortality hazard ratio of 3.0 compared with vaccinated children (P = .002), indicating a protective efficacy against death of 66% (CI 32%-83%) of measles...

  9. Efficacy of antibiotic treatment and test-based culling strategies for eradicating brucellosis in commercial swine herds

    NARCIS (Netherlands)

    Dieste-Pérez, L.; Frankena, K.; Blasco, J.M.; Muñoz, P.M.; Jong, de M.C.M.

    2016-01-01

    Swine brucellosis caused by Brucella suis biovar 2 is an emerging disease in continental Europe. Without effective vaccines being available, the European Food Safety Authority (EFSA) recommends the full depopulation of infected herds as the only strategy to eradicate B. suis outbreaks. Using data

  10. Efficacy of antibiotic treatment and test-based culling strategies for eradicating brucellosis in commercial swine herds

    NARCIS (Netherlands)

    Dieste-Pérez, L.; Frankena, K.; Blasco, J. M.; Muñoz, P. M.; De Jong, M. C M

    2016-01-01

    Swine brucellosis caused by Brucella suis biovar 2 is an emerging disease in continental Europe. Without effective vaccines being available, the European Food Safety Authority (EFSA) recommends the full depopulation of infected herds as the only strategy to eradicate B. suis outbreaks. Using data

  11. Reassortant H1N1 influenza virus vaccines protect pigs against pandemic H1N1 influenza virus and H1N2 swine influenza virus challenge.

    Science.gov (United States)

    Yang, Huanliang; Chen, Yan; Shi, Jianzhong; Guo, Jing; Xin, Xiaoguang; Zhang, Jian; Wang, Dayan; Shu, Yuelong; Qiao, Chuanling; Chen, Hualan

    2011-09-28

    Influenza A (H1N1) virus has caused human influenza outbreaks in a worldwide pandemic since April 2009. Pigs have been found to be susceptible to this influenza virus under experimental and natural conditions, raising concern about their potential role in the pandemic spread of the virus. In this study, we generated a high-growth reassortant virus (SC/PR8) that contains the hemagglutinin (HA) and neuraminidase (NA) genes from a novel H1N1 isolate, A/Sichuan/1/2009 (SC/09), and six internal genes from A/Puerto Rico/8/34 (PR8) virus, by genetic reassortment. The immunogenicity and protective efficacy of this reassortant virus were evaluated at different doses in a challenge model using a homologous SC/09 or heterologous A/Swine/Guangdong/1/06(H1N2) virus (GD/06). Two doses of SC/PR8 virus vaccine elicited high-titer serum hemagglutination inhibiting (HI) antibodies specific for the 2009 H1N1 virus and conferred complete protection against challenge with either SC/09 or GD/06 virus, with reduced lung lesions and viral shedding in vaccine-inoculated animals compared with non-vaccinated control animals. These results indicated for the first time that a high-growth SC/PR8 reassortant H1N1 virus exhibits properties that are desirable to be a promising vaccine candidate for use in swine in the event of a pandemic H1N1 influenza. Copyright © 2011 Elsevier B.V. All rights reserved.

  12. Heterogeneity of Rotavirus Vaccine Efficacy Among Infants in Developing Countries.

    Science.gov (United States)

    Gruber, Joann F; Hille, Darcy A; Liu, G Frank; Kaplan, Susan S; Nelson, Micki; Goveia, Michelle G; Mast, T Christopher

    2017-01-01

    Rotavirus is the leading cause of severe diarrhea worldwide in young children. Although rotavirus vaccine efficacy is high in developed countries, efficacy is lower in developing countries. Here, we investigated heterogeneity of rotavirus vaccine efficacy by infant characteristics in developing countries. An exploratory, post hoc analysis was conducted using randomized controlled trial data of the pentavalent rotavirus vaccine (RV5) conducted in Africa and Asia (NCT00362648). Infants received either 3 doses of vaccine/placebo and were followed for up to 2 years. Within subgroups, vaccine efficacies and 95% confidence intervals (CIs) against rotavirus gastroenteritis (RVGE) were estimated using Poisson regression. We assessed heterogeneity of efficacy by age at first dose, gender, breastfeeding status and nutrition status. African children receiving the first dose at efficacy (23.7%; 95% CI: -8.2%-46.3%) than those vaccinated at ≥8 weeks (59.1%; 95% CI: 34.0%-74.6%). Marginally statistically significant differences were observed by age at first dose, gender and underweight status in Ghana and gender in Asian countries. Heterogeneity of efficacy was observed for age at first dose in African countries. This was an exploratory analysis; additional studies are needed to validate these results.

  13. Impact of information on intentions to vaccinate in a potential epidemic: Swine-origin Influenza A (H1N1).

    Science.gov (United States)

    Chanel, Olivier; Luchini, Stéphane; Massoni, Sébastien; Vergnaud, Jean-Christophe

    2011-01-01

    Vaccination campaigns to prevent the spread of epidemics are successful only if the targeted populations subscribe to the recommendations of health authorities. However, because compulsory vaccination is hardly conceivable in modern democracies, governments need to convince their populations through efficient and persuasive information campaigns. In the context of the swine-origin A (H1N1) 2009 pandemic, we use an interactive study among the general public in the South of France, with 175 participants, to explore what type of information can induce change in vaccination intentions at both aggregate and individual levels. We find that individual attitudes to vaccination are based on rational appraisal of the situation, and that it is information of a purely scientific nature that has the only significant positive effect on intention to vaccinate. Copyright © 2010 Elsevier Ltd. All rights reserved.

  14. Acellular pertussis vaccines--a question of efficacy.

    Science.gov (United States)

    Olin, P

    1995-06-01

    Whole cell pertussis vaccine is considered to offer at least 80% protection against typical whooping cough. The quest for an equally effective but less reactogenic vaccine is now drawing to a close. During the forthcoming year a number of efficacy trials of acellular pertussis vaccines will be terminated. A variety of vaccines containing one, two, three or five purified pertussis antigens are being tested in Germany, Italy, Senegal and Sweden. About 30,000 infants have been enrolled in placebo-controlled studies and more than 100,000 in whole cell vaccine-controlled trials. The final plans for analysis of a Swedish placebo-controlled trial of whole cell and acellular vaccines is presented. Due to the unexpected high incidence of pertussis in Sweden during 1993-1994, relative risk comparisons between vaccines will be attempted in that trial, in addition to estimating absolute efficacy. A crucial issue is to what extent data may be compared between trials, given differences in design, vaccination schedules, and chosen endpoints. A primary case definition of laboratory-confirmed pertussis with at least 21 days of paroxysmal cough have been adopted in most trials. Pre-planned meta-analysis using this single endpoint will facilitate comparisons between vaccines. Serological correlates to protection in individuals will be sought in the ongoing placebo-controlled trials. The concept of a serological correlate valid for a vaccinated population but not necessarily for the vaccinated individual, as is the case with Hib vaccines, may turn out to be the only alternative to performing large efficacy trials in the future.

  15. Immunogenicity and Clinical Efficacy of Influenza Vaccination In Pregnancy

    Directory of Open Access Journals (Sweden)

    Alexander W Kay

    2015-06-01

    Full Text Available Pregnant women are at high risk from influenza due to disproportionate morbidity, mortality, and adverse pregnancy outcomes following infection. As such, they are classified as a high priority group for vaccination. However, changes in the maternal immune system required to accommodate the allogeneic fetus may alter the immunogenicity of influenza vaccines. A large number of studies have evaluated the safety of the influenza vaccine. Here, we will review available studies on the immunogenicity and efficacy of the influenza vaccine during pregnancy, focusing on both humoral and cellular immunity.

  16. Evaluation of classical swine fever virus antibody detection assays with an emphasis on the differentiation of infected from vaccinated animals

    DEFF Research Database (Denmark)

    Schroeder, S.; von Rosen, Tanya; Blome, S.

    2012-01-01

    vaccinated animals (DIVA). The Chekit* CSF-Sero and the HerdChek* CSFV Ab, both of which detect antibodies against the E2 protein of classical swine fever virus (CSFV), had the highest sensitivity. Both tests were practicable and showed good reproducibility. Comparable sensitivity was shown by the Chekit......The aim of this study was to evaluate the general characteristics of commercially available enzyme-linked immunosorbent assays (ELISAs) to detect antibody against classical swine fever (CSF), as well as to assess their potential use as accompanying marker tests able to differentiate infected from......* CSF-Marker, an Erns ELISA. However, this test does not allow differentiation between antibodies directed against ruminant pestiviruses and those against CSFV. Therefore, it is not suitable for use with the chimeric marker vaccines tested. The PrioCHECK® CSFV Erns was the only ELISA suitable for use...

  17. Protection of human influenza vaccines against a reassortant swine influenza virus of pandemic H1N1 origin using a pig model.

    Science.gov (United States)

    Arunorat, Jirapat; Charoenvisal, Nataya; Woonwong, Yonlayong; Kedkovid, Roongtham; Jittimanee, Supattra; Sitthicharoenchai, Panchan; Kesdangsakonwut, Sawang; Poolperm, Pariwat; Thanawongnuwech, Roongroje

    2017-10-01

    Since the pandemic H1N1 emergence in 2009 (pdmH1N1), many reassortant pdmH1N1 viruses emerged and found circulating in the pig population worldwide. Currently, commercial human subunit vaccines are used commonly to prevent the influenza symptom based on the WHO recommendation. In case of current reassortant swine influenza viruses transmitting from pigs to humans, the efficacy of current human influenza vaccines is of interest. In this study, influenza A negative pigs were vaccinated with selected commercial human subunit vaccines and challenged with rH3N2. All sera were tested with both HI and SN assays using four representative viruses from the surveillance data in 2012 (enH1N1, pdmH1N1, rH1N2 and rH3N2). The results showed no significant differences in clinical signs and macroscopic and microscopic findings among groups. However, all pig sera from vaccinated groups had protective HI titers to the enH1N1, pdmH1N1 and rH1N2 at 21DPV onward and had protective SN titers only to pdmH1N1and rH1N2 at 21DPV onward. SN test results appeared more specific than those of HI tests. All tested sera had no cross-reactivity against the rH3N2. Both studied human subunit vaccines failed to protect and to stop viral shedding with no evidence of serological reaction against rH3N2. SIV surveillance is essential for monitoring a novel SIV emergence potentially for zoonosis. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. EFFICACY AND SAFETY OF THE INFLUENZA VACCINE AMONG CHILDREN WITH DIFFERENT HEALTH CONDITIONS

    OpenAIRE

    M.G. Galitskaya

    2007-01-01

    Efficacy and safety of vaccine «Grippol» among children with different health status was analyzed. The most efficacy of the influenza vaccine revealed in the group of children with compromised health status, as well as in the group of allergic children. The safety of influenza vaccination was confirmed in children with different health conditions.Key words: children, vaccination, influenza, efficacy, safety.

  19. Simultaneous deletion of the 9GL and UK genes from the African swine fever virus Georgia 2007 isolate results in virus attenuation and may be a potential virus vaccine strain

    Science.gov (United States)

    African Swine Fever Virus (ASFV) is the etiological agent of a contagious and often lethal viral disease of domestic pigs that has significant economic consequences for the swine industry. The control of African Swine Fever (ASF) has been hampered by the unavailability of vaccines. Successful experi...

  20. Comparison of two real-time RT-PCR assays for differentiation of C-strain vaccinated from classical swine fever infected pigs and wild boars

    DEFF Research Database (Denmark)

    Widén, F.; Everett, H.; Blome, S.

    2014-01-01

    Classical swine fever is one of the most important infectious diseases for the pig industry worldwide due to its economic impact. Vaccination is an effective means to control disease, however within the EU its regular use is banned owing to the inability to differentiate infected and vaccinated a...

  1. Immunogenicity of Recombinant Classic Swine Fever Virus CD8+ T Lymphocyte Epitope and Porcine Parvovirus VP2 Antigen Coexpressed by Lactobacillus casei in Swine via Oral Vaccination

    Science.gov (United States)

    Xu, Yigang; Cui, Lichun; Tian, Changyong; Zhang, Guocai; Huo, Guicheng; Tang, Lijie; Li, Yijing

    2011-01-01

    Classical swine fever virus (CSFV) and porcine parvovirus (PPV) are highly contagious pathogens, resulting in enormous economic losses in pig industries worldwide. Because vaccines play an important role in disease control, researchers are seeking improved vaccines that could induce antiviral immune responses against CSFV and PPV at the mucosal and systemic levels simultaneously. In this study, a genetically engineered Lactobacillus strain coexpressing the CSFV-specific cytotoxic T lymphocyte (CTL) epitope 290 and the VP2 antigen of PPV was developed, and its immunopotentiating capacity as an oral vaccine in pigs was analyzed. The data demonstrated that in the absence of any adjuvant, the recombinant Lactobacillus strain can efficiently stimulate mucosal and systemic CSFV-specific CD8+ CTL responses to protect pigs against CSFV challenge. Moreover, anti-PPV-VP2 serum IgG and mucosal IgA were induced in pigs immunized orally with the recombinant Lactobacillus strain, showing a neutralizing effect on PPV infection. The results suggest that the recombinant Lactobacillus microecological agent may be a valuable component of a strategy for development of a vaccine against CSFV and PPV. PMID:21940406

  2. Mucosal Immunity and Protective Efficacy of Intranasal Inactivated Influenza Vaccine Is Improved by Chitosan Nanoparticle Delivery in Pigs

    Directory of Open Access Journals (Sweden)

    Santosh Dhakal

    2018-05-01

    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

  3. Efficacy of the oral pentavalent rotavirus vaccine in Mali.

    Science.gov (United States)

    Sow, Samba O; Tapia, Milagritos; Haidara, Fadima C; Ciarlet, Max; Diallo, Fatoumata; Kodio, Mamoudou; Doumbia, Moussa; Dembélé, Rokiatou D; Traoré, Oumou; Onwuchekwa, Uma U; Lewis, Kristen D C; Victor, John C; Steele, A Duncan; Neuzil, Kathleen M; Kotloff, Karen L; Levine, Myron M

    2012-04-27

    The oral, pentavalent rotavirus vaccine (PRV), RotaTeq was assessed for prevention of severe rotavirus gastroenteritis (RVGE) in young children in two multi-site, randomized, placebo-controlled field trials; one in Asia (Vietnam and Bangladesh) and the other in sub-Saharan Africa (Ghana, Kenya and Mali). The efficacy results for the Mali site of the multi-country trial are presented here. We randomly assigned infants in a 1:1 ratio to receive 3 doses of PRV/placebo at approximately 6, 10, and 14 weeks of age. Gastroenteritis episodes were captured passively at the local health centers and by home visits. The primary study outcome was severe RVGE, as defined by a score of ≥ 11 using the Vesikari Clinical Scoring System occurring ≥ 14 days after the third dose until the end of the study. Other efficacy analyses included efficacy against severe RVGE through the first year and during the second years of life, as well as efficacy after receiving at least one dose of vaccine. In total, 1960 infants were enrolled in the trial at the Mali site and sera were collected on a subset of infants (approximately 150) for immunogenicity testing. In the first year of follow-up, largely due to cultural practices to visit traditional healers as the first point of care, the point estimate of efficacy was unreliable: the per protocol vaccine efficacy against severe RVGE was 1% (95% confidence interval [CI]: -431.7, 81.6); the intention-to-treat vaccine efficacy was 42.9% (95% CI: -125.7, 87.7). During the second year of follow-up, after the surveillance system was modified to adapt to local customs and health care seeking practices, the point estimate of per-protocol vaccine efficacy was 19.2% (95% CI: -23.1,47.3%). 82.5% of Malian infants (95% CI: 70.1,91.3%) who received PRV mounted a seroresponse (≥ 3-fold rise from baseline (prevaccination) to post-dose 3 vaccination) of anti-rotavirus immunoglobulin A antibody, with a post third-dose geometric mean titer (GMT) of 31.3 units

  4. Mucosal Immunity and Protective Efficacy of Intranasal Inactivated Influenza Vaccine Is Improved by Chitosan Nanoparticle Delivery in Pigs.

    Science.gov (United States)

    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

    2018-01-01

    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

  5. Meta-analysis of variables affecting mouse protection efficacy of whole organism Brucella vaccines and vaccine candidates

    Science.gov (United States)

    2013-01-01

    Background Vaccine protection investigation includes three processes: vaccination, pathogen challenge, and vaccine protection efficacy assessment. Many variables can affect the results of vaccine protection. Brucella, a genus of facultative intracellular bacteria, is the etiologic agent of brucellosis in humans and multiple animal species. Extensive research has been conducted in developing effective live attenuated Brucella vaccines. We hypothesized that some variables play a more important role than others in determining vaccine protective efficacy. Using Brucella vaccines and vaccine candidates as study models, this hypothesis was tested by meta-analysis of Brucella vaccine studies reported in the literature. Results Nineteen variables related to vaccine-induced protection of mice against infection with virulent brucellae were selected based on modeling investigation of the vaccine protection processes. The variable "vaccine protection efficacy" was set as a dependent variable while the other eighteen were set as independent variables. Discrete or continuous values were collected from papers for each variable of each data set. In total, 401 experimental groups were manually annotated from 74 peer-reviewed publications containing mouse protection data for live attenuated Brucella vaccines or vaccine candidates. Our ANOVA analysis indicated that nine variables contributed significantly (P-value Brucella vaccine protection efficacy: vaccine strain, vaccination host (mouse) strain, vaccination dose, vaccination route, challenge pathogen strain, challenge route, challenge-killing interval, colony forming units (CFUs) in mouse spleen, and CFU reduction compared to control group. The other 10 variables (e.g., mouse age, vaccination-challenge interval, and challenge dose) were not found to be statistically significant (P-value > 0.05). The protection level of RB51 was sacrificed when the values of several variables (e.g., vaccination route, vaccine viability, and

  6. Comparative efficacy of Rubini, Jeryl-Lynn and Urabe mumps vaccine in an Asian population.

    Science.gov (United States)

    Ong, Gary; Goh, Kee Tai; Ma, Stefan; Chew, Suok Kai

    2005-11-01

    The comparative efficacy of the three mumps vaccine strains (Jeryl-Lynn, Urabe and Rubini) was conducted in an Asian population from data arising from an epidemiological investigation of seven institutional outbreaks of mumps in Singapore. Demographic information (gender, age, ethnic group), clinical presentation and vaccination history (date and place of mumps vaccination, type of mumps vaccine received) of all children who attended the six childcare centres and one primary school where outbreaks of 20 or more cases of mumps occurred in 1999 were collected. The attack rate of the unvaccinated group and the attack rates of the vaccine groups (for each vaccine strain) were determined and the vaccine efficacy of the three vaccines calculated. The vaccine efficacy of the Jeryl-Lynn strain, Urabe strain and Rubini strain mumps vaccine were 80.7, 54.4 and -55.3%, respectively. Rubini strain mumps vaccine conferred no protection and has since been deregistered in Singapore.

  7. Vaccination-challenge studies with a Port Chalmers/73 (H3N2)-based swine influenza virus vaccine: Reflections on vaccine strain updates and on the vaccine potency test.

    Science.gov (United States)

    De Vleeschauwer, Annebel; Qiu, Yu; Van Reeth, Kristien

    2015-05-11

    The human A/Port Chalmers/1/73 (H3N2) influenza virus strain, the supposed ancestor of European H3N2 swine influenza viruses (SIVs), was used in most commercial SIV vaccines in Europe until recently. If manufacturers want to update vaccine strains, they have to perform laborious intratracheal (IT) challenge experiments and demonstrate reduced virus titres in the lungs of vaccinated pigs. We aimed to examine (a) the ability of a Port Chalmers/73-based commercial vaccine to induce cross-protection against a contemporary European H3N2 SIV and serologic cross-reaction against H3N2 SIVs from Europe and North America and (b) the validity of intranasal (IN) challenge and virus titrations of nasal swabs as alternatives for IT challenge and titrations of lung tissue in vaccine potency tests. Pigs were vaccinated with Suvaxyn Flu(®) and challenged by the IT or IN route with sw/Gent/172/08. Post-vaccination sera were examined in haemagglutination-inhibition assays against vaccine and challenge strains and additional H3N2 SIVs from Europe and North America, including an H3N2 variant virus. Tissues of the respiratory tract and nasal swabs were collected 3 days post challenge (DPCh) and from 0-7 DPCh, respectively, and examined by virus titration. Two vaccinations consistently induced cross-reactive antibodies against European H3N2 SIVs from 1998-2012, but minimal or undetectable antibody titres against North American viruses. Challenge virus titres in the lungs, trachea and nasal mucosa of the vaccinated pigs were significantly reduced after both IT and IN challenge. Yet the reduction of virus titres and nasal shedding was greater after IT challenge. The Port Chalmers/73-based vaccine still offered protection against a European H3N2 SIV isolated 35 years later and with only 86.9% amino acid homology in its HA1, but it is unlikely to protect against H3N2 SIVs that are endemic in North America. We use our data to reflect on vaccine strain updates and on the vaccine potency test

  8. Obtaining classical swine fever virus E2 recombinant protein and DNA-vaccine on the basis of one subunit

    International Nuclear Information System (INIS)

    Deryabin, O.; Deryabina, O.; Verbitskiy, P.; Kordyum, V.

    2005-01-01

    Three forms of E2 recombinant protein were expressed in E. coli. Swine sera obtained against different forms of the recombinant protein were cross-studied with indirect ELISA. Using individual proteins as an antigen, only 15% of sera against other forms of protein reacted positively, while 100% of heterologous sera showed positive reaction with fused protein. Challenge experiments showed the existence of protective action only from the individual protein. Specificity and activity of sera obtained from the animals after control challenge was confirmed in a blocking variant of ELISA. Genetic construction used a eukaryotic vector that contained the E2 protein gene. Immunization of mice with the resulting DNA induced synthesis of specific antibodies, the titre of which increased considerably after additional single immunization with the E2 recombinant protein, expressed in E. coli. This demonstrated the effectiveness of animal priming by DNA vaccine, and the possibility of using the E2 recombinant protein in E. coli for booster vaccination. (author)

  9. Understanding reduced rotavirus vaccine efficacy in low socio-economic settings.

    Directory of Open Access Journals (Sweden)

    Benjamin A Lopman

    Full Text Available Rotavirus vaccine efficacy ranges from >90% in high socio-economic settings (SES to 50% in low SES. With the imminent introduction of rotavirus vaccine in low SES countries, understanding reasons for reduced efficacy in these settings could identify strategies to improve vaccine performance.We developed a mathematical model to predict rotavirus vaccine efficacy in high, middle and low SES based on data specific for each setting on incidence, protection conferred by natural infection and immune response to vaccination. We then examined factors affecting efficacy.Vaccination was predicted to prevent 93%, 86% and 51% of severe rotavirus gastroenteritis in high, middle and low SES, respectively. Also predicted was that vaccines are most effective against severe disease and efficacy declines with age in low but not high SES. Reduced immunogenicity of vaccination and reduced protection conferred by natural infection are the main factors that compromise efficacy in low SES.The continued risk of severe disease in non-primary natural infections in low SES is a key factor underpinning reduced efficacy of rotavirus vaccines. Predicted efficacy was remarkably consistent with observed clinical trial results from different SES, validating the model. The phenomenon of reduced vaccine efficacy can be predicted by intrinsic immunological and epidemiological factors of low SES populations. Modifying aspects of the vaccine (e.g. improving immunogenicity in low SES and vaccination program (e.g. additional doses may bring improvements.

  10. Understanding reduced rotavirus vaccine efficacy in low socio-economic settings.

    Science.gov (United States)

    Lopman, Benjamin A; Pitzer, Virginia E; Sarkar, Rajiv; Gladstone, Beryl; Patel, Manish; Glasser, John; Gambhir, Manoj; Atchison, Christina; Grenfell, Bryan T; Edmunds, W John; Kang, Gagandeep; Parashar, Umesh D

    2012-01-01

    Rotavirus vaccine efficacy ranges from >90% in high socio-economic settings (SES) to 50% in low SES. With the imminent introduction of rotavirus vaccine in low SES countries, understanding reasons for reduced efficacy in these settings could identify strategies to improve vaccine performance. We developed a mathematical model to predict rotavirus vaccine efficacy in high, middle and low SES based on data specific for each setting on incidence, protection conferred by natural infection and immune response to vaccination. We then examined factors affecting efficacy. Vaccination was predicted to prevent 93%, 86% and 51% of severe rotavirus gastroenteritis in high, middle and low SES, respectively. Also predicted was that vaccines are most effective against severe disease and efficacy declines with age in low but not high SES. Reduced immunogenicity of vaccination and reduced protection conferred by natural infection are the main factors that compromise efficacy in low SES. The continued risk of severe disease in non-primary natural infections in low SES is a key factor underpinning reduced efficacy of rotavirus vaccines. Predicted efficacy was remarkably consistent with observed clinical trial results from different SES, validating the model. The phenomenon of reduced vaccine efficacy can be predicted by intrinsic immunological and epidemiological factors of low SES populations. Modifying aspects of the vaccine (e.g. improving immunogenicity in low SES) and vaccination program (e.g. additional doses) may bring improvements.

  11. Multiple linear B-cell epitopes of classical swine fever virus glycoprotein E2 expressed in E.coli as multiple epitope vaccine induces a protective immune response

    Directory of Open Access Journals (Sweden)

    Wei Jian-Chao

    2011-07-01

    Full Text Available Abstract Classical swine fever is a highly contagious disease of swine caused by classical swine fever virus, an OIE list A pathogen. Epitope-based vaccines is one of the current focuses in the development of new vaccines against classical swine fever virus (CSFV. Two B-cell linear epitopes rE2-ba from the E2 glycoprotein of CSFV, rE2-a (CFRREKPFPHRMDCVTTTVENED, aa844-865 and rE2-b (CKEDYRYAISSTNEIGLLGAGGLT, aa693-716, were constructed and heterologously expressed in Escherichia coli as multiple epitope vaccine. Fifteen 6-week-old specified-pathogen-free (SPF piglets were intramuscularly immunized with epitopes twice at 2-week intervals. All epitope-vaccinated pigs could mount an anamnestic response after booster vaccination with neutralizing antibody titers ranging from 1:16 to 1:256. At this time, the pigs were subjected to challenge infection with a dose of 1 × 106 TCID50 virulent CSFV strain. After challenge infection, all of the rE2-ba-immunized pigs were alive and without symptoms or signs of CSF. In contrast, the control pigs continuously exhibited signs of CSF and had to be euthanized because of severe clinical symptoms at 5 days post challenge infection. The data from in vivo experiments shown that the multiple epitope rE2-ba shown a greater protection (similar to that of HCLV vaccine than that of mono-epitope peptide(rE2-a or rE2-b. Therefore, The results demonstrated that this multiple epitope peptide expressed in a prokaryotic system can be used as a potential DIVA (differentiating infected from vaccinated animals vaccine. The E.coli-expressed E2 multiple B-cell linear epitopes retains correct immunogenicity and is able to induce a protective immune response against CSFV infection.

  12. Innovative Approaches to Improve Anti-Infective Vaccine Efficacy.

    Science.gov (United States)

    Yeaman, Michael R; Hennessey, John P

    2017-01-06

    Safe and efficacious vaccines are arguably the most successful medical interventions of all time. Yet the ongoing discovery of new pathogens, along with emergence of antibiotic-resistant pathogens and a burgeoning population at risk of such infections, imposes unprecedented public health challenges. To meet these challenges, innovative strategies to discover and develop new or improved anti-infective vaccines are necessary. These approaches must intersect the most meaningful insights into protective immunity and advanced technologies with capabilities to deliver immunogens for optimal immune protection. This goal is considered through several recent advances in host-pathogen relationships, conceptual strides in vaccinology, and emerging technologies. Given a clear and growing risk of pandemic disease should the threat of infection go unmet, developing vaccines that optimize protective immunity against high-priority and antibiotic-resistant pathogens represents an urgent and unifying imperative.

  13. Vaccine efficacy in senescent mice challenged with recombinant SARS-CoV bearing epidemic and zoonotic spike variants.

    Directory of Open Access Journals (Sweden)

    Damon Deming

    2006-12-01

    Full Text Available In 2003, severe acute respiratory syndrome coronavirus (SARS-CoV was identified as the etiological agent of severe acute respiratory syndrome, a disease characterized by severe pneumonia that sometimes results in death. SARS-CoV is a zoonotic virus that crossed the species barrier, most likely originating from bats or from other species including civets, raccoon dogs, domestic cats, swine, and rodents. A SARS-CoV vaccine should confer long-term protection, especially in vulnerable senescent populations, against both the 2003 epidemic strains and zoonotic strains that may yet emerge from animal reservoirs. We report the comprehensive investigation of SARS vaccine efficacy in young and senescent mice following homologous and heterologous challenge.Using Venezuelan equine encephalitis virus replicon particles (VRP expressing the 2003 epidemic Urbani SARS-CoV strain spike (S glycoprotein (VRP-S or the nucleocapsid (N protein from the same strain (VRP-N, we demonstrate that VRP-S, but not VRP-N vaccines provide complete short- and long-term protection against homologous strain challenge in young and senescent mice. To test VRP vaccine efficacy against a heterologous SARS-CoV, we used phylogenetic analyses, synthetic biology, and reverse genetics to construct a chimeric virus (icGDO3-S encoding a synthetic S glycoprotein gene of the most genetically divergent human strain, GDO3, which clusters among the zoonotic SARS-CoV. icGD03-S replicated efficiently in human airway epithelial cells and in the lungs of young and senescent mice, and was highly resistant to neutralization with antisera directed against the Urbani strain. Although VRP-S vaccines provided complete short-term protection against heterologous icGD03-S challenge in young mice, only limited protection was seen in vaccinated senescent animals. VRP-N vaccines not only failed to protect from homologous or heterologous challenge, but resulted in enhanced immunopathology with eosinophilic

  14. Safety and Efficacy of an Absorbable Filter in the Inferior Vena Cava to Prevent Pulmonary Embolism in Swine.

    Science.gov (United States)

    Huang, Steven Y; Eggers, Mitchell; McArthur, Mark J; Dixon, Katherine A; McWatters, Amanda; Dria, Stephen; Hill, Lori R; Melancon, Marites P; Steele, Joseph R; Wallace, Michael J

    2017-12-01

    Purpose To evaluate the immediate and long-term safety as well as thrombus-capturing efficacy for 5 weeks after implantation of an absorbable inferior vena cava (IVC) filter in a swine model. Materials and Methods This study was approved by the institutional animal care and use committee. Eleven absorbable IVC filters made from polydioxanone suture were deployed via a catheter in the IVC of 11 swine. Filters remained in situ for 2 weeks (n = 2), 5 weeks (n = 2), 12 weeks (n = 2), 24 weeks (n = 2), and 32 weeks (n = 3). Autologous thrombus was administered from below the filter in seven swine from 0 to 35 days after filter placement. Fluoroscopy and computed tomography follow-up was performed after filter deployment from weeks 1-6 (weekly), weeks 7-20 (biweekly), and weeks 21-32 (monthly). The infrarenal IVC, lungs, heart, liver, kidneys, and spleen were harvested at necropsy. Continuous variables were evaluated with a Student t test. Results There was no evidence of IVC thrombosis, device migration, caval penetration, or pulmonary embolism. Gross pathologic analysis showed gradual device resorption until 32 weeks after deployment. Histologic assessment demonstrated neointimal hyperplasia around the IVC filter within 2 weeks after IVC filter deployment with residual microscopic fragments of polydioxanone suture within the caval wall at 32 weeks. Each iatrogenic-administered thrombus was successfully captured by the filter until resorbed (range, 1-4 weeks). Conclusion An absorbable IVC filter can be safely deployed in swine and resorbs gradually over the 32-week testing period. The device is effective for the prevention of pulmonary embolism for at least 5 weeks after placement in swine. © RSNA, 2017.

  15. Cutaneous varicella zoster virus infection following zoster vaccination: report of post-vaccination herpes zoster skin infection and literature review of zoster vaccination efficacy and guidelines.

    Science.gov (United States)

    Stiff, Katherine M; Cohen, Philip R

    2017-06-15

    BackgroundHerpes zoster vaccine is currently recommended in the United States for immune competent individuals ≥60 years. The efficacy of the herpes zoster vaccine decreases with age and with time following vaccination.PurposeAn elderly man with herpes zoster following vaccination is described. The guidelines for vaccination and issues regarding re-vaccination are reviewed. PubMed was used to search the following terms: efficacy, elderly, herpes zoster, herpes zoster incidence, herpes zoster recurrence, and vaccination. The papers and relevant citations were reviewed. The clinical features of a patient with post-vaccination herpes zoster skin infection are presented; in addition, vaccine efficacy and guidelines are reviewed.ResultsA 91-year-old man, vaccinated for herpes zoster 10 years earlier, presented with crusted erosions on his face corresponding to the area innervated by the ophthalmic division of the left trigeminal nerve. Evaluation using polymerase chain reaction confirmed the diagnosis of herpes zoster.ConclusionsHerpes zoster vaccine decreases in efficacy with both age and number of years following vaccination. Therefore, booster shots or revaccination in the older population may be of benefit.

  16. Leaky Vaccines Protect Highly Exposed Recipients at a Lower Rate: Implications for Vaccine Efficacy Estimation and Sieve Analysis

    Directory of Open Access Journals (Sweden)

    Paul T. Edlefsen

    2014-01-01

    Full Text Available “Leaky” vaccines are those for which vaccine-induced protection reduces infection rates on a per-exposure basis, as opposed to “all-or-none” vaccines, which reduce infection rates to zero for some fraction of subjects, independent of the number of exposures. Leaky vaccines therefore protect subjects with fewer exposures at a higher effective rate than subjects with more exposures. This simple observation has serious implications for analysis methodologies that rely on the assumption that the vaccine effect is homogeneous across subjects. We argue and show through examples that this heterogeneous vaccine effect leads to a violation of the proportional hazards assumption, to incomparability of infected cases across treatment groups, and to nonindependence of the distributions of the competing failure processes in a competing risks setting. We discuss implications for vaccine efficacy estimation, correlates of protection analysis, and mark-specific efficacy analysis (also known as sieve analysis.

  17. Leaky vaccines protect highly exposed recipients at a lower rate: implications for vaccine efficacy estimation and sieve analysis.

    Science.gov (United States)

    Edlefsen, Paul T

    2014-01-01

    "Leaky" vaccines are those for which vaccine-induced protection reduces infection rates on a per-exposure basis, as opposed to "all-or-none" vaccines, which reduce infection rates to zero for some fraction of subjects, independent of the number of exposures. Leaky vaccines therefore protect subjects with fewer exposures at a higher effective rate than subjects with more exposures. This simple observation has serious implications for analysis methodologies that rely on the assumption that the vaccine effect is homogeneous across subjects. We argue and show through examples that this heterogeneous vaccine effect leads to a violation of the proportional hazards assumption, to incomparability of infected cases across treatment groups, and to nonindependence of the distributions of the competing failure processes in a competing risks setting. We discuss implications for vaccine efficacy estimation, correlates of protection analysis, and mark-specific efficacy analysis (also known as sieve analysis).

  18. Rotavirus vaccines: safety, efficacy and public health impact.

    Science.gov (United States)

    Gray, J

    2011-09-01

    Rotaviruses are the cause of acute gastroenteritis, and disease is widespread amongst infants and young children throughout the world. Also, rotavirus is associated with significant mortality in developing countries with more than 500 000 children dying each year as a result of the severe dehydration associated with rotavirus disease. Efforts have been ongoing for more than 30 years to develop a safe and effective rotavirus vaccine. Currently, two vaccines, RotaRix and RotaTeq, have been licensed for use in many countries throughout the world following comprehensive safety and efficiency trials. Monitoring their effectiveness after licensure has confirmed that their incorporation into early childhood vaccination schedules can significantly prevent severe rotavirus diarrhoea, which would have resulted in hospitalizations, emergency room visits or increased diarrhoea-related mortality. Although the efficacy of both vaccines is lower at approximately 40-59% in developing countries, their use could significantly reduce the mortality associated with rotavirus disease that is concentrated in these countries. © 2011 The Association for the Publication of the Journal of Internal Medicine.

  19. Protection of guinea pigs by vaccination with a recombinant swinepox virus co-expressing HA1 genes of swine H1N1 and H3N2 influenza viruses.

    Science.gov (United States)

    Xu, Jiarong; Yang, Deji; Huang, Dongyan; Xu, Jiaping; Liu, Shichao; Lin, Huixing; Zhu, Haodan; Liu, Bao; Lu, Chengping

    2013-03-01

    Swine influenza (SI) is an acute respiratory infectious disease of swine caused by swine influenza virus (SIV). SIV is not only an important respiratory pathogen in pigs but also a potent threat to human health. Here, we report the construction of a recombinant swinepox virus (rSPV/H3-2A-H1) co-expressing hemagglutinin (HA1) of SIV subtypes H1N1 and H3N2. Immune responses and protection efficacy of the rSPV/H3-2A-H1 were evaluated in guinea pigs. Inoculation of rSPV/H3-2A-H1 yielded neutralizing antibodies against SIV H1N1 and H3N2. The IFN-γ and IL-4 concentrations in the supernatant of lymphocytes stimulated with purified SIV HA1 antigen were significantly higher (P guinea pigs against SIV H1N1 or H3N2 challenge was observed. No SIV shedding was detected from guinea pigs vaccinated with rSPV/H3-2A-H1 after challenge. Most importantly, the guinea pigs immunized with rSPV/H3-2A-H1 did not show gross and micrographic lung lesions. However, the control guinea pigs experienced distinct gross and micrographic lung lesions at 7 days post-challenge. Our data suggest that the recombinant swinepox virus encoding HA1 of SIV H1N1 and H3N2 might serve as a promising candidate vaccine for protection against SIV H1N1 and H3N2 infections.

  20. Genetic Diversity and Protective Efficacy of the RTS,S/AS01 Malaria Vaccine

    DEFF Research Database (Denmark)

    Neafsey, Daniel E; Juraska, Michal; Bedford, Trevor

    2015-01-01

    Background The RTS,S/AS01 vaccine targets the circumsporozoite protein of Plasmodium falciparum and has partial protective efficacy against clinical and severe malaria disease in infants and children. We investigated whether the vaccine efficacy was specific to certain parasite genotypes at the c......Background The RTS,S/AS01 vaccine targets the circumsporozoite protein of Plasmodium falciparum and has partial protective efficacy against clinical and severe malaria disease in infants and children. We investigated whether the vaccine efficacy was specific to certain parasite genotypes...... protein had on vaccine efficacy against first episodes of clinical malaria within 1 year after vaccination. Results In the per-protocol group of 4577 RTS,S/AS01-vaccinated participants and 2335 control-vaccinated participants who were 5 to 17 months of age, the 1-year cumulative vaccine efficacy was 50.......3% (95% confidence interval [CI], 34.6 to 62.3) against clinical malaria in which parasites matched the vaccine in the entire circumsporozoite protein C-terminal (139 infections), as compared with 33.4% (95% CI, 29.3 to 37.2) against mismatched malaria (1951 infections) (P=0.04 for differential vaccine...

  1. An E2-Substituted Chimeric Pestivirus With DIVA Vaccine Properties

    DEFF Research Database (Denmark)

    Rasmussen, Thomas Bruun; Uttenthal, Åse; Nielsen, Jens

    An advantage of the use of chimeric pestiviruses as modified live vaccines against classical swine fever (CSF) resides in their capacity to be manipulated to achieve the characteristics desired for safe and efficacious DIVA vaccines. We have recently generated a new chimeric virus, Riems26_E2gif...... vaccinated pigs were protected. This new chimeric pestivirus represents a C-strain based DIVA vaccine candidate that can be differentiated based on CSFV E2 specific antibodies....

  2. Efficacy and Safety of the RTS,S/AS01 Malaria Vaccine during 18 Months after Vaccination

    DEFF Research Database (Denmark)

    Theander, Thor Grundtvig; Lusingu, John Peter Andrea

    2014-01-01

    BACKGROUND: A malaria vaccine could be an important addition to current control strategies. We report the safety and vaccine efficacy (VE) of the RTS,S/AS01 vaccine during 18 mo following vaccination at 11 African sites with varying malaria transmission. METHODS AND FINDINGS: 6,537 infants aged 6......-12 wk and 8,923 children aged 5-17 mo were randomized to receive three doses of RTS,S/AS01 or comparator vaccine. VE against clinical malaria in children during the 18 mo after vaccine dose 3 (per protocol) was 46% (95% CI 42% to 50%) (range 40% to 77%; VE, p... after vaccine dose 1 (intention to treat [ITT]) was 45% (95% CI 41% to 49%). VE against severe malaria, malaria hospitalization, and all-cause hospitalization was 34% (95% CI 15% to 48%), 41% (95% CI 30% to 50%), and 19% (95% CI 11% to 27%), respectively (ITT). VE against clinical malaria in infants...

  3. Uncovering of Classical Swine Fever Virus adaptive response to vaccination by Next Generation Sequencing

    DEFF Research Database (Denmark)

    Fahnøe, Ulrik; Orton, Richard; Höper, Dirk

    Next Generation Sequencing (NGS) has rapidly become the preferred technology in nucleotide sequencing, and can be applied to unravel molecular adaptation of RNA viruses such as Classical Swine Fever Virus (CSFV). However, the detection of low frequency variants within viral populations by NGS...... is affected by errors introduced during sample preparation and sequencing, and so far no definitive solution to this problem has been presented....

  4. Gradual development of the interferon-γ response of swine to porcine reproductive and respiratory syndrome virus infection or vaccination

    International Nuclear Information System (INIS)

    Meier, William A.; Galeota, Judy; Osorio, Fernando A.; Husmann, Robert J.; Schnitzlein, William M.; Zuckermann, Federico A.

    2003-01-01

    Infection of swine with virulent porcine reproductive and respiratory syndrome (PRRS) virus induced a rapid, robust antibody response that comprised predominantly nonneutralizing antibodies and waned after approximately 3 months. In contrast, the initial onset of virus-specific interferon (IFN)-γ-secreting cells (SC) in the pig lymphocyte population remained at a fairly low level during this period and then increased gradually in frequency, plateauing at 6 months postinfection. A similar polarization of the host humoral and cellular immune responses was also observed in pigs immunized with a PRRS-modified live virus (MLV) vaccine. Even coadministration of an adjuvant that enhanced the immune response to a pseudorabies (PR) MLV vaccine failed to alter the induction of PRRS virus-specific IFN-γ SC (comprising predominately CD4/CD8α double positive memory T cells with a minority being typical CD4 - /CD8αβ + T cells) and the generation of neutralizing antibodies. Moreover, unlike inactivated PR virus, nonviable PRRS virus did not elicit virus-neutralizing antibody production. Presumably, an intrinsic property of this pathogen delays the development of the host IFN-γ response and preferentially stimulates the synthesis of antibodies incapable of neutralization

  5. A proposed framework for evaluating and comparing efficacy estimates in clinical trials of new rotavirus vaccines.

    Science.gov (United States)

    Neuzil, Kathleen M; Zaman, K; Victor, John C

    2014-08-11

    Oral rotavirus vaccines have yielded different point estimates of efficacy when tested in different populations. While population and environmental factors may account for these differences, study design characteristics should also be considered. We review the study design elements of rotavirus vaccine trials that may affect point estimates of efficacy, and propose a framework for evaluating new rotavirus vaccines. Copyright © 2014. Published by Elsevier Ltd.

  6. Efficacy in the field of two anticoccidial vaccines for broilers

    Directory of Open Access Journals (Sweden)

    Guido Grilli

    2010-01-01

    Full Text Available We compared two attenuated anticoccidial vaccines, administered to broilers by spray into the incubator (88,000 males and 210,100 females. Vaccine A container five species of Eimeria and vaccine B three. Zootechnical performance was similar in the two groups, with mean lesion scores no higher than 1; vaccine A caused only duodenal lesions, while vaccine B also caused typhlitis. Maximum oocyst count was 23,000/g feces at age 28 days with vaccine A and 38,000 at 21 days with vaccine B. Broilers vaccinated with vaccine B had more frequent enteric symptoms, and C. perfringens isolation.

  7. Strategies to Improve Vaccine Efficacy against Tuberculosis by Targeting Innate Immunity

    Directory of Open Access Journals (Sweden)

    Ulrich E. Schaible

    2017-12-01

    Full Text Available The global tuberculosis epidemic is the most common cause of death after infectious disease worldwide. Increasing numbers of infections with multi- and extensively drug-resistant variants of the Mycobacterium tuberculosis complex, resistant even to newly discovered and last resort antibiotics, highlight the urgent need for an efficient vaccine. The protective efficacy to pulmonary tuberculosis in adults of the only currently available vaccine, M. bovis BCG, is unsatisfactory and geographically diverse. More importantly, recent clinical studies on new vaccine candidates did not prove to be better than BCG, yet. Here, we propose and discuss novel strategies to improve efficacy of existing anti-tuberculosis vaccines. Modulation of innate immune responses upon vaccination already provided promising results in animal models of tuberculosis. For instance, neutrophils have been shown to influence vaccine efficacy, both, positively and negatively, and stimulate specific antibody secretion. Modulating immune regulatory properties after vaccination such as induction of different types of innate immune cell death, myeloid-derived suppressor or regulatory T cells, production of anti-inflammatory cytokines such as IL-10 may have beneficial effects on protection efficacy. Incorporation of lipid antigens presented via CD1 molecules to T cells have been discussed as a way to enhance vaccine efficacy. Finally, concepts of dendritic cell-based immunotherapies or training the innate immune memory may be exploitable for future vaccination strategies against tuberculosis. In this review, we put a spotlight on host immune networks as potential targets to boost protection by old and new tuberculosis vaccines.

  8. Impact of Dengue Vaccination on Serological Diagnosis: Insights From Phase III Dengue Vaccine Efficacy Trials.

    Science.gov (United States)

    Plennevaux, Eric; Moureau, Annick; Arredondo-García, José L; Villar, Luis; Pitisuttithum, Punnee; Tran, Ngoc H; Bonaparte, Matthew; Chansinghakul, Danaya; Coronel, Diana L; L'Azou, Maïna; Ochiai, R Leon; Toh, Myew-Ling; Noriega, Fernando; Bouckenooghe, Alain

    2018-04-03

    We previously reported that vaccination with the tetravalent dengue vaccine (CYD-TDV; Dengvaxia) may bias the diagnosis of dengue based on immunoglobulin M (IgM) and immunoglobulin G (IgG) assessments. We undertook a post hoc pooled analysis of febrile episodes that occurred during the active surveillance phase (the 25 months after the first study injection) of 2 pivotal phase III, placebo-controlled CYD-TDV efficacy studies that involved ≥31000 children aged 2-16 years across 10 countries in Asia and Latin America. Virologically confirmed dengue (VCD) episode was defined with a positive test for dengue nonstructural protein 1 antigen or dengue polymerase chain reaction. Probable dengue episode was serologically defined as (1) IgM-positive acute- or convalescent-phase sample, or (2) IgG-positive acute-phase sample and ≥4-fold IgG increase between acute- and convalescent-phase samples. There were 1284 VCD episodes (575 and 709 in the CYD-TDV and placebo groups, respectively) and 17673 other febrile episodes (11668 and 6005, respectively). Compared with VCD, the sensitivity and specificity of probable dengue definition were 93.1% and 77.2%, respectively. Overall positive and negative predictive values were 22.9% and 99.5%, respectively, reflecting the much lower probability of correctly confirming probable dengue in a population including a vaccinated cohort. Vaccination-induced bias toward false-positive diagnosis was more pronounced among individuals seronegative at baseline. Caution will be required when interpreting IgM and IgG data obtained during routine surveillance in those vaccinated with CYD-TDV. There is an urgent need for new practical, dengue-specific diagnostic algorithms now that CYD-TDV is approved in a number of dengue-endemic countries. NCT01373281 and NCT01374516.

  9. Effects of Message Framing on Influenza Vaccination: Understanding the Role of Risk Disclosure, Perceived Vaccine Efficacy, and Felt Ambivalence.

    Science.gov (United States)

    Kim, Sungsu; Pjesivac, Ivanka; Jin, Yan

    2017-10-20

    The current study examined the effects of framing in promotional health messages on intention to vaccinate against seasonal influenza virus. The findings of an experimental study (N = 86) indicated that exposure to both benefits and side effects of vaccination (gain-framed with risk disclosure message) led to lower intention to receive the flu vaccine. This relationship was mediated by both perceived vaccine efficacy and felt ambivalence in a serial order, revealing the underlying psychological mechanisms important for understanding health-related behaviors. Theoretical implications of constructing sub-framed messages are discussed and the concept of second-order framing is introduced.

  10. Antigen-Sparing and Enhanced Efficacy of Multivalent Vaccines Adjuvanted with Immunopotentiators in Chickens

    Directory of Open Access Journals (Sweden)

    Peipei Wu

    2017-05-01

    Full Text Available We previously described that immunopotentiators, CVCVA5, increased the efficacy of H5 and H9 subtype avian influenza vaccines in chickens, ducks, and geese. In this study, we further investigated the effects of the CVCVA5 for improving the efficacy of other univalent or multivalent inactivated vaccines. The immune response administrated with half-dose of monovalent vaccine plus CVCVA5 were higher than those of one dose of monovalent vaccine without immunopotentiators as measured by levels of antibodies from serum, tears and bronchoalveolar lavage fluids, and cytokines of IFNγ and IL-4 from serum. Vaccines included the univalent vaccine of Newcastle Disease virus (ND, Egg Drop Syndrome virus (EDS, Infectious Bronchitis virus (IB, and Infectious Bursal Disease virus (IBD. The CVCVA5 also improved the immune response of both ND and IBD vaccines with less dosage. The sterile protective immunity was monitored with one- or a half-dose of adjuvanted ND vaccine or one dose of adjuvanted IBD vaccine, respectively. The improved immune efficacy was observed in a half-dose of adjuvanted bivalent vaccines compared to one dose of vaccines without CVCVA5 as measured by the antibody levels, including bivalent vaccine of ND-H9, ND-IB, and ND-IBD. The CVCVA5 also boosted the immune efficacy of the tetravalent vaccine (ND-IB-EDS-H9. A half-dose of adjuvanted commercial vaccine or 75% antigen-sparing adjuvanted vaccine elicited similar antibody levels to those of one dose non-adjuvanted commercial vaccines. The CVCVA5 improved the effect of a booster vaccination as measured by the antibody levels against H5 or H9 virus antigens, in which chickens primed with the adjuvanted ND-IB vaccines given a booster with H5–H9 bivalent vaccines without CVCVA5 using 5-day intervals. The inflammatory response may contribute to these additional effects by increasing the levels of IFNγ and IL-4 after the injection of the adjuvanted ND-IB vaccines. Results indicated that the

  11. Hemagglutinating virus of Japan envelope (HVJ-E) can enhance the immune responses of swine immunized with killed PRRSV vaccine

    Energy Technology Data Exchange (ETDEWEB)

    Dai, Zhihong [State Key Laboratory of Agrobiotechnology, College of Veterinary Medicine, China Agricultural University, Beijing 100094 (China); China Institute of Veterinary Drug Control, Beijing 100081 (China); Zhang, Quan [College of Veterinary Medicine, Yangzhou University, Yangzhou 225009 (China); Wang, Zaishi [China Institute of Veterinary Drug Control, Beijing 100081 (China); Zhang, Zhongqiu [State Key Laboratory of Agrobiotechnology, College of Veterinary Medicine, China Agricultural University, Beijing 100094 (China); Veterinary Bureau, Ministry of Agriculture of the People' s Republic of China, Beijing 100125 (China); Guo, Pengju [Institute of Veterinary Medicine, Guangdong Academy of Agricultural Sciences, Guangdong 510640 (China); Zhao, Deming, E-mail: zhaodm@cau.edu.cn [State Key Laboratory of Agrobiotechnology, College of Veterinary Medicine, China Agricultural University, Beijing 100094 (China)

    2011-11-11

    Highlights: Black-Right-Pointing-Pointer We investigated the immunoadjuvant effects of HVJ-E on killed PRRSV vaccine. Black-Right-Pointing-Pointer HVJ-E enhanced the humoral and cellular responses of the piglets to PRRSV. Black-Right-Pointing-Pointer It is suggested that HVJ-E could be developed as a new-type adjuvant for mammals. -- Abstract: Porcine reproductive and respiratory syndrome virus (PRRSV) is an economically detrimental pig pathogen that causes significant losses for the pig industry. The immunostimulatory effects of hemagglutinating virus of Japan envelope (HVJ-E) in cancer therapy and the adjuvant efficacy of HVJ-E have been previously evaluated. The objective of this study was to investigate the adjuvant effects of HVJ-E on immunization with killed PRRSV vaccine, and to evaluate the protective effects of this immunization strategy against virulent PRRSV infection in piglets. Next, the PRRSV-specific antibody response, lymphocyte proliferation, PRRSV-specific IL-2, IL-10 and IFN-{gamma} production, and the overall protection efficacy were evaluated to assess the immune responses of the piglets. The results showed that the piglets inoculated simultaneously with killed PRRSV vaccine and HVJ-E had a significantly stronger immune response than those inoculated with killed PRRSV vaccine alone. Our results suggest that HVJ-E could be employed as an effective adjuvant to enhance the humoral and cellular responses of piglets to PRRSV.

  12. Shape of Key Malaria Protein Could Help Improve Vaccine Efficacy

    Science.gov (United States)

    ... Featured Diseases & Conditions Food Allergy HIV/AIDS Influenza Malaria Respiratory Syncytial Virus (RSV) Tuberculosis Zika Virus Find ... To Volunteer for Vaccine Research Studies Volunteer for Malaria Vaccine Research Volunteer Profiles Q&A: Vaccine Clinical ...

  13. Flu Vaccine Safety Information

    Science.gov (United States)

    ... Influenza Types Seasonal Avian Swine Variant Pandemic Other Flu Vaccine Safety Information Questions & Answers Language: English (US) ... safety of flu vaccines monitored? Egg Allergy Are flu vaccines safe? Flu vaccines have good safety record. ...

  14. Thimerosal in Flu Vaccine

    Science.gov (United States)

    ... Seasonal Avian Swine Variant Pandemic Other Thimerosal in Flu Vaccine Questions & Answers Language: English (US) Español Recommend ... and/or fungi from contaminating the vaccine. Do flu vaccines contain thimerosal? Flu vaccines in multi-dose ...

  15. A novel recombinant pseudorabies virus expressing parvovirus VP2 gene: Immunogenicity and protective efficacy in swine.

    Science.gov (United States)

    Chen, Yang; Guo, Wanzhu; Xu, Zhiwen; Yan, Qigui; Luo, Yan; Shi, Qian; Chen, Dishi; Zhu, Ling; Wang, Xiaoyu

    2011-06-16

    Porcine parvovirus (PPV) VP2 gene has been successfully expressed in many expression systems resulting in self-assembly of virus-like particles (VLPs) with similar morphology to the native capsid. Here, a pseudorabies virus (PRV) system was adopted to express the PPV VP2 gene. A recombinant PRV SA215/VP2 was obtained by homologous recombination between the vector PRV viral DNA and a transfer plasmid. Then recombinant virus was purified with plaque purification, and its identity confirmed by PCR amplification, Western blot and indirect immunofluorescence (IFA) analyses. Electronic microscopy of PRV SA215/VP2 confirmed self-assembly of both pseudorabies virus and VLPs from VP2 protein. Immunization of piglets with recombinant virus elicited PRV-specific and PPV-specific humoral immune responses and provided complete protection against a lethal dose of PRV challenges. Gilts immunized with recombinant viruses induced PPV-specific antibodies, and significantly reduced the mortality rate of (1 of 28) following virulent PPV challenge compared with the control (7 of 31). Furthermore, PPV virus DNA was not detected in the fetuses of recombinant virus immunized gilts. In this study, a recombinant PRV SA215/VP2 virus expressing PPV VP2 protein was constructed using PRV SA215 vector. The safety, immunogenicity, and protective efficacy of the recombinant virus were demonstrated in piglets and primiparous gilts. This recombinant PRV SA215/VP2 represents a suitable candidate for the development of a bivalent vaccine against both PRV and PPV infection.

  16. Field evaluation of the efficacy of Mycobacterium bovis BCG vaccine against tuberculosis in goats.

    Science.gov (United States)

    Vidal, Enric; Arrieta-Villegas, Claudia; Grasa, Miriam; Mercader, Irene; Domingo, Mariano; Pérez de Val, Bernat

    2017-08-17

    Control of animal tuberculosis (TB) through vaccination has emerged as a long-term strategy to complement test and slaughter control strategy. A pilot trial under field conditions was conducted in a goat herd with high TB prevalence to assess the efficacy of the Mycobacterium bovis BCG vaccine. Twenty-three goat kids vaccinated with BCG and other 22 unvaccinated control kids were euthanized at 18 months post-vaccination. Gross pathological and histopathological examination of target tissues was performed for detection of tuberculous lesions and assessment of vaccine efficacy. Mycobacterial culture and DNA detection were used to confirm Mycobacterium caprae infection. Vaccination significantly reduced the number of animals with TB lesions compared to unvaccinated controls (35% and 77%, respectively; P goats can significantly reduce the TB lesion rates in high disease exposure conditions, indicating that vaccination could contribute to the control of TB in domestic goats.

  17. World association for the advancement of veterinary parasitology (WAAVP): Second edition of guidelines for evaluating the efficacy of anthelmintics in swine

    DEFF Research Database (Denmark)

    Hennessy, D.R.; Bauer, C.; Boray, J.C.

    2006-01-01

    Guidelines are provided for evaluating the efficacy of anthelmintics in swine which, in conjunction with other sets of guidance such as those of the International Cooperation on Harmonization of Technical Requirements for Registration of Veterinary Medicinal Products (VICH GL7 and VICH GL16), sho...

  18. The effect of age and recent influenza vaccination history on the immunogenicity and efficacy of 2009-10 seasonal trivalent inactivated influenza vaccination in children.

    Directory of Open Access Journals (Sweden)

    Sophia Ng

    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.

  19. A randomized controlled study on the efficacy of a novel combination vaccine against enzootic pneumonia (Mycoplasma hyopneumoniae) and porcine Circovirus type 2 (PCV2) in the presence of strong maternally derived PCV2 immunity in pigs.

    Science.gov (United States)

    Tassis, Panagiotis D; Tsakmakidis, Ioannis; Papatsiros, Vassileios G; Koulialis, Dimitrios; Nell, Tom; Brellou, Georgia; Tzika, Eleni D

    2017-04-07

    Mycoplasma hyopneumoniae (M. hyo) and Porcine Circovirus Type 2 (PCV2) are major pathogens that cause significant health problems in swine worldwide. Maternal derived immunity (MDI) has been suggested as a significant immediate defence factor for newborn piglets and may interfere with piglet's vaccination-induced immunity. The study aimed to assess the efficacy of a novel combination vaccine (consisting of PCV2 subunits and inactivated M. hyo strain J), against PCV2 and M. hyo natural infection [Porcilis ® PCV M Hyo (MSD Animal Health, Boxmeer, the Netherlands)], in the presence of strong maternally derived PCV2 immunity (antibody titre averaged 11.08 log 2 ), under field conditions. The study was performed according to a controlled, randomized and blinded design in a Greek swine unit with Enzootic Pneumonia (EP) and subclinical PCV2 infection. In total, 600 healthy three-week-old suckling piglets were allocated randomly, either to treatment (vaccinated with the test product) or control group (injected with sterile buffered saline). Vaccination significantly reduced the severity of lung lesions at slaughter (lesions of cranio-ventral pulmonary consolidation) (P pigs. Furthermore, 25 g higher average daily weight gain (ADWG) was observed during the finishing phase (P < 0.001) and 18 g greater ADWG overall (P < 0.001). Results of LLS, PCV2 viremia and ADWG support the test product's efficacy in the face of strong maternally derived PCV2 immunity.

  20. A novel recombinant pseudorabies virus expressing parvovirus VP2 gene: Immunogenicity and protective efficacy in swine

    Directory of Open Access Journals (Sweden)

    Chen Dishi

    2011-06-01

    Full Text Available Abstract Background Porcine parvovirus (PPV VP2 gene has been successfully expressed in many expression systems resulting in self-assembly of virus-like particles (VLPs with similar morphology to the native capsid. Here, a pseudorabies virus (PRV system was adopted to express the PPV VP2 gene. Methods A recombinant PRV SA215/VP2 was obtained by homologous recombination between the vector PRV viral DNA and a transfer plasmid. Then recombinant virus was purified with plaque purification, and its identity confirmed by PCR amplification, Western blot and indirect immunofluorescence (IFA analyses. Electronic microscopy of PRV SA215/VP2 confirmed self-assembly of both pseudorabies virus and VLPs from VP2 protein. Results Immunization of piglets with recombinant virus elicited PRV-specific and PPV-specific humoral immune responses and provided complete protection against a lethal dose of PRV challenges. Gilts immunized with recombinant viruses induced PPV-specific antibodies, and significantly reduced the mortality rate of (1 of 28 following virulent PPV challenge compared with the control (7 of 31. Furthermore, PPV virus DNA was not detected in the fetuses of recombinant virus immunized gilts. Conclusions In this study, a recombinant PRV SA215/VP2 virus expressing PPV VP2 protein was constructed using PRV SA215 vector. The safety, immunogenicity, and protective efficacy of the recombinant virus were demonstrated in piglets and primiparous gilts. This recombinant PRV SA215/VP2 represents a suitable candidate for the development of a bivalent vaccine against both PRV and PPV infection.

  1. Efficacy demonstration of tetanus vaccines by double antigen ELISA.

    Science.gov (United States)

    Rosskopf, U; Noeske, K; Werner, E

    2005-09-01

    This paper describes a double antigen ELISA (DAE) for rapid, specific and reliable assessment of the antitetanus immune status of horses and sheep. Compared with the indirect ELISA, the double antigen ELISA has the advantage of species-independent testing of sera. Thanks to its test design, it is more specific since the detected antibodies are forced to bind tetanus toxoid twice. In addition, it is very sensitive to tetanus antibodies, enabling the detection of low antibody titres, in range which is relevant for the assessment of the protective status (tetanus toxin neutralising antibodies). The detection limit of the DAE for tetanus antibodies is in the order of 10(-4) EU/ml. A comparison of in vitro results of individual sera with in vivo titres showed that horse sera with titres of 0.04 and 0.05 EU/ml in the DAE showed titres of > 0.05 IU and 0.034 IU/ml respectively during in vivo testing thus indicating good agreement. For tested sheep sera which were rated > 0.05 IU/ml in vivo, the corresponding titre in the DAE was 0.24 EU/ml. Clear tetanus antitoxin establishment of protective ELISA limits requires further comparative examination of sera with low titres (tetanus vaccines ad us. vet. As a consequence, the toxin neutralisation test (still being the standard method of choice for quantifying tetanus toxin neutralising antitoxin titres) could be replaced, since it requires too great a number of animals per test and involves considerable suffering for the animals. The test described here reduces the use of mice and guinea pigs within vaccine efficacy testing. In addition, it involves less exposure of the laboratory personnel to toxin.

  2. Efficacy of a tetravalent dengue vaccine in children in Latin America.

    Science.gov (United States)

    Villar, Luis; Dayan, Gustavo Horacio; Arredondo-García, José Luis; Rivera, Doris Maribel; Cunha, Rivaldo; Deseda, Carmen; Reynales, Humberto; Costa, Maria Selma; Morales-Ramírez, Javier Osvaldo; Carrasquilla, Gabriel; Rey, Luis Carlos; Dietze, Reynaldo; Luz, Kleber; Rivas, Enrique; Miranda Montoya, Maria Consuelo; Cortés Supelano, Margarita; Zambrano, Betzana; Langevin, Edith; Boaz, Mark; Tornieporth, Nadia; Saville, Melanie; Noriega, Fernando

    2015-01-08

    In light of the increasing rate of dengue infections throughout the world despite vector-control measures, several dengue vaccine candidates are in development. In a phase 3 efficacy trial of a tetravalent dengue vaccine in five Latin American countries where dengue is endemic, we randomly assigned healthy children between the ages of 9 and 16 years in a 2:1 ratio to receive three injections of recombinant, live, attenuated, tetravalent dengue vaccine (CYD-TDV) or placebo at months 0, 6, and 12 under blinded conditions. The children were then followed for 25 months. The primary outcome was vaccine efficacy against symptomatic, virologically confirmed dengue (VCD), regardless of disease severity or serotype, occurring more than 28 days after the third injection. A total of 20,869 healthy children received either vaccine or placebo. At baseline, 79.4% of an immunogenicity subgroup of 1944 children had seropositive status for one or more dengue serotypes. In the per-protocol population, there were 176 VCD cases (with 11,793 person-years at risk) in the vaccine group and 221 VCD cases (with 5809 person-years at risk) in the control group, for a vaccine efficacy of 60.8% (95% confidence interval [CI], 52.0 to 68.0). In the intention-to-treat population (those who received at least one injection), vaccine efficacy was 64.7% (95% CI, 58.7 to 69.8). Serotype-specific vaccine efficacy was 50.3% for serotype 1, 42.3% for serotype 2, 74.0% for serotype 3, and 77.7% for serotype 4. Among the severe VCD cases, 1 of 12 was in the vaccine group, for an intention-to-treat vaccine efficacy of 95.5%. Vaccine efficacy against hospitalization for dengue was 80.3%. The safety profile for the CYD-TDV vaccine was similar to that for placebo, with no marked difference in rates of adverse events. The CYD-TDV dengue vaccine was efficacious against VCD and severe VCD and led to fewer hospitalizations for VCD in five Latin American countries where dengue is endemic. (Funded by Sanofi Pasteur

  3. CYD-TDV dengue vaccine: systematic review and meta-analysis of efficacy, immunogenicity and safety.

    Science.gov (United States)

    Godói, Isabella Piassi; Lemos, Livia Lovato Pires; de Araújo, Vânia Eloisa; Bonoto, Braúlio Cesar; Godman, Brian; Guerra Júnior, Augusto Afonso

    2017-03-01

    Dengue virus (DENV) is a serious global health problem. CYD-TDC (Dengvaxia ® ) was the first vaccine to gain regulatory approval to try and address this problem. Summarize all available evidence on the immunogenicity, efficacy and safety of the CYD-TDV dengue vaccine. Meta-analysis and systematic review. The best and worst immunogenicity results were for DENV4 and DENV1, respectively. Vaccine efficacy of 60% was derived from studies with participants aged 2-16 years old, with DENV4 and DENV2 presenting the best and worst results, respectively. Erythema and swelling were more frequent with CYD-TDV. No differences were detected for systemic adverse events. CYD-TDV showed moderate efficacy in children and adolescents. From the immunogenicity results in adults, we can expect satisfactory efficacy from vaccination in this population.

  4. Biological and phylogenetic characterization of a genotype VII Newcastle disease virus from Venezuela: Efficacy of vaccination

    Science.gov (United States)

    Here we describe the characterization a virulent genotype VII Newcastle disease virus (NDV) from Venezuela and evaluate the efficacy of heterologous genotype commercial vaccination under field and controlled rearing conditions. Biological pathotyping and molecular analysis were applied. Results sh...

  5. The Evidence for Efficacy of HPV Vaccines: Investigations in Categorical Data Analysis

    Science.gov (United States)

    Gibbs, Alison L.; Goossens, Emery T.

    2013-01-01

    Recent approval of HPV vaccines and their widespread provision to young women provide an interesting context to gain experience with the application of statistical methods in current research. We demonstrate how we have used data extracted from a meta-analysis examining the efficacy of HPV vaccines in clinical trials with students in applied…

  6. An experimental Toxoplasma gondii dose response challenge model to study therapeutic or vaccine efficacy in cats

    NARCIS (Netherlands)

    Cornelissen, J.B.W.J.; Giessen, van der J.W.B.; Takumi, K.; Teunis, P.F.M.; Wisselink, H.J.

    2014-01-01

    High numbers of Toxoplasma gondii oocysts in the environment are a risk factor to humans. The environmental contamination might be reduced by vaccinating the definitive host, cats. An experimental challenge model is necessary to quantitatively assess the efficacy of a vaccine or drug treatment.

  7. Characterisation of vaccine-induced, broadly cross-reactive IFN-γ secreting T cell responses that correlate with rapid protection against classical swine fever virus.

    Science.gov (United States)

    Graham, Simon P; Haines, Felicity J; Johns, Helen L; Sosan, Olubukola; La Rocca, S Anna; Lamp, Benjamin; Rümenapf, Till; Everett, Helen E; Crooke, Helen R

    2012-04-05

    Live attenuated C-strain classical swine fever viruses (CSFV) provide a rapid onset of protection, but the lack of a serological test that can differentiate vaccinated from infected animals limits their application in CSF outbreaks. Since immunity may precede antibody responses, we examined the kinetics and specificity of peripheral blood T cell responses from pigs vaccinated with a C-strain vaccine and challenged after five days with a genotypically divergent CSFV isolate. Vaccinated animals displayed virus-specific IFN-γ responses from day 3 post-challenge, whereas, unvaccinated challenge control animals failed to mount a detectable response. Both CD4(+) and cytotoxic CD8(+) T cells were identified as the cellular source of IFN-γ. IFN-γ responses showed extensive cross-reactivity when T cells were stimulated with CSFV isolates spanning the major genotypes. To determine the specificity of these responses, T cells were stimulated with recombinant CSFV proteins and a proteome-wide peptide library from a related virus, BVDV. Major cross-reactive peptides were mapped on the E2 and NS3 proteins. Finally, IFN-γ was shown to exert potent antiviral effects on CSFV in vitro. These data support the involvement of broadly cross-reactive T cell IFN-γ responses in the rapid protection conferred by the C-strain vaccine and this information should aid the development of the next generation of CSFV vaccines. Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.

  8. Evaluation of protective efficacy of three novel H3N2 canine influenza vaccines.

    Science.gov (United States)

    Tu, Liqing; Zhou, Pei; Li, Lutao; Li, Xiuzhen; Hu, Renjun; Jia, Kun; Sun, Lingshuang; Yuan, Ziguo; Li, Shoujun

    2017-11-17

    Canine influenza virus (CIV) has the potential risk to spread in different areas and dog types. Thus, there is a growing need to develop an effective vaccine to control CIV disease. Here, we developed three vaccine candidates: 1) a recombinant pVAX1 vector expressing H3N2 CIV hemagglutinin (pVAX1-HA); 2) a live attenuated canine adenovirus type 2 expressing H3N2 CIV hemagglutinin (rCAV2-HA); and 3) an inactivated H3N2 CIV (A/canine/Guangdong/01/2006 (H3N2)). Mice received an initial intramuscular immunization that followed two booster injections at 2 and 4 weeks post-vaccination (wpv). The splenic lymphocytes were collected to assess the immune responses at 6 wpv. The protective efficacy was evaluated by challenging H3N2 CIV after vaccination (at 6 wpv). Our results demonstrated that all three vaccine candidates elicited cytokine and antibody responses in mice. The rCAV2-HA vaccine and the inactivated vaccine generated efficient protective efficacy in mice, whereas limited protection was provided by the pVAX1-HA DNA vaccine. Therefore, both the rCAV2-HA live recombinant virus and the inactivated CIV could be used as potential novel vaccines against H3N2CIV. This study provides guidance for choosing the most appropriate vaccine for the prevention and control of CIV disease.

  9. Advancing Toward HIV-1 Vaccine Efficacy through the Intersections of Immune Correlates

    Directory of Open Access Journals (Sweden)

    Georgia D. Tomaras

    2013-12-01

    Full Text Available Interrogating immune correlates of infection risk for efficacious and non-efficacious HIV-1 vaccine clinical trials have provided hypotheses regarding the mechanisms of induction of protective immunity to HIV-1. To date, there have been six HIV-1 vaccine efficacy trials (VAX003, Vaxgen, Inc., San Francisco, CA, USA, VAX004 (Vaxgen, Inc., HIV-1 Vaccine Trials Network (HVTN 502 (Step, HVTN 503 (Phambili, RV144 (sponsored by the U.S. Military HIV Research Program, MHRP and HVTN 505. Cellular, humoral, host genetic and virus sieve analyses of these human clinical trials each can provide information that may point to potentially protective mechanisms for vaccine-induced immunity. Critical to staying on the path toward development of an efficacious vaccine is utilizing information from previous human and non-human primate studies in concert with new discoveries of basic HIV-1 host-virus interactions. One way that past discoveries from correlate analyses can lead to novel inventions or new pathways toward vaccine efficacy is to examine the intersections where different components of the correlate analyses overlap (e.g., virus sieve analysis combined with humoral correlates that can point to mechanistic hypotheses. Additionally, differences in durability among vaccine-induced T- and B-cell responses indicate that time post-vaccination is an important variable. Thus, understanding the nature of protective responses, the degree to which such responses have, or have not, as yet, been induced by previous vaccine trials and the design of strategies to induce durable T- and B-cell responses are critical to the development of a protective HIV-1 vaccine.

  10. Effect of acute aerobic exercise on vaccine efficacy in older adults.

    Science.gov (United States)

    Ranadive, Sushant Mohan; Cook, Marc; Kappus, Rebecca Marie; Yan, Huimin; Lane, Abbi Danielle; Woods, Jeffery A; Wilund, Kenneth R; Iwamoto, Gary; Vanar, Vishwas; Tandon, Rudhir; Fernhall, Bo

    2014-03-01

    The most effective way of avoiding influenza is through influenza vaccination. However, the vaccine is ineffective in about 25% of the older population. Immunosenescence with advancing age results in inadequate protection from disease because of ineffective responses to vaccination. Recently, a number of strategies have been tested to improve the efficacy of a vaccine in older adults. An acute bout of moderate aerobic exercise may increase the efficacy of the vaccine in young individuals, but there are limited efficacy data in older adults who would benefit most. This study sought to evaluate whether acute moderate-intensity endurance exercise immediately before influenza vaccination would increase the efficacy of the vaccine. Fifty-nine healthy volunteers between 55 and 75 yr of age were randomly allocated to an exercise or control group. Antibody titers were measured at baseline before exercise and 4 wk after vaccination. C-reactive protein (CRP) and interleukin-6 (IL-6) were measured at 24 and 48 h after vaccination. Delta CRP and IL-6 at 24 and 48 h were significantly higher after vaccination as compared to the sham injection. There were no differences in the levels of antibody titers against the H3N2 influenza strain between groups. However, women in the exercise group had a significantly higher antibody response against the H1N1 influenza strain as compared to the men, probably because of lower prevaccine titers. There were no significant differences in seroprotection between groups. Acute moderate aerobic exercise was not immunostimulatory in healthy older men but may serve as a vaccine adjuvant in older women.

  11. Prevention of rotavirus gastroenteritis in infants and children: rotavirus vaccine safety, efficacy, and potential impact of vaccines

    Directory of Open Access Journals (Sweden)

    Aruna Chandran

    2010-07-01

    Full Text Available Aruna Chandran1, Sean Fitzwater1, Anjie Zhen2, Mathuram Santosham11Department of International Health, Division of Health Systems, 2Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USAAbstract: Rotavirus infection is the most common cause of severe gastroenteritis globally, with greater than 86% of deaths occurring in low-income and middle-income countries. There are two rotavirus vaccines currently licensed in the United States and prequalified by the World Health Organization. RV1 is a monovalent attenuated human rotavirus strain, given orally in two doses. RV5 is a pentavalent human-bovine reassortant rotavirus vaccine, given orally in three doses. A third rotavirus vaccine, LLV, is a lamb rotavirus strain given orally as a single dose, which is currently available only in China. RV1 and RV5 have been shown to be highly efficacious in developed countries, and initial results from trials in Africa and Asia are promising as well. At least three other vaccines are in development, which are being developed by manufacturers of developing countries. Further studies are needed to clarify issues including administration of oral rotavirus vaccines with breastfeeding and other oral vaccines, and alterations in dosing schedule. Using new data on global diarrheal burden, rotavirus is estimated to cause 390,000 deaths in children younger than 5 years. Should rotavirus vaccines be introduced in the routine immunization programs of all countries, a potential of 170,000 deaths could be prevented annually. The largest impact on mortality would be seen in low-income and middle-income countries, despite poor immunization coverage and lower efficacy. Therefore, international efforts are needed to ensure that rotavirus vaccines reach the populations with highest burden of rotavirus disease.Keywords: vaccination, mortality, rotavirus, gastroenteritis

  12. Swine influenza and vaccines: an alternative approach for decision making about pandemic prevention.

    Science.gov (United States)

    Basili, Marcello; Ferrini, Silvia; Montomoli, Emanuele

    2013-08-01

    During the global pandemic of A/H1N1/California/07/2009 (A/H1N1/Cal) influenza, many governments signed contracts with vaccine producers for a universal influenza immunization program and bought hundreds of millions of vaccines doses. We argue that, as Health Ministers assumed the occurrence of the worst possible scenario (generalized pandemic influenza) and followed the strong version of the Precautionary Principle, they undervalued the possibility of mild or weak pandemic wave. An alternative decision rule, based on the non-extensive entropy principle, is introduced, and a different Precautionary Principle characterization is applied. This approach values extreme negative results (catastrophic events) in a different way and predicts more plausible and mild events. It introduces less pessimistic forecasts in the case of uncertain influenza pandemic outbreaks. A simplified application is presented using seasonal data of morbidity and severity among Italian children influenza-like illness for the period 2003-10. Established literature results predict an average attack rate of not less than 15% for the next pandemic influenza [Meltzer M, Cox N, Fukuda K. The economic impact of pandemic influenza in the United States: implications for setting priorities for interventions. Emerg Infect Dis 1999;5:659-71; Meltzer M, Cox N, Fukuda K. Modeling the Economic Impact of Pandemic Influenza in the United States: Implications for Setting Priorities for Intervention. Background paper. Atlanta, GA: CDC, 1999. Available at: http://www.cdc.gov/ncidod/eid/vol5no5/melt_back.htm (7 January 2011, date last accessed))]. The strong version of the Precautionary Principle would suggest using this prediction for vaccination campaigns. On the contrary, the non-extensive maximum entropy principle predicts a lower attack rate, which induces a 20% saving in public funding for vaccines doses. The need for an effective influenza pandemic prevention program, coupled with an efficient use of public

  13. Human rotavirus vaccine is highly efficacious when coadministered with routine expanded program of immunization vaccines including oral poliovirus vaccine in Latin America.

    Science.gov (United States)

    Tregnaghi, Miguel W; Abate, Héctor J; Valencia, Alejandra; Lopez, Pio; Da Silveira, Themis Reverbel; Rivera, Luis; Rivera Medina, Doris Maribel; Saez-Llorens, Xavier; Gonzalez Ayala, Silvia Elena; De León, Tirza; Van Doorn, Leen-Jan; Pilar Rubio, Maria Del; Suryakiran, Pemmaraju Venkata; Casellas, Javier M; Ortega-Barria, Eduardo; Smolenov, Igor V; Han, Htay-Htay

    2011-06-01

    The efficacy of a rotavirus vaccine against severe rotavirus gastroenteritis when coadministered with routine Expanded Program on Immunization (EPI) vaccines including oral polio vaccine (OPV) was evaluated in this study. Double-blind, randomized (2:1), placebo-controlled study conducted across 6 Latin American countries. Healthy infants (N = 6568) 6 to 12 weeks of age received 2 doses of RIX4414 vaccine or placebo following a 0, 1- to 2-month schedule. Routine vaccines including OPV were coadministered according to local EPI schedule. Vaccine efficacy (VE) against severe rotavirus gastroenteritis caused by circulating wild-type rotavirus from 2 weeks post-Dose 2 until 1 year of age was calculated with 95% confidence interval [CI]. Safety was assessed during the entire study period. Immunogenicity of RIX4414 and OPV was also assessed. During the efficacy follow-up period (mean duration = 7.4 months), 7 and 19 cases of severe rotavirus gastroenteritis were reported in the vaccine and placebo groups, respectively, with a VE of 81.6% (95% CI: 54.4-93.5). VE against severe rotavirus gastroenteritis caused by G1 type was 100% (95% CI: rotavirus types, respectively. There was no difference (P = 0.514) in the incidence of serious adverse events reported in the 2 groups. Antirotavirus IgA seropositivity rate at 1 to 2 months post-Dose 2 was 61.4% (95% CI: 53.7-68.6) in the RIX4414 group; similar seroprotection rates (≥96.0%) against the 3 antipoliovirus types was observed 1 month post-Dose 3 of OPV in both groups. RIX4414 was highly efficacious against severe rotavirus gastroenteritis caused by the circulating wild-type rotavirus (G1 and non-G1) when coadministered with routine EPI vaccines including OPV.

  14. Protective efficacy of an inactivated vaccine against H9N2 avian influenza virus in ducks.

    Science.gov (United States)

    Teng, Qiaoyang; Shen, Weixia; Liu, Qinfang; Rong, Guangyu; Chen, Lin; Li, Xuesong; Chen, Hongjun; Yang, Jianmei; Li, Zejun

    2015-09-17

    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.

  15. Safety and Efficacy Profile of Commercial Veterinary Vaccines against Rift Valley Fever: A Review Study

    Directory of Open Access Journals (Sweden)

    Moataz Alhaj

    2016-01-01

    Full Text Available Rift Valley Fever (RVF is an infectious illness with serious clinical manifestations and health consequences in humans as well as a wide range of domestic ruminants. This review provides significant information about the prevention options of RVF along with the safety-efficacy profile of commercial vaccines and some of RVF vaccination strategies. Information presented in this paper was obtained through a systematic investigation of published data about RVF vaccines. Like other viral diseases, the prevention of RVF relies heavily on immunization of susceptible herds with safe and cost-effective vaccine that is able to confer long-term protective immunity. Several strains of RVF vaccines have been developed and are available in commercial production including Formalin-Inactivated vaccine, live attenuated Smithburn vaccine, and the most recent Clone13. Although Formalin-Inactivated vaccine and live attenuated Smithburn vaccine are immunogenic and widely used in prevention programs, they proved to be accompanied by significant concerns. Despite Clone13 vaccine being suggested as safe in pregnant ewes and as highly immunogenic along with its potential for differentiating infected from vaccinated animals (DIVA, a recent study raised concerns about the safety of the vaccine during the first trimester of gestation. Accordingly, RVF vaccines that are currently available in the market to a significant extent do not fulfill the requirements of safety, potency, and DIVA. These adverse effects stressed the need for developing new vaccines with an excellent safety profile to bridge the gap in safety and immunity. Bringing RVF vaccine candidates to local markets besides the absence of validated serological test for DIVA remain the major challenges of RVF control.

  16. Dose response and efficacy of a live, attenuated human rotavirus vaccine in Mexican infants.

    Science.gov (United States)

    Ruiz-Palacios, Guillermo M; Guerrero, M Lourdes; Bautista-Márquez, Aurora; Ortega-Gallegos, Hilda; Tuz-Dzib, Fernando; Reyes-González, Leticia; Rosales-Pedraza, Gustavo; Martínez-López, Julia; Castañón-Acosta, Erika; Cervantes, Yolanda; Costa-Clemens, SueAnn; DeVos, Beatrice

    2007-08-01

    Immunization against rotavirus has been proposed as the most cost-effective intervention to reduce the disease burden associated with this infection worldwide. The objective of this study was to determine the dose response, immunogenicity, and efficacy of 2 doses of an oral, attenuated monovalent G1[P8] human rotavirus vaccine in children from the same setting in Mexico, where the natural protection against rotavirus infection was studied. From June 2001 through May 2003, 405 healthy infants were randomly assigned to 1 of 3 vaccine groups (virus concentrations 10(4.7), 10(5.2), and 10(5.8) infectious units) and to a placebo group and were monitored to the age of 2 years. The vaccine/placebo was administered concurrently with diphtheria-tetanus toxoid-pertussis/hepatitis B/Haemophilus influenzae type b vaccine at 2 and 4 months of age. After the administration of the first vaccine/placebo dose, weekly home visits to collect information regarding infant health were conducted. Stool samples were collected during each gastroenteritis episode and tested for rotavirus antigen and serotype. The vaccine was well tolerated and induced a greater rate of seroconversion than observed in infants who received placebo. For the pooled vaccine groups, efficacy after 2 oral doses was 80% and 95% against any and severe rotavirus gastroenteritis, respectively. Efficacy was 100% against severe rotavirus gastroenteritis and 70% against severe gastroenteritis of any cause with the vaccine at the highest virus concentration (10(5.8) infectious units). The predominant infecting rotavirus serotype in this cohort was wild-type G1 (85%). Adverse events, including fever, irritability, loss of appetite, cough, diarrhea, and vomiting, were similar among vaccinees and placebo recipients. This new oral, live, attenuated human rotavirus vaccine was safe, immunogenic, and highly efficacious in preventing any and, more importantly, severe rotavirus gastroenteritis in healthy infants. This vaccine

  17. Evaluation of the efficacy of an autogenous Escherichia coli vaccine in broiler breeders

    DEFF Research Database (Denmark)

    Li, Lili; Thøfner, Ida; Christensen, Jens Peter

    2017-01-01

    vaccine in broiler breeders. Three groups of 28 weeks old broiler breeders (unvaccinated, vaccinated once and twice, respectively) were challenged with a homologous E. coli strain (same strain as included in the vaccine) or a heterologous challenge strain in an experimental ascending model. The clinical...... infection, significant protection of an autogenous E. coli vaccine against neither a homologous nor a heterologous E. coli challenge could not be documented.......In poultry production Escherichia coli autogenous vaccines are often used. However, the efficacy of autogenous E. coli vaccinations has not been evaluated experimentally in chickens after start of lay. The aim of the present study was to evaluate the protective effect of an autogenous E. coli...

  18. Efficacy of single calfhood vaccination of elk with Brucella abortus strain 19

    Science.gov (United States)

    Roffe, T.J.; Jones, L.C.; Coffin, K.; Drew, M.L.; Sweeney, Steven J.; Hagius, S.D.; Elzer, P.H.; Davis, D.

    2004-01-01

    Brucellosis has been eradicated from cattle in the states of Wyoming, Montana, and Idaho, USA. However, free-ranging elk (Cervus elaphus) that use feedgrounds in the Greater Yellowstone Area (GYA) and bison (Bison bison) in Yellowstone and Grand Teton national parks still have high seroprevalence to the disease and have caused loss of brucellosis-free status in Wyoming. Management tools to control or eliminate the disease are limited; however, wildlife vaccination is among the methods currently used by wildlife managers in Wyoming. We conducted a controlled challenge study of single calfhood vaccination. Elk calves, caught in January and February of 1999 and 2000 and acclimated to captivity for 3 weeks, were randomly assigned to control or vaccinate groups. The vaccinate groups received Brucetta abortus vaccine strain 19 (S19) by hand-delivered intramuscular injection. Calves were raised to adulthood and bred at either 2.5 or 3.5 years of age for 2000 and 1999 captures, respectively. Eighty-nine (44 controls, 45 vaccinates) pregnant elk entered the challenge portion of the study. We challenged elk at mid-gestation with pathogenic B. abortus strain 2308 by intraconjunctival instillation. Abortion occurred in significantly more (P = 0.002) controls (42; 93%) than vaccinates (32; 71%), and vaccine protected 25% of the vaccinate group. We used Brucella culture of fetus/calf tissues to determine the efficacy of vaccination for preventing infection, and we found that the number of infected fetuses/calves did not differ between controls and vaccinates (P = 0.14). Based on these data, single calfhood vaccination with S19 has low efficacy, will likely have only little to moderate effect on Brucella prevalence in elk, and is unlikely to eradicate the disease in wildlife of the GYA.

  19. Efficacy of a therapeutic vaccine using mutated β-amyloid sensitized dendritic cells in Alzheimer's mice.

    Science.gov (United States)

    Luo, Zhongqiu; Li, Jialin; Nabar, Neel R; Lin, Xiaoyang; Bai, Ge; Cai, Jianfeng; Zhou, Shu-Feng; Cao, Chuanhai; Wang, Jinhuan

    2012-09-01

    Despite FDA suspension of Elan's AN-1792 amyloid beta (Aβ) vaccine in phase IIb clinical trials, the implications of this study are the guiding principles for contemporary anti-Aβ immunotherapy against Alzheimer's disease (AD). AN-1792 showed promising results with regards to Aβ clearance and cognitive function improvement, but also exhibited an increased risk of Th1 mediated meningoencephalitis. As such, vaccine development has continued with an emphasis on eliciting a notable anti-Aβ antibody titer, while avoiding the unwanted Th1 pro-inflammatory response. Previously, we published the first report of an Aβ sensitized dendritic cell vaccine as a therapeutic treatment for AD in BALB/c mice. Our vaccine elicited an anti-Aβ titer, with indications that a Th1 response was not present. This study is the first to investigate the efficacy and safety of our dendritic cell vaccine for the prevention of AD in transgenic mouse models (PDAPP) for AD. We also used Immunohistochemistry to characterize the involvement of LXR, ABCA1, and CD45 in order to gain insight into the potential mechanisms through which this vaccine may provide benefit. The results indicate that (1) the use of mutant Aβ1-42 sensitized dendritic cell vaccine results in durable antibody production, (2) the vaccine provides significant benefits with regards to cognitive function without the global (Th1) inflammation seen in prior Aβ vaccines, (3) histological studies showed an overall decrease in Aβ burden, with an increase in LXR, ABCA1, and CD45, and (4) the beneficial results of our DC vaccine may be due to the LXR/ABCA1 pathway. In the future, mutant Aβ sensitized dendritic cell vaccines could be an efficacious and safe method for the prevention or treatment of AD that circumvents problems associated with traditional anti-Aβ vaccines.

  20. Increased efficacy of immersion vaccination in fish with hyperosmotic pretreatment

    NARCIS (Netherlands)

    Huising, M.O.; Guichelaar, T.; Hoek, C.; Verburg-van Kemenade, B.M.L.; Flik, G.; Savelkoul, H.F.J.; Rombout, J.H.W.M.

    2003-01-01

    Immersion vaccination is common practice in aquaculture, because of its convenience for mass vaccination with sufficient protection. However, the mechanisms of antigen uptake and presentation, resulting in a protective immune response and the role of the innate immune system therein are largely

  1. Efficacy of an adjuvanted herpes zoster subunit vaccine in older adults.

    Science.gov (United States)

    Lal, Himal; Cunningham, Anthony L; Godeaux, Olivier; Chlibek, Roman; Diez-Domingo, Javier; Hwang, Shinn-Jang; Levin, Myron J; McElhaney, Janet E; Poder, Airi; Puig-Barberà, Joan; Vesikari, Timo; Watanabe, Daisuke; Weckx, Lily; Zahaf, Toufik; Heineman, Thomas C

    2015-05-28

    In previous phase 1-2 clinical trials involving older adults, a subunit vaccine containing varicella-zoster virus glycoprotein E and the AS01B adjuvant system (called HZ/su) had a clinically acceptable safety profile and elicited a robust immune response. We conducted a randomized, placebo-controlled, phase 3 study in 18 countries to evaluate the efficacy and safety of HZ/su in older adults (≥50 years of age), stratified according to age group (50 to 59, 60 to 69, and ≥70 years). Participants received two intramuscular doses of the vaccine or placebo 2 months apart. The primary objective was to assess the efficacy of the vaccine, as compared with placebo, in reducing the risk of herpes zoster in older adults. A total of 15,411 participants who could be evaluated received either the vaccine (7698 participants) or placebo (7713 participants). During a mean follow-up of 3.2 years, herpes zoster was confirmed in 6 participants in the vaccine group and in 210 participants in the placebo group (incidence rate, 0.3 vs. 9.1 per 1000 person-years) in the modified vaccinated cohort. Overall vaccine efficacy against herpes zoster was 97.2% (95% confidence interval [CI], 93.7 to 99.0; P<0.001). Vaccine efficacy was between 96.6% and 97.9% for all age groups. Solicited reports of injection-site and systemic reactions within 7 days after vaccination were more frequent in the vaccine group. There were solicited or unsolicited reports of grade 3 symptoms in 17.0% of vaccine recipients and 3.2% of placebo recipients. The proportions of participants who had serious adverse events or potential immune-mediated diseases or who died were similar in the two groups. The HZ/su vaccine significantly reduced the risk of herpes zoster in adults who were 50 years of age or older. Vaccine efficacy in adults who were 70 years of age or older was similar to that in the other two age groups. (Funded by GlaxoSmithKline Biologicals; ZOE-50 ClinicalTrials.gov number, NCT01165177.).

  2. Efficacy, Safety, and Interactions of a Live Infectious Bursal Disease Virus Vaccine for Chickens Based on Strain IBD V877.

    Science.gov (United States)

    Geerligs, Harm J; Ons, Ellen; Boelm, Gert Jan; Vancraeynest, Dieter

    2015-03-01

    Infectious bursal disease (IBD) is a highly contagious disease in young chickens which can result in high morbidity and mortality and also in great economic losses. The main target for the virus is the lymphoid tissue with a special predilection for the bursa of Fabricius. Several vaccines are available to control the disease. Intermediate plus vaccines are used in chickens with high maternal antibody titers which face high infection pressure. An example of an intermediate plus vaccine is a live vaccine based on IBD strain V877. The results of an efficacy study in commercial broilers with different levels of maternally derived antibodies (MDA) showed that the V877-based IBD vaccine can break through maternal antibody titers of higher than 1100 as determined by an IBD ELISA. The safety of the vaccine was demonstrated in a study in which specific-pathogen-free (SPF) chickens were vaccinated with a tenfold dose of the vaccine strain and a tenfold dose of the vaccine strain after five back passages in SPF chickens. The vaccine virus caused lesions, as could be expected for an intermediate plus vaccine, but the scores were not much higher than the maximal scores allowed for mild IBD vaccines in the European Pharmacopoeia, and reversion to virulence was absent. In studies in SPF chickens, there were no negative impacts by the IBD V877 vaccine on the efficacy of a live QX-like IB vaccine and a live Newcastle disease La Sota vaccine in vaccination challenge studies, although the IBD vaccine had a negative effect on the antibody response generated by the QX-like IB vaccine. It is concluded that the IBD V877 vaccine has the capacity to break through high levels of MDA, has a satisfactory safety profile, and interactions with other live vaccines are limited. In order to limit bursal lesions after vaccination it is recommended to confirm the presence of MDA before vaccinating with the V877 vaccine.

  3. Short-term safety and efficacy of the biodegradable iron stent in mini-swine coronary arteries

    Institute of Scientific and Technical Information of China (English)

    WU Chao; QIU Hong; HU Xiao-ying; RUAN Ying-mao; TIAN Yi; CHU Yan; XU Xin-lin

    2013-01-01

    Background To overcome the drawbacks of permanent stents,biodegradable stents have been studied in recent years.The bioabsorbable polymer vascular scaffold (BVS) was the first bioabsorbable stent to undergo clinical trials,demonstrating safety and feasibility in the ABSORB studies.Iron can potentially serve as the biomaterial for biodegradable stents.This study aimed to assess the short-term safety and efficacy of a biodegradable iron stent in mini-swine coronary arteries.Methods Eight iron stents and eight cobalt chromium alloy (VISION) control stents were randomly implanted into the LAD and RCA of eight healthy mini-swine,respectively.Two stents of the same metal base were implanted into one animal.At 28 days the animals were sacrificed after coronary angiography,and histopathological examinations were performed.Results Histomorphometric measurements showed that mean neointimal thickness ((0.46±0.17) mm vs.(0.45±0.18)mm,P=0.878),neointimal area ((2.55±0.91) mm2 vs.(3.04±1.15) mm2,P=0.360) and percentage of area stenosis ((44.50±11.40)% vs.(46.00±17.95)%,P=0.845) were not significantly different between the iron stents and VISION stents.There was no inflammation,thrombosis or necrosis in either group.The scanning electron microscopy (SEM) intimal injury scores (0.75±1.04 vs.0.88±0.99,P=0.809) and number of proliferating cell nuclear antigen (PCNA) positive staining cells were not significantly different between the two groups.The percentage of neointimal coverage by SEM examination was numerically higher in iron stents than in VISION stents ((84.38±14.50)% vs.(65.00±22.04)%,P=0.057),but the difference was not statistically significant.Iron staining in the tissue surrounding the iron stents at 28 days was positive and the vascular wall adjacent to the iron stent had a brownish tinge,consistent with iron degradation.No abnormal histopathological changes were detected in coronary arteries or major organs.Conclusions The biodegradable iron stent has

  4. CAF01 potentiates immune responses and efficacy of an inactivated influenza vaccine in ferrets.

    Directory of Open Access Journals (Sweden)

    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.

  5. Efficacy of a dexamethasone-eluting nitinol stent on the inhibition of pseudointimal hyperplasia in a transjugular intrahepatic portosystemic shunt: an experimental study in a swine model

    Energy Technology Data Exchange (ETDEWEB)

    Seo, Tae Seok [Korea University Guro Hospital, Seoul (Korea, Republic of); Oh, Joo Hyeogn; Park, Young Koo [Kyung Hee University Hospital, Seoul (Korea, Republic of); Song, Ho Young [University of Ulsan, College of Medicine, Seoul (Korea, Republic of); Park, Sang Joon [Hallym University, College of Medicine, Seoul (Korea, Republic of); Yuk, Sun Hong [Hannam University, Daejeon (Korea, Republic of)

    2005-12-15

    We wanted to evaluate the feasibility and efficacy of using a dexamethasone (DM)-eluting nitinol stent to inhibit the pseudointimal hyperplasia following stent placement in the transjugular intrahepatic portosystemic shunt tract (TIPS) of a swine. Fifteen stents were constructed using 0.15 mm-thick nitinol wire; they were 60 mm in length and 10 mm in diameter. The metallic stents were then classified into three types; type 1 and 2 was coated with the mixture of 12% and 20%, respectively, of DM solution and polyurethane (PU), while type 3 was a bare stent that was used for control study. In fifteen swine, each type of stent was implanted in the TIPS tract of 5 swine, and each animal was sacrificed 2 weeks after TIPS creation. The proliferation of the pseudointima was evaluated both on follow-up portogram and pathologic examination. One TIPS case, using the type 1 stent, and two TIPS cases, using the type 2 stent, maintained their luminal patency while the others were all occluded. On the histopathologic analysis, the mean of the maximum pseudointimal hyperplasia was expressed as the percentage of the stent radius that was patent, and these values were 51.2%, 50% and 76% for the type 1, 2, and 3 stents, respectively. The DM-eluting stent showed a tendency to reduce the development of pseudointimal hyperplasia in the TIPS tract of a swine model with induced-portal hypertension.

  6. Development of a swine specific 9-plex Luminex cytokine assay and assessment of immunity after porcine reproductive and respiratory syndrome virus (PRRSV) vaccination: Elevated serum IL-12 levels are not predictive of protect

    Science.gov (United States)

    A Luminex multiplex swine cytokine assay was developed to measure 9 cytokines simultaneously in pig serum and tested in a porcine reproductive and respiratory syndrome virus (PRRSV) vaccine/challenge study. This assay detects innate (IL-1ß, IL-6, IL-8, IFNa, TNFa); regulatory (IL-10), Th1 (IL-12, I...

  7. Development of a rotavirus vaccine: clinical safety, immunogenicity, and efficacy of the pentavalent rotavirus vaccine, RotaTeq.

    Science.gov (United States)

    Ciarlet, Max; Schödel, Florian

    2009-12-30

    Initial approaches for rotavirus vaccines were based on the classical "Jennerian" approach and utilized simian and bovine rotavirus strains, which provided cross-protection against human rotavirus strains but did not cause illness in infants and young children because of their species-specific tropism. The demonstrated efficacy of these vaccines was not consistent across studies. Thus, human-animal reassortants containing an animal rotavirus backbone with human rotavirus surface G and/or P proteins were developed, which demonstrated more consistent efficacy than that observed with the non-reassortant rotavirus strains. The pentavalent rotavirus vaccine, RotaTeq, contains 5 human-bovine reassortant rotaviruses consisting of a bovine (WC3) backbone with human rotavirus surface proteins representative of the most common G (G1, G2, G3, G4) or P (P1A[8]) types worldwide. The present review focuses on the development of the pentavalent rotavirus vaccine RotaTeq. Results of a large-scale Phase III clinical study showed that three doses of RotaTeq were immunogenic, efficacious, and well tolerated with no increased clinical risk of intussusception. RotaTeq was efficacious against rotavirus gastroenteritis of any severity (74%) and severe disease (98-100%), using a validated clinical scoring system. Reductions in rotavirus-associated hospitalizations and emergency department (ED) visits, for up to 2 years post-vaccination, were 95% in Europe, 97% in the United States, and 90% in the Latin American/Caribbean regions. RotaTeq was recently shown to be up to 100% effective in routine use in the US in reducing hospitalizations and ED visits and 96% effective in reducing physician visits. Additional studies in 8 different locations in the US have shown 85-95% reduction in rotavirus-associated hospitalizations and/or ED visits in the first 2-2.5 years of routine use.

  8. Swine brucellosis: current perspectives

    Directory of Open Access Journals (Sweden)

    Olsen SC

    2016-12-01

    Full Text Available SC Olsen, FM Tatum Infectious Bacterial Diseases of Livestock Research Unit, National Animal Disease Center, Agricultural Research Service, United States Department of Agriculture, Ames, IA, USA Abstract: Brucella suis is a significant zoonotic species that is present in domestic livestock and wildlife in many countries worldwide. Transmission from animal reservoirs is the source of human infection as human-to-human transmission is very rare. Although swine brucellosis causes economic losses in domestic livestock, preventing human infection is the primary reason for its emphasis in disease control programs. Although disease prevalence varies worldwide, in areas outside of Europe, swine brucellosis is predominantly caused by B. suis biovars 1 and 3. In Europe, swine are predominantly infected with biovar 2 which is much less pathogenic in humans. In many areas worldwide, feral or wild populations of swine are important reservoir hosts. Like other Brucella spp. in their natural host, B. suis has developed mechanisms to survive in an intracellular environment and evade immune detection. Limitations in sensitivity and specificity of current diagnostics require use at a herd level, rather for individual animals. There is currently no commercial vaccine approved for preventing brucellosis in swine. Although not feasible in all situations, whole-herd depopulation is the most effective regulatory mechanism to control swine brucellosis. Keywords: livestock, transmission, pathogenicity, vaccine, host, infection

  9. Calculation of the efficacy of vaccines against tick infestations on cattle

    Directory of Open Access Journals (Sweden)

    Rodrigo Casquero Cunha

    Full Text Available Cattle ticks are responsible for great economic losses in cattle farming worldwide, and their main control method, chemicals, has been showing problems, whether resulting from the development of resistant strains of ticks or environmental contamination. Research studies directed toward developing vaccines against ticks are emerging. One way to evaluate those vaccines is to calculate the percentage of efficacy. The aim of this study was to analyze scientific publications archived in PubMed that used this method of assessment and discuss the main factors that may affect its calculation. Thus, 25 articles addressing this subject were selected. The percentage of efficacy was usually calculated in one of two ways, with one considering the reduced fertility of eggs and the other not. The latter method may underestimate the vaccine efficacy, and the most complete formula for calculating the efficacy reflects how much the vaccine actually affects the infestation. In our view, the use of the complete formula for calculating the percentage of efficacy is broader and more representative of the vaccine effect on the tick population.

  10. Efficacy of a Low-Cost, Heat-Stable Oral Rotavirus Vaccine in Niger.

    Science.gov (United States)

    Isanaka, Sheila; Guindo, Ousmane; Langendorf, Celine; Matar Seck, Amadou; Plikaytis, Brian D; Sayinzoga-Makombe, Nathan; McNeal, Monica M; Meyer, Nicole; Adehossi, Eric; Djibo, Ali; Jochum, Bruno; Grais, Rebecca F

    2017-03-23

    Each year, rotavirus gastroenteritis is responsible for about 37% of deaths from diarrhea among children younger than 5 years of age worldwide, with a disproportionate effect in sub-Saharan Africa. We conducted a randomized, placebo-controlled trial in Niger to evaluate the efficacy of a live, oral bovine rotavirus pentavalent vaccine (BRV-PV, Serum Institute of India) to prevent severe rotavirus gastroenteritis. Healthy infants received three doses of the vaccine or placebo at 6, 10, and 14 weeks of age. Episodes of gastroenteritis were assessed through active and passive surveillance and were graded on the basis of the score on the Vesikari scale (which ranges from 0 to 20, with higher scores indicating more severe disease). The primary end point was the efficacy of three doses of vaccine as compared with placebo against a first episode of laboratory-confirmed severe rotavirus gastroenteritis (Vesikari score, ≥11) beginning 28 days after dose 3. Among the 3508 infants who were included in the per-protocol efficacy analysis, there were 31 cases of severe rotavirus gastroenteritis in the vaccine group and 87 cases in the placebo group (2.14 and 6.44 cases per 100 person-years, respectively), for a vaccine efficacy of 66.7% (95% confidence interval [CI], 49.9 to 77.9). Similar efficacy was seen in the intention-to-treat analyses, which showed a vaccine efficacy of 69.1% (95% CI, 55.0 to 78.7). There was no significant between-group difference in the risk of adverse events, which were reported in 68.7% of the infants in the vaccine group and in 67.2% of those in the placebo group, or in the risk of serious adverse events (in 8.3% in the vaccine group and in 9.1% in the placebo group); there were 27 deaths in the vaccine group and 22 in the placebo group. None of the infants had confirmed intussusception. Three doses of BRV-PV, an oral rotavirus vaccine, had an efficacy of 66.7% against severe rotavirus gastroenteritis among infants in Niger. (Funded by M

  11. A New Furunculosis Challenge Method for Evaluation of Vaccine Efficacy in Rainbow Trout

    DEFF Research Database (Denmark)

    Marana, Moonika Haahr; Chettri, Jiwan Kumar; Skov, Jakob

    2016-01-01

    Experimental infection of fish for vaccine efficacy studies is associated with several limitations. Administration of live bacteria with the purpose of causing disease in fish can be performed by co-habitation, immersion or injection. We have developed a new Aeromonas salmonicida challenge method...... for rainbow trout and have applied it for evaluation of furunculosis vaccine efficacy. The method reveals development of systemic immunity in fish as live bacteria are introduced in the tail fin epidermis distant from the vaccine injection site (peritoneal cavity). This method seeks to mimic natural infection...... in fish farms where tail biting and therefore bacterial expo- sure to tail fin ulcers is widespread. By use of a multi-needle device ten epidermal perforations were introduced in the dorsal part of the tail fin of anaesthetized rainbow trout (vaccinated or naive). Subsequently 100 μL (3.4 × 108 colony-forming...

  12. Efficacy of a vaccine formula against tuberculosis in cattle.

    Directory of Open Access Journals (Sweden)

    Germinal J Canto Alarcon

    Full Text Available "Test-and-slaughter" has been successful in industrialized countries to control and eradicate tuberculosis from cattle; however, this strategy is too expensive for developing nations, where the prevalence is especially high. Vaccination with the Calmette-Guérin (BCG strain has been shown to protect against the development of lesions in vaccinated animals: mouse, cattle and wildlife species. In this study, the immune response and the pathology of vaccinated (BCG-prime and BCG prime-CFP-boosted and unvaccinated (controls calves were evaluated under experimental settings. A 10(6 CFU dose of the BCG strain was inoculated subcutaneously on the neck to two groups of ten animas each. Thirty days after vaccination, one of the vaccinated groups was boosted with an M. bovis culture filtrate protein (CFP. Three months after vaccination, the three groups of animals were challenged with 5×10(5 CFU via intranasal by aerosol with a field strain of M. bovis. The immune response was monitored throughout the study. Protection was assessed based on immune response (IFN-g release prechallenge, presence of visible lesions in lymph nodes and lungs at slaughter, and presence of bacilli in lymph nodes and lung samples in histological analysis. Vaccinated cattle, either with the BCG alone or with BCG and boosted with CFP showed higher IFN-g response, fewer lesions, and fewer bacilli per lesion than unvaccinated controls after challenge. Animals with low levels of IFN-g postvaccine-prechallenge showed more lesions than animals with high levels. Results from this study support the argument that vaccination could be incorporated into control programs to reduce the incidence of TB in cattle in countries with high prevalence.

  13. Immunogenicity and in vitro Protective Efficacy of a Recombinant Multistage Plasmodium falciparum Candidate Vaccine

    Science.gov (United States)

    Shi, Ya Ping; Hasnain, Seyed E.; Sacci, John B.; Holloway, Brian P.; Fujioka, Hisashi; Kumar, Nirbhay; Wohlhueter, Robert; Hoffman, Stephen L.; Collins, William E.; Lal, Altaf A.

    1999-02-01

    Compared with a single-stage antigen-based vaccine, a multistage and multivalent Plasmodium falciparum vaccine would be more efficacious by inducing "multiple layers" of immunity. We have constructed a synthetic gene that encodes for 12 B cell, 6 T cell proliferative, and 3 cytotoxic T lymphocyte epitopes derived from 9 stage-specific P. falciparum antigens corresponding to the sporozoite, liver, erythrocytic asexual, and sexual stages. The gene was expressed in the baculovirus system, and a 41-kDa antigen, termed CDC/NIIMALVAC-1, was purified. Immunization in rabbits with the purified protein in the presence of different adjuvants generated antibody responses that recognized vaccine antigen, linear peptides contained in the vaccine, and all stages of P. falciparum. In vitro assays of protection revealed that the vaccine-elicited antibodies strongly inhibited sporozoite invasion of hepatoma cells and growth of blood-stage parasites in the presence of monocytes. These observations demonstrate that a multicomponent, multistage malaria vaccine can induce immune responses that inhibit parasite development at multiple stages. The rationale and approach used in the development of a multicomponent P. falciparum vaccine will be useful in the development of a multispecies human malaria vaccine and vaccines against other infectious diseases.

  14. Ontology-supported research on vaccine efficacy, safety and integrative biological networks.

    Science.gov (United States)

    He, Yongqun

    2014-07-01

    While vaccine efficacy and safety research has dramatically progressed with the methods of in silico prediction and data mining, many challenges still exist. A formal ontology is a human- and computer-interpretable set of terms and relations that represent entities in a specific domain and how these terms relate to each other. Several community-based ontologies (including Vaccine Ontology, Ontology of Adverse Events and Ontology of Vaccine Adverse Events) have been developed to support vaccine and adverse event representation, classification, data integration, literature mining of host-vaccine interaction networks, and analysis of vaccine adverse events. The author further proposes minimal vaccine information standards and their ontology representations, ontology-based linked open vaccine data and meta-analysis, an integrative One Network ('OneNet') Theory of Life, and ontology-based approaches to study and apply the OneNet theory. In the Big Data era, these proposed strategies provide a novel framework for advanced data integration and analysis of fundamental biological networks including vaccine immune mechanisms.

  15. Development of an Aotus nancymaae Model for Shigella Vaccine Immunogenicity and Efficacy Studies

    OpenAIRE

    Gregory, Michael; Kaminski, Robert W.; Lugo-Roman, Luis A.; Galvez Carrillo, Hugo; Tilley, Drake Hamilton; Baldeviano, Christian; Simons, Mark P.; Reynolds, Nathanael D.; Ranallo, Ryan T.; Suvarnapunya, Akamol E.; Venkatesan, Malabi M.; Oaks, Edwin V.

    2014-01-01

    Several animal models exist to evaluate the immunogenicity and protective efficacy of candidate Shigella vaccines. The two most widely used nonprimate models for vaccine development include a murine pulmonary challenge model and a guinea pig keratoconjunctivitis model. Nonhuman primate models exhibit clinical features and gross and microscopic colonic lesions that mimic those induced in human shigellosis. Challenge models for enterotoxigenic Escherichia coli (ETEC) and Campylobacter spp. have...

  16. Protein energy malnutrition alters mucosal IgA responses and reduces mucosal vaccine efficacy in mice.

    Science.gov (United States)

    Rho, Semi; Kim, Heejoo; Shim, Seung Hyun; Lee, Seung Young; Kim, Min Jung; Yang, Bo-Gie; Jang, Myoung Ho; Han, Byung Woo; Song, Man Ki; Czerkinsky, Cecil; Kim, Jae-Ouk

    2017-10-01

    Oral vaccine responsiveness is often lower in children from less developed countries. Childhood malnutrition may be associated with poor immune response to oral vaccines. The present study was designed to investigate whether protein energy malnutrition (PEM) impairs B cell immunity and ultimately reduces oral vaccine efficacy in a mouse model. Purified isocaloric diets containing low protein (1/10 the protein of the control diet) were used to determine the effect of PEM. PEM increased both nonspecific total IgA and oral antigen-specific IgA in serum without alteration of gut permeability. However, PEM decreased oral antigen-specific IgA in feces, which is consistent with decreased expression of polymeric Immunoglobulin receptor (pIgR) in the small intestine. Of note, polymeric IgA was predominant in serum under PEM. In addition, PEM altered B cell development status in the bone marrow and increased the frequency of IgA-secreting B cells, as well as IgA secretion by long-lived plasma cells in the small intestinal lamina propria. Moreover, PEM reduced the protective efficacy of the mucosally administered cholera vaccine and recombinant attenuated Salmonella enterica serovar Typhimurium vaccine in a mouse model. Our results suggest that PEM can impair mucosal immunity where IgA plays an important role in host protection and may partly explain the reduced efficacy of oral vaccines in malnourished subjects. Copyright © 2017 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

  17. Cardiopulmonary Resuscitation in Microgravity: Efficacy in the Swine During Parabolic Flight

    Science.gov (United States)

    Johnston, Smith L.; Campbell, Mark R.; Billica, Roger D.; Gilmore, Stevan M.

    2004-01-01

    INTRODUCTION: The International Space Station will need to be as capable as possible in providing Advanced Cardiac Life Support (ACLS) and cardiopulmonary resuscitation (CPR). Previous studies with manikins in parabolic microgravity (0 G) have shown that delivering CPR in microgravity is difficult. End tidal carbon dioxide (PetCO2) has been previously shown to be an effective non-invasive tool for estimating cardiac output during cardiopulmonary resuscitation. Animal models have shown that this diagnostic adjunct can be used as a predictor of survival when PetCO2 values are maintained above 25% of pre-arrest values. METHODS: Eleven anesthetized Yorkshire swine were flown in microgravity during parabolic flight. Physiologic parameters, including PetCO2, were monitored. Standard ACLS protocols were used to resuscitate these models after chemical induction of cardiac arrest. Chest compressions were administered using conventional body positioning with waist restraint and unconventional vertical-inverted body positioning. RESULTS: PetCO2 values were maintained above 25% of both 1-G and O-G pre-arrest values in the microgravity environment (33% +/- 3 and 41 +/- 3). No significant difference between 1-G CPR and O-G CPR was found in these animal models. Effective CPR was delivered in both body positions although conventional body positioning was found to be quickly fatiguing as compared with the vertical-inverted. CONCLUSIONS: Cardiopulmonary resuscitation can be effectively administered in microgravity (0 G). Validation of this model has demonstrated that PetCO2 levels were maintained above a level previously reported to be predictive of survival. The unconventional vertical-inverted position provided effective CPR and was less fatiguing as compared with the conventional body position with waist restraints.

  18. Efficacy and safety of a combined Porcine Circovirus and Mycoplasma hyopneumoniae vaccine in finishing pigs

    Directory of Open Access Journals (Sweden)

    Maarten Witvliet

    2015-01-01

    Full Text Available The safety and protective efficacy of a new one dose combination vaccine containing Porcine Circovirus type 2 (PCV2 and M. hyopneumoniae antigens – Porcilis® PCV M Hyo - was evaluated in laboratory studies and under field conditions. Vaccination resulted in a moderate temperature increase on the day of vaccination and mild systemic and local reactions were found in only a low percentage of the vaccinated pigs. The local reactions observed were small (max. 2 cm and transient (max. 1 day. In short term (onset of immunity and long term (duration of immunity challenge studies with the individual pathogens, the vaccine significantly reduced the PCV2 load in lymphoid tissue and lungs and M. hyopneumoniae-induced lung lesions. In a placebo-controlled field trial on a farm where both PCV2 and M. hyopneumoniae were present, vaccination of piglets at 3 weeks of age resulted in a reduction of PCV2 viremia and shedding and lower lung lesion scores at slaughter. In addition, a positive effect on the average daily weight gain (+ 34 g/day in the finishing phase was observed. It can therefore be concluded that this new ready to use combination vaccine is safe and efficacious against PCV2 and M. hyopneumoniae single and combined infections.

  19. Efficacy of dart or booster vaccination with strain RB51 in protecting bison against experimental Brucella abortus challenge

    Science.gov (United States)

    Vaccination is an effective tool for reducing the prevalence of brucellosis in natural hosts. In this study, we characterized the efficacy of the Brucella abortus strain RB51 (RB51) vaccine in bison when delivered by single intramuscular vaccination (Hand RB51), single pneumatic dart delivery (Dart ...

  20. Efficacy of RTS,S/AS01E vaccine against malaria in children 5 to 17 months of age

    DEFF Research Database (Denmark)

    Bejon, Philip; Lusingu, John; Olotu, Ally

    2008-01-01

    . We evaluated the efficacy of RTS,S given with a more immunogenic adjuvant system (AS01E) in children 5 to 17 months of age, a target population for vaccine licensure. METHODS: We conducted a double-blind, randomized trial of RTS,S/AS01E vaccine as compared with rabies vaccine in children in Kilifi...... vaccine or the control (rabies) vaccine. Among the 809 children who completed the study procedures according to the protocol, the cumulative number in whom clinical malaria developed was 32 of 402 assigned to receive RTS,S/AS01E and 66 of 407 assigned to receive the rabies vaccine; the adjusted efficacy...... rate for RTS,S/AS01E was 53% (95% confidence interval [CI], 28 to 69; Prabies vaccine, with an adjusted rate of efficacy...

  1. Recombinant rabies virus expressing dog GM-CSF is an efficacious oral rabies vaccine for dogs.

    Science.gov (United States)

    Zhou, Ming; Wang, Lei; Zhou, Songqin; Wang, Zhao; Ruan, Juncheng; Tang, Lijun; Jia, Ziming; Cui, Min; Zhao, Ling; Fu, Zhen F

    2015-11-17

    Developing efficacious oral rabies vaccines is an important step to increase immunization coverage for stray dogs, which are not accessible for parenteral vaccination. Our previous studies have demonstrated that recombinant rabies virus (RABV) expressing cytokines/chemokines induces robust protective immune responses after oral immunization in mice by recruiting and activating dendritic cells (DCs) and B cells. To develop an effective oral rabies vaccine for dogs, a recombinant attenuated RABV expressing dog GM-CSF, designated as LBNSE-dGM-CSF was constructed and used for oral vaccination in a dog model. Significantly more DCs or B cells were activated in the peripheral blood of dogs vaccinated orally with LBNSE-dGM-CSF than those vaccinated with the parent virus LBNSE, particularly at 3 days post immunization (dpi). As a result, significantly higher levels of virus neutralizing antibodies (VNAs) were detected in dogs immunized with LBNSE-dGM-CSF than with the parent virus. All the immunized dogs were protected against a lethal challenge with 4500 MICLD50 of wild-type RABV SXTYD01. LBNSE-dGM-CSF was found to replicate mainly in the tonsils after oral vaccination as detected by nested RT-PCR and immunohistochemistry. Taken together, our results indicate that LBNSE-dGM-CSF could be a promising oral rabies vaccine candidate for dogs.

  2. Comprehensive sieve analysis of breakthrough HIV-1 sequences in the RV144 vaccine efficacy trial.

    Science.gov (United States)

    Edlefsen, Paul T; Rolland, Morgane; Hertz, Tomer; Tovanabutra, Sodsai; Gartland, Andrew J; deCamp, Allan C; Magaret, Craig A; Ahmed, Hasan; Gottardo, Raphael; Juraska, Michal; McCoy, Connor; Larsen, Brendan B; Sanders-Buell, Eric; Carrico, Chris; Menis, Sergey; Kijak, Gustavo H; Bose, Meera; Arroyo, Miguel A; O'Connell, Robert J; Nitayaphan, Sorachai; Pitisuttithum, Punnee; Kaewkungwal, Jaranit; Rerks-Ngarm, Supachai; Robb, Merlin L; Kirys, Tatsiana; Georgiev, Ivelin S; Kwong, Peter D; Scheffler, Konrad; Pond, Sergei L Kosakovsky; Carlson, Jonathan M; Michael, Nelson L; Schief, William R; Mullins, James I; Kim, Jerome H; Gilbert, Peter B

    2015-02-01

    The RV144 clinical trial showed the partial efficacy of a vaccine regimen with an estimated vaccine efficacy (VE) of 31% for protecting low-risk Thai volunteers against acquisition of HIV-1. The impact of vaccine-induced immune responses can be investigated through sieve analysis of HIV-1 breakthrough infections (infected vaccine and placebo recipients). A V1/V2-targeted comparison of the genomes of HIV-1 breakthrough viruses identified two V2 amino acid sites that differed between the vaccine and placebo groups. Here we extended the V1/V2 analysis to the entire HIV-1 genome using an array of methods based on individual sites, k-mers and genes/proteins. We identified 56 amino acid sites or "signatures" and 119 k-mers that differed between the vaccine and placebo groups. Of those, 19 sites and 38 k-mers were located in the regions comprising the RV144 vaccine (Env-gp120, Gag, and Pro). The nine signature sites in Env-gp120 were significantly enriched for known antibody-associated sites (p = 0.0021). In particular, site 317 in the third variable loop (V3) overlapped with a hotspot of antibody recognition, and sites 369 and 424 were linked to CD4 binding site neutralization. The identified signature sites significantly covaried with other sites across the genome (mean = 32.1) more than did non-signature sites (mean = 0.9) (p analysis of the breakthrough infections in the RV144 trial, this work describes a set of statistical methods and tools applicable to analysis of breakthrough infection genomes in general vaccine efficacy trials for diverse pathogens.

  3. Field study on the safety and efficacy of intradermal versus intramuscular vaccination against Mycoplasma hyopneumoniae.

    Science.gov (United States)

    Beffort, Lisa; Weiß, Christine; Fiebig, Kerstin; Jolie, Rika; Ritzmann, Mathias; Eddicks, Matthias

    2017-09-30

    The present study compares the safety and efficacy of a needle-free, intradermal Mycoplasma hyopneumoniae vaccine to an intramuscular one. 420 piglets (21+3 days of age) were randomly assigned to two vaccination groups (intradermal vaccination V1 (n=138), intramuscular vaccination V2 (n=144)) and one unvaccinated control group (CG, n=138). As safety parameters clinical observations, local injection site reactions (ISR) and rectal temperatures were assessed. Average daily weight gain (ADWG) and pneumonic lung lesions (LL) were measured as efficacy parameters. ISRs were minor in V1. After both vaccinations, no adverse impact on appetite was observed and mean rectal temperatures remained within physiological range. ADWG during the fattening period was significantly higher in vaccinated groups (V1: 913.4 g, V2: 924.5 g) compared with CG (875.6 g). No differences in ADWG were observed between V1 and V2. Vaccinated pigs had a significantly reduced mean extent of LL compared with CG. V1 was superior in reducing the extent and prevalence of LL compared with V2. These results reveal that a needle-free intradermal vaccination is safe and efficacious in reducing both the prevalence and extent of lung lesions, as well as in improving performance parameters, in a farrow-to-finish farm with a late onset of M hyopneumonia e infection. © British Veterinary Association (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  4. Emergency vaccination for classical swine fever will not be cost-effective for countries with a large export

    DEFF Research Database (Denmark)

    Boklund, Anette; Toft, Nils; Alban, Lis

    2009-01-01

    the epidemiological and economic consequences of such control strategies under Danish conditions with respect to herd demographics and geography as well as to investigate the effect of extra biosecurity on farms. We used InterSpread Plus to model the effect of nine different control strategies: the minimum measures......,H.M., Smak,J.A., Pluimers,F.H., 1999. The classical swine fever epidemic 1997-1998 in The Netherlands: descriptive epidemiology, Prev.Vet.Med., 42, 157-184. Fritzemeier,J., Teuffert,J., Greiser,Wilke,I, Staubach,Ch, Schlüter,H., Moennig,V., 2000. Epidemiology of classical swine fever in Germany in the 1990s......, Vet.Microbiol. 77, 29-41. MacKinnon, J.D., 2001. Some clinical and epidemiological aspects of the outbreak of Classical Swine Fe-ver in East Anglia in 2000, State Vet.J,, 11, 2-7....

  5. How to survey classical swine fever in wild boar (Sus scrofa) after the completion of oral vaccination? Chasing away the ghost of infection at different spatial scales.

    Science.gov (United States)

    Saubusse, Thibault; Masson, Jean-Daniel; Le Dimma, Mireille; Abrial, David; Marcé, Clara; Martin-Schaller, Regine; Dupire, Anne; Le Potier, Marie-Frédérique; Rossi, Sophie

    2016-01-25

    Oral mass vaccination (OMV) is considered as an efficient strategy for controlling classical swine fever (CSF) in wild boar. After the completion of vaccination, the presence of antibodies in 6-12 month-old hunted wild boars was expected to reflect a recent CSF circulation. Nevertheless, antibodies could also correspond to the long-lasting of maternal antibodies. This paper relates an experience of surveillance which lasted 4 years after the completion of OMV in a formerly vaccinated area, in north-eastern France (2010-2014). First, we conducted a retrospective analysis of the serological data collected in 6-12 month-old hunted wild boars from 2010 up to 2013, using a spatial Bayesian model accounting for hunting data autocorrelation and heterogeneity. At the level of the whole area, seroprevalence in juvenile boars decreased from 28% in 2010-2011 down to 1% in 2012-2013, but remained locally high (above 5%). The model revealed the existence of one particular seroprevalence hot-spot where a longitudinal survey of marked animals was conducted in 2013-2014, for deciphering the origin of antibodies. Eleven out of 107 captured piglets were seropositive when 3-4 months-old, but their antibody titres progressively decreased until 6-7 months of age. These results suggest piglets were carrying maternal antibodies, few of them carrying maternal antibodies lasting until the hunting season. Our study shows that OMV may generate confusion in the CSF surveillance several years after the completion of vaccination. We recommend using quantitative serological tools, hunting data modelling and capture approaches for better interpreting serological results after vaccination completion. Surveillance perspectives are further discussed.

  6. Interferon alpha inhibits replication of a live-attenuated porcine reproductive and respiratory syndrome virus vaccine preventing development of an adaptive immune response in swine.

    Science.gov (United States)

    Brockmeier, Susan L; Loving, Crystal L; Eberle, Kirsten C; Hau, Samantha J; Buckley, Alexandra; Van Geelen, Albert; Montiel, Nestor A; Nicholson, Tracy; Lager, Kelly M

    2017-12-01

    Type I interferons, such as interferon alpha (IFN-α), contribute to innate antiviral immunity by promoting production of antiviral mediators and are also involved in promoting an adaptive immune response. Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most devastating and costly viruses to the swine industry world-wide and has been shown to induce a meager IFN-α response. Previously we administered porcine IFN-α using a replication-defective adenovirus vector (Ad5-IFN-α) at the time of challenge with virulent PRRSV and demonstrated an increase in the number of virus-specific IFNγ secreting cells, indicating that the presence of IFN-α at the time of infection can alter the adaptive immune responses to PRRSV. In the current experiment, we explored the use of IFN-α as an adjuvant administered with live-attenuated PRRSV vaccine as a method to enhance immune response to the vaccine. Unlike the previous studies with fully virulent virus, one injection of the Ad5-IFN-α abolished replication of the vaccine virus and as a result there was no detectible adaptive immune response. Although IFN-α did not have the desired adjuvant effect, the results further highlight the use of IFN-α as a treatment for PRRSV infection. Published by Elsevier B.V.

  7. Efficacy of Killed Adjuvanted FMD Vaccine Developed with ...

    African Journals Online (AJOL)

    In this study the potency of killed Foot and Mouth Disease (FMD) vaccines serotypes SAT1 (Nig 1/98) and SAT 2 (Nig 2/97) virus isolates, formulated with montanide ISA 206 adjuvant was determined in guinea pigs and cattle by antibody assay using Complement Fixation and Serum Neutralization tests. The antibody titres ...

  8. Parasitism affects vaccine efficacy against Streptococcus iniae in Nile tilapia

    Science.gov (United States)

    Tilapia culture worldwide is estimated to be US$ 5 billion and is important to domestic and global food security. Parasites and bacteria co-occur in both extensive and intensive production of tilapia. The effect of parasitism on vaccine performance in fish is little studied. The objective of this ...

  9. Efficacy of early Mycoplasma hyopneumoniae vaccination against mixed respiratory disease in older fattening pigs.

    Science.gov (United States)

    Del Pozo Sacristán, R; Sierens, A; Marchioro, S B; Vangroenweghe, F; Jourquin, J; Labarque, G; Haesebrouck, F; Maes, D

    2014-02-22

    The present field study investigated the efficacy of early Mycoplasma hyopneumoniae vaccination in a farrow-to-finish pig herd with respiratory disease late in the fattening period due to combined infections with M hyopneumoniae and viral pathogens. Five hundred and forty piglets were randomly divided into three groups of 180 piglets each: two groups were vaccinated (Stellamune Once) at either 7 (V1) or 21 days of age (V2), and a third group was left non-vaccinated (NV). The three treatment groups were housed in different pens within the same compartment during the nursery period, and were housed in different but identical compartments during the fattening period. The efficacy was evaluated using performance and pneumonia lesions. The average daily weight gain during the fattening period was 19 (V1) and 18 g/day (V2) higher in both vaccinated groups when compared with the NV group. However, the difference was not statistically significant (P>0.05). The prevalence of pneumonia was significantly lower in both vaccinated groups (V1: 71.5 and V2: 67.1 per cent) when compared with the NV group (80.2 per cent) (Ppneumonia lesions were significantly reduced and growth losses numerically (not statistically significant) decreased by both vaccination schedules.

  10. Meta-analysis on the efficacy of foot-and-mouth disease emergency vaccination

    DEFF Research Database (Denmark)

    Hisham Beshara Halasa, Tariq; Boklund, Anette; Cox, S.

    2012-01-01

    The objectives of this study were to provide a summary quantification of the efficacy of FMD emergency vaccination based on a systematic review and a meta-analysis of available literature, and to further discuss the suitability of this review and meta-analysis to summarize and further interpret...... of clinical signs including FMD lesions and fever, while the virological protection parameter was estimated based on the outcome of laboratory tests that were used to diagnose FMD infection. A meta-analysis relative risk was calculated per protection parameter. Results of the meta-analyses were examined using...... vaccine. Fortunately, no significant bias that would alter the conclusions was encountered in the analysis. Meta-analysis showed to be a useful tool to summarize literature results from a systematic review of the efficacy of foot and mouth disease emergency vaccination....

  11. Efficacy of one dose vaccination against experimental infection with two Mycoplasma hyopneumoniae strains.

    Science.gov (United States)

    Michiels, Annelies; Arsenakis, Ioannis; Boyen, Filip; Krejci, Roman; Haesebrouck, Freddy; Maes, Dominiek

    2017-08-29

    Mycoplasma hyopneumoniae (M. hyopneumoniae) is the primary agent of enzootic pneumonia in pigs. Pigs are often infected with different M. hyopneumoniae strains. This study assessed the efficacy of vaccination against experimental infection with two genetically different M. hyopneumoniae strains in weaned piglets. At 33 days of age (D0), 45 M. hyopneumoniae-free piglets were randomly assigned to three different groups: 1) negative control group (NCG; n = 5): not vaccinated, not infected, 2) positive control group (PCG; n = 20): not vaccinated, infected, and 3) vaccination group (VG; n = 20): single vaccination with an inactivated whole-cell M. hyopneumoniae vaccine (Hyogen®, Ceva) (D1), infected. The PCG and VG were endotracheally inoculated with 7 × 10 7 CCU in 7 ml of the highly virulent M. hyopneumoniae strain F7.2C (D24) and 7 × 10 7 CCU in 7 ml low virulent strain F1.12A (D25). A respiratory disease score (RDS) was assessed from D24 until D53. At D53 (euthanasia), macroscopic lung lesions (MLL) were scored, log copies of M. hyopneumoniae DNA (qPCR) and IL-1 and IL-6-concentrations (ELISA) on bronchoalveolar lavage fluid were determined. The RDS and MLL at euthanasia were respectively 0, 1.20 and 0.55 (P hyopneumoniae strain as the vaccinated pigs coughed significantly less, and showed significantly less lung lesions compared to the non-vaccinated challenged pigs: the vaccinated animals showed a 52.9% lower RDS and 91.0% lower MLL compared to the PCG. In the bronchoalveolar lavage fluid collected at the necropsy of the vaccinated pigs, a significantly lower amount of M. hyopneumoniae-DNA and a significantly lower IL-1 and IL-6 concentration was found compared to the pigs of the PCG.

  12. A Francisella tularensis live vaccine strain that improves stimulation of antigen-presenting cells does not enhance vaccine efficacy.

    Directory of Open Access Journals (Sweden)

    Deanna M Schmitt

    Full Text Available Vaccination is a proven strategy to mitigate morbidity and mortality of infectious diseases. The methodology of identifying and testing new vaccine candidates could be improved with rational design and in vitro testing prior to animal experimentation. The tularemia vaccine, Francisella tularensis live vaccine strain (LVS, does not elicit complete protection against lethal challenge with a virulent type A Francisella strain. One factor that may contribute to this poor performance is limited stimulation of antigen-presenting cells. In this study, we examined whether the interaction of genetically modified LVS strains with human antigen-presenting cells correlated with effectiveness as tularemia vaccine candidates. Human dendritic cells infected with wild-type LVS secrete low levels of proinflammatory cytokines, fail to upregulate costimulatory molecules, and activate human T cells poorly in vitro. One LVS mutant, strain 13B47, stimulated higher levels of proinflammatory cytokines from dendritic cells and macrophages and increased costimulatory molecule expression on dendritic cells compared to wild type. Additionally, 13B47-infected dendritic cells activated T cells more efficiently than LVS-infected cells. A deletion allele of the same gene in LVS displayed similar in vitro characteristics, but vaccination with this strain did not improve survival after challenge with a virulent Francisella strain. In vivo, this mutant was attenuated for growth and did not stimulate T cell responses in the lung comparable to wild type. Therefore, stimulation of antigen-presenting cells in vitro was improved by genetic modification of LVS, but did not correlate with efficacy against challenge in vivo within this model system.

  13. Safety and protective efficacy of porcine reproductive and respiratory syndrome recombinant virus vaccines in young pigs.

    NARCIS (Netherlands)

    Verheije, M.H.; Kroese, M.V.; Linden, van der I.F.A.; Boer-Luijtze, de E.A.; Rijn, van P.A.; Pol, J.M.A.; Meulenberg, J.J.M.; Steverink, P.J.G.M.

    2003-01-01

    Three porcine reproductive and respiratory syndrome virus (PRRSV) recombinants, generated by mutagenesis of an infectious cDNA clone of the Lelystad virus (LV) isolate, were tested for their safety and protective efficacy as potential PRRSV vaccines in pigs. Recombinant vABV688 contains two amino

  14. Safety and efficacy of influenza vaccination in systemic lupus erythematosus patients with quiescent disease

    NARCIS (Netherlands)

    Holvast, A; Huckriede, A; Wilschut, J; Horst, G; De Vries, JJC; Benne, CA; Kallenberg, CGM; Bijl, M

    Objective: to assess the safety and efficacy of influenza vaccination in patients with systemic lupus erythematosus (SLE), and to evaluate the influence of immunosuppressive drugs on the immune response. Methods: SLE patients (n = 56) and healthy controls (n = 18) were studied. All patients had

  15. Risk Perceptions, Barriers, and Self-Efficacy of Hepatitis B Screening and Vaccination among Chinese Immigrants

    Science.gov (United States)

    Ma, Grace X.; Shive, Steven S.; Toubbeh, Jamil; Wu, Dunli; Wang, Ping

    2006-01-01

    Hepatitis B (HBV) infection is a serious health problem among Asian Americans, including Chinese Americans. This study was conducted to measure the perceptions of risk, barriers, and self-efficacy of HBV screening and vaccination in Chinese immigrants. A cross-sectional study was conducted among 429 Chinese Americans in New York City. A…

  16. Importance of neutralization sieve analyses when seeking correlates of HIV-1 vaccine efficacy.

    Science.gov (United States)

    Montefiori, David C

    2014-01-01

    This commentary describes a rationale for the use of breakthrough viruses from clinical trial participants to assess neutralizing antibodies as a correlate of HIV-1 vaccine efficacy. The rationale is based on principles of a genetic sieve analysis, where the 2 analyses may be cooperative for delineating neutralizing antibodies as a mechanistic correlate of protection.

  17. Strain diversity plays no major role in the varying efficacy of rotavirus vaccines: an overview.

    Science.gov (United States)

    Velasquez, Daniel E; Parashar, Umesh D; Jiang, Baoming

    2014-12-01

    While a monovalent Rotarix® [RV1] and a pentavalent RotaTeq® [RV5] have been extensively tested and found generally safe and equally efficacious in clinical trials, the question still lingers about the evolving diversity of circulating rotavirus strains over time and their relationship with protective immunity induced by rotavirus vaccines. We reviewed data from clinical trials and observational studies that assessed the efficacy or field effectiveness of rotavirus vaccines against different rotavirus strains worldwide. RV1 provided broad clinical efficacy and field effectiveness against severe diarrhea due to all major circulating strains, including the homotypic G1P[8] and the fully heterotypic G2P[4] strains. Similarly, RV5 provided broad efficacy and effectiveness against RV5 and non-RV5 strains throughout different locations. Rotavirus vaccination provides broad heterotypic protection; however continuing surveillance is needed to track the change of circulating strains and monitor the effectiveness and safety of vaccines. Published by Elsevier B.V.

  18. Strategies for differentiating infection in vaccinated animals (DIVA) for foot-and-mouth disease, classical swine fever and avian influenza

    DEFF Research Database (Denmark)

    Uttenthal, Åse; Parida, Satya; Rasmussen, Thomas Bruun

    2010-01-01

    for the presence of infection. This literature review describes the current knowledge on the use of DIVA diagnostic strategies for three important transboundary animal diseases: foot-and-mouth disease in cloven-hoofed animals, classical swine fever in pigs and avian influenza in poultry....

  19. Immunogenicity and efficacy of Hoshino strain of mumps vaccine in Iran; two years study.

    Science.gov (United States)

    Avijgan, M; Hafizi, M; Moghni, M; Kheiri, S; Esteghamati, A; Sarikhani, S

    2011-06-01

    This report describes the immunogenicity and efficacy and long term immunity of Hoshino strain of Mumps (included in MMR Vaccine) in shahr-e-kord, Islamic Republic of Iran (I.R.Iran). A total of 338 Children aged 3-18 years were tested for Mumps IgG using enzyme-linked immunosorbent assay (ELISA). The proportion of susceptible, mumps IgG negative, children was 19.8% (67 subjects). Of the 67 susceptible children, 36 received the MMR vaccination and successfully completed the study. Blood was collected by venipuncture 3, 12, and 24 months after vaccination and serum samples were tested by ELISA for detection of Mumps IgM and IgG. The overall seroconversion rate was 86.1%, 77.7% and 75% at 3, 12, and 24 months after vaccination respectively.

  20. Cyclooxygenase-2 inhibitor enhances the efficacy of a breast cancer vaccine: role of IDO.

    Science.gov (United States)

    Basu, Gargi D; Tinder, Teresa L; Bradley, Judy M; Tu, Tony; Hattrup, Christine L; Pockaj, Barbara A; Mukherjee, Pinku

    2006-08-15

    We report that administration of celecoxib, a specific cyclooxygenase-2 (COX-2) inhibitor, in combination with a dendritic cell-based cancer vaccine significantly augments vaccine efficacy in reducing primary tumor burden, preventing metastasis, and increasing survival. This combination treatment was tested in MMTV-PyV MT mice that develop spontaneous mammary gland tumors with metastasis to the lungs and bone marrow. Improved vaccine potency was associated with an increase in tumor-specific CTLs. Enhanced CTL activity was attributed to a significant decrease in levels of tumor-associated IDO, a negative regulator of T cell activity. We present data suggesting that inhibiting COX-2 activity in vivo regulates IDO expression within the tumor microenvironment; this is further corroborated in the MDA-MB-231 human breast cancer cell line. Thus, a novel mechanism of COX-2-induced immunosuppression via regulation of IDO has emerged that may have implications in designing future cancer vaccines.

  1. Critical Analysis of Compositions and Protective Efficacies of Oral Killed Cholera Vaccines

    Science.gov (United States)

    2014-01-01

    Two cholera vaccines, sold as Shanchol and Dukoral, are currently available. This review presents a critical analysis of the protective efficacies of these vaccines. Children under 5 years of age are very vulnerable to cholera and account for the highest incidence of cholera cases and more than half of the resulting deaths. Both Shanchol and Dukoral are two-spaced-dose oral vaccines comprising large numbers of killed cholera bacteria. The former contains Vibrio cholerae O1 and O139 cells, and the latter contains V. cholerae O1 cells with the recombinant B subunit of cholera toxin. In a field trial in Kolkata (India), Shanchol, the preferred vaccine, protected 45% of the test subjects in all of the age groups and only 17% of the children under 5 years of age during the first year of surveillance. In a field trial in Peru, two spaced doses of Dukoral offered negative protection in children under 5 years of age and little protection (15%) in vaccinees over 6 years of age during the first year of surveillance. Little is known about Dukoral's long-term protective efficacy. Both of these vaccines have questionable compositions, using V. cholerae O1 strains isolated in 1947 that have been inactivated by heat and formalin treatments that may denature protein. Immunological studies revealed Dukoral's reduced and short-lived efficacy, as measured by several immunological endpoints. Various factors, such as the necessity for multiple doses, poor protection of children under 5 years of age, the requirement of a cold supply chain, production costs, and complex logistics of vaccine delivery, greatly reduce the suitability of either of these vaccines for endemic or epidemic cholera control in resource-poor settings. PMID:25056361

  2. Severe acute respiratory syndrome vaccine efficacy in ferrets: whole killed virus and adenovirus-vectored vaccines.

    Science.gov (United States)

    See, Raymond H; Petric, Martin; Lawrence, David J; Mok, Catherine P Y; Rowe, Thomas; Zitzow, Lois A; Karunakaran, Karuna P; Voss, Thomas G; Brunham, Robert C; Gauldie, Jack; Finlay, B Brett; Roper, Rachel L

    2008-09-01

    Although the 2003 severe acute respiratory syndrome (SARS) outbreak was controlled, repeated transmission of SARS coronavirus (CoV) over several years makes the development of a SARS vaccine desirable. We performed a comparative evaluation of two SARS vaccines for their ability to protect against live SARS-CoV intranasal challenge in ferrets. Both the whole killed SARS-CoV vaccine (with and without alum) and adenovirus-based vectors encoding the nucleocapsid (N) and spike (S) protein induced neutralizing antibody responses and reduced viral replication and shedding in the upper respiratory tract and progression of virus to the lower respiratory tract. The vaccines also diminished haemorrhage in the thymus and reduced the severity and extent of pneumonia and damage to lung epithelium. However, despite high neutralizing antibody titres, protection was incomplete for all vaccine preparations and administration routes. Our data suggest that a combination of vaccine strategies may be required for effective protection from this pathogen. The ferret may be a good model for SARS-CoV infection because it is the only model that replicates the fever seen in human patients, as well as replicating other SARS disease features including infection by the respiratory route, clinical signs, viral replication in upper and lower respiratory tract and lung damage.

  3. Efficacy, Immunogenicity and Safety of a Human Rotavirus Vaccine RIX4414 in Singaporean Infants.

    Science.gov (United States)

    Phua, Kong Boo; Lim, Fong Seng; Quak, Seng Hock; Lee, Bee Wah; Teoh, Yee Leong; Suryakiran, Pemmaraju V; Han, Htay Htay; Bock, Hans L

    2016-02-01

    This was the first study conducted to evaluate the efficacy of 2 oral doses of the human rotavirus vaccine, RIX4414 in Singaporean infants during the first 3 years of life. Healthy infants, 11 to 17 weeks of age were enrolled in this randomised (1:1), double-blinded, placebo-controlled study to receive 2 oral doses of RIX4414 vaccine/placebo following a 0-, 1-month schedule. Vaccine efficacy against severe rotavirus (RV) gastroenteritis (Vesikari score ≥11) caused by wild-type RV strains from a period starting from 2 weeks post-Dose 2 until 2 and 3 years of age was calculated with 95% confidence interval (CI). Immunogenicity and safety of the vaccine were also assessed. Of 6542 infants enrolled, 6466 were included in the efficacy analysis and a subset of 100 infants was included in the immunogenicity analysis. Fewer severe RV gastroenteritis episodes were reported in the RIX4414 group when compared to placebo at both 2 and 3 year follow-up periods. Vaccine efficacy against severe RV gastroenteritis at the respective time points were 93.8% (95% CI, 59.9 to 99.9) and 95.2% (95% CI, 70.5 to 99.9). One to 2 months post-Dose 2 of RIX4414, 97.5% (95% CI, 86.8 to 99.9) of infants seroconverted for anti-RV IgA antibodies. The number of serious adverse events recorded from Dose 1 until 3 years of age was similar in both groups. Two oral doses of RIX4414 vaccine was immunogenic and provided high level of protection against severe RV gastroenteritis in Singaporean children, during the first 3 years of life when the disease burden is highest.

  4. 25 years after Vi typhoid vaccine efficacy study, typhoid affects significant number of population in Nepal.

    Directory of Open Access Journals (Sweden)

    Deepak Bajracharya

    Full Text Available Salmonella Typhi, first isolated in 1884, results in infection of the intestines and can end in death and disability. Due to serious adverse events post vaccination, whole cell killed vaccines have been replaced with new generation vaccines. The efficacy of Vi polysaccharide (ViPS vaccine, a new generation, single-dose intramuscular typhoid vaccine was assessed in Nepal in 1987. However, despite the availability of ViPS vaccine for more than 25 years, Nepal has one of the highest incidence of typhoid fever. Therefore we collected information from hospitals in the Kathmandu Valley from over the past five years. There were 9901 enteric fever cases between January 2008 and July 2012. 1,881 of these were confirmed typhoid cases from five hospitals in the Kathmandu district. Approximately 70% of the cases involved children under 15 years old. 1281 cases were confirmed as S. Paratyphi. Vaccines should be prioritized for control of typhoid in conjunction with improved water and sanitation conditions in Nepal and in endemic countries of Asia and Africa.

  5. Epidermal growth factor receptor VIII peptide vaccination is efficacious against established intracerebral tumors.

    Science.gov (United States)

    Heimberger, Amy B; Crotty, Laura E; Archer, Gary E; Hess, Kenneth R; Wikstrand, Carol J; Friedman, Allan H; Friedman, Henry S; Bigner, Darell D; Sampson, John H

    2003-09-15

    The epidermal growth factor receptor (EGFR) is often amplified and structurally rearranged in malignant gliomas and other tumors such as breast and lung, with the most common mutation being EGFRvIII. In the study described here, we tested in mouse models a vaccine consisting of a peptide encompassing the tumor-specific mutated segment of EGFRvIII (PEP-3) conjugated to keyhole limpet hemocyanin [KLH (PEP-3-KLH)]. C57BL/6J or C3H mice were vaccinated with PEP-3-KLH and subsequently challenged either s.c. or intracerebrally with a syngeneic melanoma cell line stably transfected with a murine homologue of EGFRvIII. Control mice were vaccinated with KLH. To test its effect on established tumors, C3H mice were also challenged intracerebrally and subsequently vaccinated with PEP-3-KLH. S.c. tumors developed in all of the C57BL/6J mice vaccinated with KLH in Freund's adjuvant, and there were no long-term survivors. Palpable tumors never developed in 70% of the PEP-3-KLH-vaccinated mice. In the C57BL/6J mice receiving the PEP-3-KLH vaccine, the tumors that did develop were significantly smaller than those in the control group (P PEP-3-KLH vaccination did not result in significant cytotoxic responses in standard cytotoxicity assays; however, antibody titers against PEP-3 were enhanced. The passive transfer of sera from the immunized mice to nonimmunized mice protected 31% of the mice from tumor development (P PEP-3-KLH-vaccinated mice. Peptide vaccination was also sufficiently potent to have marked efficacy against intracerebral tumors, resulting in a >173% increase in median survival time, with 80% of the C3H mice achieving long-term survival (P = 0.014). In addition, C3H mice with established intracerebral tumor that received a single treatment of PEP-3-KLH showed a 26% increase in median survival time, with 40% long-term survival (P = 0.007). Vaccination with an EGFRvIII-specific peptide is efficacious against both s.c. and established intracerebral tumors. The

  6. Key Facts about Seasonal Flu Vaccine

    Science.gov (United States)

    ... Swine Variant Pandemic Other Key Facts About Seasonal Flu Vaccine Language: English (US) Español Recommend on Facebook ... the flu is to get vaccinated each year. Flu Vaccination Why should people get vaccinated against the ...

  7. Comprehensive sieve analysis of breakthrough HIV-1 sequences in the RV144 vaccine efficacy trial.

    Directory of Open Access Journals (Sweden)

    Paul T Edlefsen

    2015-02-01

    Full Text Available The RV144 clinical trial showed the partial efficacy of a vaccine regimen with an estimated vaccine efficacy (VE of 31% for protecting low-risk Thai volunteers against acquisition of HIV-1. The impact of vaccine-induced immune responses can be investigated through sieve analysis of HIV-1 breakthrough infections (infected vaccine and placebo recipients. A V1/V2-targeted comparison of the genomes of HIV-1 breakthrough viruses identified two V2 amino acid sites that differed between the vaccine and placebo groups. Here we extended the V1/V2 analysis to the entire HIV-1 genome using an array of methods based on individual sites, k-mers and genes/proteins. We identified 56 amino acid sites or "signatures" and 119 k-mers that differed between the vaccine and placebo groups. Of those, 19 sites and 38 k-mers were located in the regions comprising the RV144 vaccine (Env-gp120, Gag, and Pro. The nine signature sites in Env-gp120 were significantly enriched for known antibody-associated sites (p = 0.0021. In particular, site 317 in the third variable loop (V3 overlapped with a hotspot of antibody recognition, and sites 369 and 424 were linked to CD4 binding site neutralization. The identified signature sites significantly covaried with other sites across the genome (mean = 32.1 more than did non-signature sites (mean = 0.9 (p < 0.0001, suggesting functional and/or structural relevance of the signature sites. Since signature sites were not preferentially restricted to the vaccine immunogens and because most of the associations were insignificant following correction for multiple testing, we predict that few of the genetic differences are strongly linked to the RV144 vaccine-induced immune pressure. In addition to presenting results of the first complete-genome analysis of the breakthrough infections in the RV144 trial, this work describes a set of statistical methods and tools applicable to analysis of breakthrough infection genomes in general vaccine

  8. Virulence, immunogenicity and vaccine properties of a novel chimeric pestivirus

    DEFF Research Database (Denmark)

    Rasmussen, Thomas Bruun; Uttenthal, Åse; Reimann, Ilona

    2007-01-01

    A chimeric pestivirus of border disease virus Gifhorn and bovine viral diarrhea virus CP7 (Meyers et al., 1996) was constructed. Virulence, immunogenicity and vaccine properties of the chimeric virus were studied in a vaccination–challenge experiment in pigs. The chimeric virus proved...... to be avirulent and neither chimeric virus nor viral RNA was detected in serum after vaccination. The safety of the vaccine was tested by horizontal transmission to sentinel pigs, which remained uninfected. The vaccine efficacy was examined by challenge infection with classical swine fever virus (CSFV) Eystrup...

  9. A boosting skin vaccination with dissolving microneedle patch encapsulating M2e vaccine broadens the protective efficacy of conventional influenza vaccines.

    Science.gov (United States)

    Zhu, Wandi; Pewin, Winston; Wang, Chao; Luo, Yuan; Gonzalez, Gilbert X; Mohan, Teena; Prausnitz, Mark R; Wang, Bao-Zhong

    2017-09-10

    The biodegradable microneedle patch (MNP) is a novel technology for vaccine delivery that could improve the immunogenicity of vaccines. To broaden the protective efficiency of conventional influenza vaccines, a new 4M2e-tFliC fusion protein construct containing M2e sequences from different subtypes was generated. Purified fusion protein was encapsulate into MNPs with a biocompatible polymer for use as a boosting vaccine. The results demonstrated that mice receiving a conventional inactivated vaccine followed by a skin-applied dissolving 4M2e-tFliC MNP boost could better maintain the humoral antibody response than that by the conventional vaccine-prime alone. Compared with an intramuscular injection boost, mice receiving the MNP boost showed significantly enhanced cellular immune responses, hemagglutination-inhibition (HAI) titers, and neutralization titers. Increased frequency of antigen-specific plasma cells and long-lived bone marrow plasma cells was detected in the MNP boosted group as well, indicating that skin vaccination with 4M2e-tFliC facilitated a long-term antibody-mediated immunity. The 4M2e-tFliC MNP-boosted group also possessed enhanced protection against high lethal dose challenges against homologous A/PR/8/34 and A/Aichi/2/68 viruses and protection for a majority of immunized mice against a heterologous A/California/07/2009 H1N1 virus. High levels of M2e specific immune responses were observed in the 4M2e-tFliC MNP-boosted group as well. These results demonstrate that a skin-applied 4M2e-tFliC MNP boosting immunization to seasonal vaccine recipients may be a rapid approach for increasing the protective efficacy of seasonal vaccines in response to a significant drift seen in circulating viruses. The results also provide a new perspective for future exploration of universal influenza vaccines. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Comparison of vaccine efficacy for different antigen delivery systems for infectious pancreatic necrosis virus vaccines in Atlantic salmon (Salmo salar L.) in a cohabitation challenge model.

    Science.gov (United States)

    Munang'andu, Hetron M; Fredriksen, Børge N; Mutoloki, Stephen; Brudeseth, Bjørn; Kuo, Tsun-Yung; Marjara, Inderjit S; Dalmo, Roy A; Evensen, Øystein

    2012-06-08

    Two strains of IPNV made by reverse genetics on the Norwegian Sp strain NVI-015 (GenBank AY379740) backbone encoding the virulent (T(217)A(221)) and avirulent (P(217)T(221)) motifs were used to prepare inactivated whole virus (IWV), nanoparticle vaccines with whole virus, Escherichia coli subunit encoding truncated VP2-TA and VP2-PT, VP2-TA and VP2-PT fusion antigens with putative translocating domains of Pseudomonas aeruginosa exotoxin, and plasmid DNA encoding segment A of the TA strain. Post challenge survival percentages (PCSP) showed that IWV vaccines conferred highest protection (PCSP=42-53) while nanoparticle, sub-unit recombinant and DNA vaccines fell short of the IWV vaccines in Atlantic salmon (Salmo salar L.) postsmolts challenged with the highly virulent Sp strain NVI-015 (TA strain) of IPNV after 560 degree days post vaccination. Antibody levels induced by these vaccines did not show antigenic differences between the virulent and avirulent motifs for vaccines made with the same antigen dose and delivery system after 8 weeks post vaccination. Our findings show that fish vaccinated with less potent vaccines comprising of nanoparticle, DNA and recombinant vaccines got infected much earlier and yielded to higher infection rates than fish vaccinated with IWV vaccines that were highly potent. Ability of the virulent (T(217)A(221)) and avirulent (P(217)T(221)) motifs to limit establishment of infection showed equal protection for vaccines made of the same antigen dose and delivery systems. Prevention of tissue damage linked to viral infection was eminent in the more potent vaccines than the less protective ones. Hence, there still remains the challenge of developing highly efficacious vaccines with the ability to eliminate the post challenge carrier state in IPNV vaccinology. Copyright © 2012 Elsevier Ltd. All rights reserved.

  11. Efficacy, immunogenicity, and safety of a 9-valent human papillomavirus vaccine in Latin American girls, boys, and young women

    OpenAIRE

    Ángela María Ruiz-Sternberg; Edson D. Moreira, Jr; Jaime A. Restrepo; Eduardo Lazcano-Ponce; Robinson Cabello; Arnaldo Silva; Rosires Andrade; Francisco Revollo; Santos Uscanga; Alejandro Victoria; Ana María Guevara; Joaquín Luna; Manuel Plata; Claudia Nossa Dominguez; Edison Fedrizzi

    2018-01-01

    Background: A 9-valent human papillomavirus (HPV6/11/16/18/31/33/45/52/58; 9vHPV) vaccine was developed to expand coverage of the previously developed quadrivalent (HPV6/11/16/18; qHPV) vaccine. Methods: Efficacy, immunogenicity, and safety outcomes were assessed in Latin American participants enrolled in 2 international studies of the 9vHPV vaccine, including a randomized, double-blinded, controlled with qHPV vaccine, efficacy, immunogenicity, and safety study in young women aged 16–26 years...

  12. Vaccination efficacy with marrow mesenchymal stem cell against cancer was enhanced under simulated microgravity

    International Nuclear Information System (INIS)

    Li, Jing; Chen, Jun; Li, Xiuyu; Qian, Yanfang

    2017-01-01

    Stem cell vaccination can induce consistent and strong anti-tumor immunity against cancer in mice model. The antigenic similarity between tumors and embryos has been appreciated for many years and reflects the expression of embryonic gene products by cancer cells and/or cancer-initiating stem cells. Taking advantage of this similarity, we have tested a prophylactic lung cancer vaccine composed of allogeneic murine MSCs. Based on this conception, we first compared their tumor vaccines intervention effects of adult MSCs and MSCs under simulated microgravity (MSC/SMG). In this study, BALB/c mice were vaccinated with MSCs or MSC/SMG, compared with mice vaccinated with phosphate buffered saline (PBS) as negative controls. We then subcutaneously implanted the A549 human lung cancer cell line into vaccinated mice and monitored tumor growth potential in vivo. The smaller tumor size and less tumor weight were observed in mice vaccinated with MSCs or MSC/SMG, compared with that of the Control group. Particularly, it was much more significant in the group of MSC/SMG than that group of the MSCs. Vaccination with SMG treated MSCs inhibited proliferation and promoted apoptosis of tumor tissue. SMG/MSC vaccination induced bothTh1-mediated cytokine response; CD8-dependent cytotoxic response which reduced the proportion of Treg cells. Furthermore, SMG/MSC vaccination significantly increased MHC1 and HSPs proteins expression. In conclusion, we demonstrated the SMG could improve tumor-suppressive activity of MSC. The enhanced anti-tumor immune response of MSCs/SMG was strongly associated with the higher expression of MHC class I molecule on DCs, and the abundance of HSPs in the SMG treated MSCs may make antigens in the MSC more cross-presentable to the host DCs for generating protective antitumor activity. This study gains an insight into the mechanism of MSCs anti-tumor efficacy and gives a new strategy for cancer therapies in the future. - Highlights: • Vaccination with SMG

  13. Multivariate analysis of the immune response to a vaccine as an alternative to the repetition of animal challenge studies for vaccines with demonstrated efficacy.

    Science.gov (United States)

    Chapat, Ludivine; Hilaire, Florence; Bouvet, Jérome; Pialot, Daniel; Philippe-Reversat, Corinne; Guiot, Anne-Laure; Remolue, Lydie; Lechenet, Jacques; Andreoni, Christine; Poulet, Hervé; Day, Michael J; De Luca, Karelle; Cariou, Carine; Cupillard, Lionel

    2017-07-01

    The assessment of vaccine combinations, or the evaluation of the impact of minor modifications of one component in well-established vaccines, requires animal challenges in the absence of previously validated correlates of protection. As an alternative, we propose conducting a multivariate analysis of the specific immune response to the vaccine. This approach is consistent with the principles of the 3Rs (Refinement, Reduction and Replacement) and avoids repeating efficacy studies based on infectious challenges in vivo. To validate this approach, a set of nine immunological parameters was selected in order to characterize B and T lymphocyte responses against canine rabies virus and to evaluate the compatibility between two canine vaccines, an inactivated rabies vaccine (RABISIN ® ) and a combined vaccine (EURICAN ® DAPPi-Lmulti) injected at two different sites in the same animals. The analysis was focused on the magnitude and quality of the immune response. The multi-dimensional picture given by this 'immune fingerprint' was used to assess the impact of the concomitant injection of the combined vaccine on the immunogenicity of the rabies vaccine. A principal component analysis fully discriminated the control group from the groups vaccinated with RABISIN ® alone or RABISIN ® +EURICAN ® DAPPi-Lmulti and confirmed the compatibility between the rabies vaccines. This study suggests that determining the immune fingerprint, combined with a multivariate statistical analysis, is a promising approach to characterizing the immunogenicity of a vaccine with an established record of efficacy. It may also avoid the need to repeat efficacy studies involving challenge infection in case of minor modifications of the vaccine or for compatibility studies. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Development of an Aotus nancymaae Model for Shigella Vaccine Immunogenicity and Efficacy Studies

    Science.gov (United States)

    Gregory, Michael; Lugo-Roman, Luis A.; Galvez Carrillo, Hugo; Tilley, Drake Hamilton; Baldeviano, Christian; Simons, Mark P.; Reynolds, Nathanael D.; Ranallo, Ryan T.; Suvarnapunya, Akamol E.; Venkatesan, Malabi M.; Oaks, Edwin V.

    2014-01-01

    Several animal models exist to evaluate the immunogenicity and protective efficacy of candidate Shigella vaccines. The two most widely used nonprimate models for vaccine development include a murine pulmonary challenge model and a guinea pig keratoconjunctivitis model. Nonhuman primate models exhibit clinical features and gross and microscopic colonic lesions that mimic those induced in human shigellosis. Challenge models for enterotoxigenic Escherichia coli (ETEC) and Campylobacter spp. have been successfully developed with Aotus nancymaae, and the addition of a Shigella-Aotus challenge model would facilitate the testing of combination vaccines. A series of experiments were designed to identify the dose of Shigella flexneri 2a strain 2457T that induces an attack rate of 75% in the Aotus monkey. After primary challenge, the dose required to induce an attack rate of 75% was calculated to be 1 × 1011 CFU. Shigella-specific immune responses were low after primary challenge and subsequently boosted upon rechallenge. However, preexisting immunity derived from the primary challenge was insufficient to protect against the homologous Shigella serotype. A successive study in A. nancymaae evaluated the ability of multiple oral immunizations with live-attenuated Shigella vaccine strain SC602 to protect against challenge. After three oral immunizations, animals were challenged with S. flexneri 2a 2457T. A 70% attack rate was demonstrated in control animals, whereas animals immunized with vaccine strain SC602 were protected from challenge (efficacy of 80%; P = 0.05). The overall study results indicate that the Shigella-Aotus nancymaae challenge model may be a valuable tool for evaluating vaccine efficacy and investigating immune correlates of protection. PMID:24595138

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

    Directory of Open Access Journals (Sweden)

    Attilio Pini

    2008-09-01

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

  16. Points to consider in the development of a surrogate for efficacy of novel Japanese encephalitis virus vaccines.

    Science.gov (United States)

    Markoff, L

    2000-05-26

    Although an effective killed virus vaccine to prevent illness due to Japanese encephalitis virus (JEV) infection exists, many authorities recognize that a safe, effective live JEV vaccine is desirable in order to reduce the cost and the number of doses of vaccine required per immunization. A large-scale clinical efficacy trail for such a vaccine would be both unethical and impractical. Therefore, a surrogate for the efficacy of JE vaccines should be established. Detection of virus-neutralizing antibodies in sera of vaccinees could constitute such a surrogate for efficacy. Field studies of vaccinees in endemic areas and studies done in mice already exist to support this concept. Also, titers of virus-neutralizing antibodies are already accepted as a surrogate for the efficacy of yellow fever virus vaccines and for the efficacy of other viral vaccines as well. In developing a correlation between N antibody titers and protection from JEV infection, standard procedures must be validated and adopted for both measuring N antibodies and for testing in animals. A novel live virus vaccine could be tested in the mouse and/or the monkey model of JEV infection to establish a correlation between virus-neutralizing antibodies elicited by the vaccines and protection from encephalitis. In addition, sera of subjects receiving the novel live JEV vaccine in early clinical trials could be passively transferred to mice or monkeys in order to establish the protective immunogenicity of the vaccine in humans. A monkey model for JEV infection was recently established by scientists at WRAIR in the US. From this group, pools of JEV of known infectivity for Rhesus macaques may be obtained for testing of immunity elicited by live JE vaccine virus.

  17. Safety and Efficacy Data on Vaccines and Immunization to Human Papillomavirus

    Directory of Open Access Journals (Sweden)

    Natalie Kash

    2015-04-01

    Full Text Available Since the discovery of the causal association between human papillomavirus (HPV and cervical cancer, efforts to develop an effective prophylactic vaccine to prevent high-risk HPV infections have been at the forefront of modern medical research. HPV causes 530,000 cervical cancer cases worldwide, which is the second most common cause of cancer deaths in women; a worldwide collaboration among epidemiologists, molecular biologists, vaccinologists, virologists, and clinicians helped lead to the development of two highly effective prophylactive HPV vaccines. The first, Gardasil, is a quadrivalent vaccine made up of recombinant HPV L1 capsid proteins from the two high-risk HPV types (16/18 responsible for 70% of cervical cancer cases as well as two low-risk HPV types (6/11 which are the causative agent for genital warts. The second, Cervarix, is a bivalent vaccine that was FDA approved three years after Gardasil and is also composed of L1 capsid proteins from HPV types 16/18. This review article focuses on the safety and efficacy data of both FDA-approved vaccines, as well as highlighting a few advances in future HPV vaccines that show promise in becoming additional treatment options for this worldwide disease.

  18. Characterization of a novel oil-in-water emulsion adjuvant for swine influenza virus and Mycoplasma hyopneumoniae vaccines

    Science.gov (United States)

    Vaccines consisting of subunit or inactivated bacteria/virus and potent adjuvants are widely used to control and prevent infectious diseases. Because inactivated and subunit antigens are often less antigenic than live microbes, a growing need exists for the development of new and improved vaccine ad...

  19. Immunogenicity and efficacy of a chimpanzee adenovirus-vectored Rift Valley fever vaccine in mice.

    Science.gov (United States)

    Warimwe, George M; Lorenzo, Gema; Lopez-Gil, Elena; Reyes-Sandoval, Arturo; Cottingham, Matthew G; Spencer, Alexandra J; Collins, Katharine A; Dicks, Matthew D J; Milicic, Anita; Lall, Amar; Furze, Julie; Turner, Alison V; Hill, Adrian V S; Brun, Alejandro; Gilbert, Sarah C

    2013-12-05

    Rift Valley Fever (RVF) is a viral zoonosis that historically affects livestock production and human health in sub-Saharan Africa, though epizootics have also occurred in the Arabian Peninsula. Whilst an effective live-attenuated vaccine is available for livestock, there is currently no licensed human RVF vaccine. Replication-deficient chimpanzee adenovirus (ChAd) vectors are an ideal platform for development of a human RVF vaccine, given the low prevalence of neutralizing antibodies against them in the human population, and their excellent safety and immunogenicity profile in human clinical trials of vaccines against a wide range of pathogens. Here, in BALB/c mice, we evaluated the immunogenicity and efficacy of a replication-deficient chimpanzee adenovirus vector, ChAdOx1, encoding the RVF virus envelope glycoproteins, Gn and Gc, which are targets of virus neutralizing antibodies. The ChAdOx1-GnGc vaccine was assessed in comparison to a replication-deficient human adenovirus type 5 vector encoding Gn and Gc (HAdV5-GnGc), a strategy previously shown to confer protective immunity against RVF in mice. A single immunization with either of the vaccines conferred protection against RVF virus challenge eight weeks post-immunization. Both vaccines elicited RVF virus neutralizing antibody and a robust CD8+ T cell response. Together the results support further development of RVF vaccines based on replication-deficient adenovirus vectors, with ChAdOx1-GnGc being a potential candidate for use in future human clinical trials.

  20. Preparation of a standardized, efficacious agricultural H5N3 vaccine by reverse genetics

    International Nuclear Information System (INIS)

    Liu Ming; Wood, John M.; Ellis, Trevor; Krauss, Scott; Seiler, Patrick; Johnson, Christie; Hoffmann, Erich; Humberd, Jennifer; Hulse, Diane; Zhang Yun; Webster, Robert G.; Perez, Daniel R.

    2003-01-01

    Options for the control of emerging and reemerging H5N1 influenza viruses include improvements in biosecurity and the use of inactivated vaccines. Commercially available H5N2 influenza vaccine prevents disease signs and reduces virus load but does not completely prevent virus shedding after challenge with H5N1 virus. By using reverse genetics, we prepared an H5N3 vaccine whose hemagglutinin is 99.6% homologous to that of A/CK/HK/86.3/02 (H5N1). We used the internal genes of A/PR/8/34 and the H5 of A/Goose/HK/437.4/99 (H5N1) after deletion of basic amino acids from its connecting peptide region. The resulting virus was not lethal to chicken embryos and grew to high HA titers in eggs, allowing preparation of HA protein-standardized vaccine in unconcentrated allantoic fluid. The N3 neuraminidase, derived from A/Duck/Germany/1215/73 (H2N3), permitted discrimination between vaccinated and naturally infected birds. The virus construct failed to replicate in quail and chickens. Similar to parental A/PR/8/34 (H1N1), it replicated in mice and ferrets and spread to the brains of mice; therefore, it should not be used as a live-attenuated vaccine. The H5N3 vaccine, at doses of 1.2 μg HA, induced HI antibodies in chickens and prevented death, signs of disease, and markedly reduced virus shedding after challenge with A/CK/HK/86.3/02 (H5N1) but did not provide sterilizing immunity. Thus, reverse genetics allows the inexpensive preparation of standardized, efficacious H5N3 poultry vaccines that may also reduce the reemergence of H5N1 genotypes

  1. New strategies to improve the efficacy of colorectal cancer vaccines: from bench to bedside.

    Science.gov (United States)

    Mocellin, Simone

    2006-12-01

    By exploiting a naturally occurring defense system, anticancer vaccination embodies an ideal non-toxic treatment capable of evoking tumor-specific immune responses that can ultimately recognize and kill colorectal cancer (CRC) cells. Despite the enormous theoretical potential of active specific immunotherapy, no vaccination regimen has achieved sufficient therapeutic efficacy necessary for clinical implementation. Nevertheless, several immunological advances have opened new avenues of research to decipher the biological code governing tumor immune responsiveness, and this is leading to the design of potentially more effective immunotherapeutic protocols. This review briefly summarizes the principles behind anti-CRC vaccination and describes the most promising immunological strategies that have been developed, which are expected to renew interest in this molecularly targeted anticancer approach.

  2. Efficacy of Mycoplasma hyopneumoniae vaccination before and at weaning against experimental challenge infection in pigs.

    Science.gov (United States)

    Arsenakis, Ioannis; Panzavolta, Luca; Michiels, Annelies; Del Pozo Sacristán, Rubén; Boyen, Filip; Haesebrouck, Freddy; Maes, Dominiek

    2016-03-29

    Commercial bacterins are widely used at weaning to control Mycoplasma hyopneumoniae infections in pigs. However, it is not known whether the efficacy of vaccinating against M. hyopneumoniae can be influenced by the weaning process when vaccination is applied at the day of weaning. The present study assessed the efficacy of a single M. hyopneumoniae vaccination (Ingelvac MycoFLEX®) three days before weaning (V1) or at weaning (V2) against experimental challenge infection. Four weeks after vaccination, groups V1 and V2 (n = 20 pigs each) and a non-vaccinated, positive control group (PCG) (n = 20) were endotracheally inoculated with a virulent M. hyopneumoniae field strain. Five pigs were used as a negative control group. All pigs were euthanized 5 weeks after challenge. The main parameters investigated included macroscopic and histopathological lung lesions at necropsy, immunofluorescence (IF) staining and quantitative real-time PCR (qPCR) on broncho-alveolar lavage (BAL) fluid for quantifying M. hyopneumoniae. The average macroscopic lung lesion scores in groups V1, V2 and PCG were 0.54, 0.88 and 1.04, respectively (P > 0.05). The average lymphohistiocytic infiltration scores in groups V1, V2 and PCG were 2.95, 3.16 and 3.61, respectively (P 0.05), the qPCR values were: V1 = 10(2.94), V2 = 10(2.76) and PCG = 10(3.23) (P > 0.05). All pigs of the negative control group remained negative throughout the study. Both vaccinated groups had lower numbers of macroscopic and histopathological lung lesions, and lower numbers of M. hyopneumoniae organisms in the BAL fluid compared to the PCG. However, no firm conclusions could be made on whether weaning negatively influences the efficacy of M. hyopneumoniae vaccination, since significant differences between the treatment groups were only obtained for the histopathological lung lesions. This could be attributed to the fact that milder macroscopic lung lesions were produced in the inoculated pigs, when compared to previous

  3. Efficacy, immunogenicity, and safety of a 9-valent human papillomavirus vaccine in Latin American girls, boys, and young women

    Directory of Open Access Journals (Sweden)

    Ángela María Ruiz-Sternberg

    2018-06-01

    Full Text Available Background: A 9-valent human papillomavirus (HPV6/11/16/18/31/33/45/52/58; 9vHPV vaccine was developed to expand coverage of the previously developed quadrivalent (HPV6/11/16/18; qHPV vaccine. Methods: Efficacy, immunogenicity, and safety outcomes were assessed in Latin American participants enrolled in 2 international studies of the 9vHPV vaccine, including a randomized, double-blinded, controlled with qHPV vaccine, efficacy, immunogenicity, and safety study in young women aged 16–26 years, and an immunogenicity and safety study in girls and boys aged 9–15 years. Participants (N=5312 received vaccination at Day 1, Month 2, and Month 6. Gynecological swabs were collected regularly in young women for cytological and HPV DNA testing. Serum was analyzed for HPV antibodies in all participants. Adverse events (AEs were also monitored in all participants. Results: The 9vHPV vaccine prevented HPV 31-, 33-, 45-, 52-, and 58-related high-grade cervical, vulvar, and vaginal dysplasia with 92.3% efficacy (95% confidence interval 54.4, 99.6. Anti-HPV6, 11, 16, and 18 geometric mean titers at Month 7 were similar in the 9vHPV and qHPV vaccination groups. Anti-HPV antibody responses following vaccination were higher among girls and boys than in young women. Most (>99% 9vHPV vaccine recipients seroconverted for all 9 HPV types at Month 7. Antibody responses to the 9 HPV types persisted over 5 years. The most common AEs were injection-site related, mostly of mild to moderate intensity. Conclusions: The 9vHPV vaccine is efficacious, immunogenic, and well tolerated in Latin American young women, girls, and boys. These data support 9vHPV vaccination programs in Latin America, a region with substantial cervical cancer burden. Keywords: Human papillomavirus, Vaccine, Cervical cancer, Persistent infection, 9vHPV

  4. EFFICACY AND SAFETY OF 23-VALENT PNEUMOCOCCAL POLYSACCHARIDE VACCINE IN PATIENTS WITH RHEUMATOID ARTHRITIS

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    M. S. Naumtseva

    2015-01-01

    Full Text Available Objective: to study the clinical efficacy, immunogenicity, and safety of a 23-valent pneumococcal vaccine in patients with rheumatoid arthritis (RA. Subjects and methods. The investigation enrolled 70 patients (55 women and 15 men aged 23–70 years, including 40 patients with RA and 30 people without systemic inflammatory rheumatic diseases (a control group who had a recent history of 2 and more cases of lower respiratory tract infections (bronchitis, pneumonia. When included, all the patients received anti-inflammatory therapy with methotrexate (MT (n = 24, leflunomide (LEF (n = 6, or MT + tumor necrosis factor-α (TNF-α inhibitors (n = 10. A single 0.5-ml dose of the 23-valent pneumococcal vaccine Pneumo-23 (Sanofi Pasteur was administered subcutaneously or intramuscularly during continuous MT or LEF therapy for the underlying disease or 3–4 weeks before the use of a TNF-α inhibitor. During control visits (1 and 3 months and 1 year after administration of the vaccine, the patients underwent physical examination and routine clinical and laboratory studies. Results. No clinical and radiological symptoms of pneumonia were recorded in any case during a 12-month follow-up. The RA and control groups showed a more than 2-fold increase in anti-pneumococcal antibody levels 1 year after vaccination. The vaccine was well tolerated by 50 patients. Sixteen patients were observed to have pain, cutaneous swelling and hyperemia and 4 had subfebrility. There were neither episodes of RA exacerbation nor new autoimmune disorders during the follow-up. Conclusion. The findings suggest that 23-valent pneumococcal vaccine shows a good clinical efficacy, adequate immunogenicity, and good tolerability in the patients with RA. 

  5. MATHEMATICAL MODELING AS A MODERN TOOL OF PROJECTING THE EFFICACY OF ROTAVIRUS VACCINES

    Directory of Open Access Journals (Sweden)

    S. O. Solovyov

    2012-11-01

    Full Text Available With the use of molecular biological studies there were estimated the peculiarities of the circulation of rotavirus genotypes on the territory of Ukraine. It was estimated predictive genotype-specific efficacy of the vaccine based on rotavirus strain RIX4114 with genotype G1P, based on the methods of distribution and multiplicative synthesis, which were used for the first time in such calculations. This allows obtaining a preliminary evaluation of its efficacy prior to clinical trials. It was established that the calculated value is sufficiently high (80,4% in conditions of its mass use among population of Ukraine.

  6. The capsular group B meningococcal vaccine, 4CMenB : clinical experience and potential efficacy.

    Science.gov (United States)

    Rollier, Christine S; Dold, Christina; Marsay, Leanne; Sadarangani, Manish; Pollard, Andrew J

    2015-01-01

    Capsular group B meningococcal disease is a leading cause of childhood meningitis and septicaemia. Up to 10% of sufferers die, and sequelae remain in > 30% of survivors. A vaccine, four component meningococcal group B ( 4CMenB ), designed with the aim to induce broad coverage against this highly variable bacterium, has been licensed in countries including in the European Union, Canada and Australia. Immunogenicity and safety data, published in peer-reviewed literature between 2004 and 2014, are presented in the context of the recent recommendation for the use of the vaccine in infants in the UK. 4CMenB induces significant reactogenicity when administered with routine infant vaccines, in particular with respect to fever rates. Fevers can be somewhat reduced using paracetamol. The efficacy of the vaccine is unknown but has been extrapolated from effectiveness data obtained from use of one of its components in New Zealand, immunogenicity data from clinical trials and estimation of coverage from in vitro studies. These data suggest that the vaccine will prevent a proportion of invasive meningococcal disease cases in infants and young children. Implementation and well-planned post-marketing surveillance will address uncertainties over field effectiveness.

  7. A multi-antigenic MVA vaccine increases efficacy of combination chemotherapy against Mycobacterium tuberculosis.

    Science.gov (United States)

    Leung-Theung-Long, Stéphane; Coupet, Charles-Antoine; Gouanvic, Marie; Schmitt, Doris; Ray, Aurélie; Hoffmann, Chantal; Schultz, Huguette; Tyagi, Sandeep; Soni, Heena; Converse, Paul J; Arias, Lilibeth; Kleinpeter, Patricia; Sansas, Benoît; Mdluli, Khisimuzi; Vilaplana, Cristina; Cardona, Pere-Joan; Nuermberger, Eric; Marchand, Jean-Baptiste; Silvestre, Nathalie; Inchauspé, Geneviève

    2018-01-01

    Despite the existence of the prophylactic Bacille Calmette-Guérin (BCG) vaccine, infection by Mycobacterium tuberculosis (Mtb) remains a major public health issue causing up to 1.8 million annual deaths worldwide. Increasing prevalence of Mtb strains resistant to antibiotics represents an urgent threat for global health that has prompted a search for alternative treatment regimens not subject to development of resistance. Immunotherapy constitutes a promising approach to improving current antibiotic treatments through engagement of the host's immune system. We designed a multi-antigenic and multiphasic vaccine, based on the Modified Vaccinia Ankara (MVA) virus, denoted MVATG18598, which expresses ten antigens classically described as representative of each of different phases of Mtb infection. In vitro analysis coupled with multiple-passage evaluation demonstrated that this vaccine is genetically stable, i.e. fit for manufacturing. Using different mouse strains, we show that MVATG18598 vaccination results in both Th1-associated T-cell responses and cytolytic activity, targeting all 10 vaccine-expressed Mtb antigens. In chronic post-exposure mouse models, MVATG18598 vaccination in combination with an antibiotic regimen decreases the bacterial burden in the lungs of infected mice, compared with chemotherapy alone, and is associated with long-lasting antigen-specific Th1-type T cell and antibody responses. In one model, co-treatment with MVATG18598 prevented relapse of the disease after treatment completion, an important clinical goal. Overall, results demonstrate the capacity of the therapeutic MVATG18598 vaccine to improve efficacy of chemotherapy against TB. These data support further development of this novel immunotherapeutic in the treatment of Mtb infections.

  8. Characterization of a Cynomolgus Macaque Model of Pneumonic Plague for Evaluation of Vaccine Efficacy.

    Science.gov (United States)

    Fellows, Patricia; Price, Jessica; Martin, Shannon; Metcalfe, Karen; Krile, Robert; Barnewall, Roy; Hart, Mary Kate; Lockman, Hank

    2015-09-01

    The efficacy of a recombinant plague vaccine (rF1V) was evaluated in cynomolgus macaques (CMs) to establish the relationship among vaccine doses, antibody titers, and survival following an aerosol challenge with a lethal dose of Yersinia pestis strain Colorado 92. CMs were vaccinated with a range of rF1V doses on a three-dose schedule (days 0, 56, and 121) to provide a range of survival outcomes. The humoral immune response following vaccination was evaluated with anti-rF1, anti-rV, and anti-rF1V bridge enzyme-linked immunosorbent assays (ELISAs). Animals were challenged via aerosol exposure on day 149. Vaccine doses and antibody responses were each significantly associated with the probability of CM survival (P plague in a dose-dependent manner. There were statistically significant correlations between the vaccine dose and the time to onset of fever (P < 0.0001), the time from onset of fever to death (P < 0.0001), the time to onset of elevated respiratory rate (P = 0.0003), and the time to onset of decreased activity (P = 0.0251) postinfection in animals exhibiting these clinical signs. Delays in the onset of these clinical signs of disease were associated with larger doses of rF1V. Immunization with ≥ 12 μg of rF1V resulted in 100% CM survival. Since both the vaccine dose and anti-rF1V antibody titers correlate with survival, rF1V bridge ELISA titers can be used as a correlate of protection. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  9. Extended Preclinical Safety, Efficacy and Stability Testing of a Live-attenuated Chikungunya Vaccine Candidate.

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    Kenneth S Plante

    Full Text Available We recently described a new, live-attenuated vaccine candidate for chikungunya (CHIK fever, CHIKV/IRES. This vaccine was shown to be well attenuated, immunogenic and efficacious in protecting against CHIK virus (CHIKV challenge of mice and nonhuman primates. To further evaluate its preclinical safety, we compared CHIKV/IRES distribution and viral loads in interferon-α/β receptor-incompetent A129 mice to another CHIK vaccine candidate, 181/clone25, which proved highly immunogenic but mildly reactive in human Phase I/II clinical trials. Compared to wild-type CHIK virus, (wt-CHIKV, both vaccines generated lower viral loads in a wide variety of tissues and organs, including the brain and leg muscle, but CHIKV/IRES exhibited marked restrictions in dissemination and viral loads compared to 181/clone25, and was never found outside the blood, spleen and muscle. Unlike wt-CHIKV, which caused disrupted splenic architecture and hepatic lesions, histopathological lesions were not observed in animals infected with either vaccine strain. To examine the stability of attenuation, both vaccines were passaged 5 times intracranially in infant A129 mice, then assessed for changes in virulence by comparing parental and passaged viruses for footpad swelling, weight stability and survival after subcutaneous infection. Whereas strain 181/clone25 p5 underwent a significant increase in virulence as measured by weight loss (from 30% and mortality (from 0 to 100%, CHIKV/IRES underwent no detectible change in any measure of virulence (no significant weight loss and no mortality. These data indicate greater nonclinical safety of the CHIKV/IRES vaccine candidate compared to 181/clone25, further supporting its eligibility for human testing.

  10. A Mouse Model of Enterovirus D68 Infection for Assessment of the Efficacy of Inactivated Vaccine

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    Chao Zhang

    2018-01-01

    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.

  11. A multi-antigenic MVA vaccine increases efficacy of combination chemotherapy against Mycobacterium tuberculosis.

    Directory of Open Access Journals (Sweden)

    Stéphane Leung-Theung-Long

    Full Text Available Despite the existence of the prophylactic Bacille Calmette-Guérin (BCG vaccine, infection by Mycobacterium tuberculosis (Mtb remains a major public health issue causing up to 1.8 million annual deaths worldwide. Increasing prevalence of Mtb strains resistant to antibiotics represents an urgent threat for global health that has prompted a search for alternative treatment regimens not subject to development of resistance. Immunotherapy constitutes a promising approach to improving current antibiotic treatments through engagement of the host's immune system. We designed a multi-antigenic and multiphasic vaccine, based on the Modified Vaccinia Ankara (MVA virus, denoted MVATG18598, which expresses ten antigens classically described as representative of each of different phases of Mtb infection. In vitro analysis coupled with multiple-passage evaluation demonstrated that this vaccine is genetically stable, i.e. fit for manufacturing. Using different mouse strains, we show that MVATG18598 vaccination results in both Th1-associated T-cell responses and cytolytic activity, targeting all 10 vaccine-expressed Mtb antigens. In chronic post-exposure mouse models, MVATG18598 vaccination in combination with an antibiotic regimen decreases the bacterial burden in the lungs of infected mice, compared with chemotherapy alone, and is associated with long-lasting antigen-specific Th1-type T cell and antibody responses. In one model, co-treatment with MVATG18598 prevented relapse of the disease after treatment completion, an important clinical goal. Overall, results demonstrate the capacity of the therapeutic MVATG18598 vaccine to improve efficacy of chemotherapy against TB. These data support further development of this novel immunotherapeutic in the treatment of Mtb infections.

  12. Artificially synthesized helper/killer-hybrid epitope long peptide (H/K-HELP): preparation and immunological analysis of vaccine efficacy.

    Science.gov (United States)

    Masuko, Kazutaka; Wakita, Daiko; Togashi, Yuji; Kita, Toshiyuki; Kitamura, Hidemitsu; Nishimura, Takashi

    2015-01-01

    To elucidate the immunologic mechanisms of artificially synthesized helper/killer-hybrid epitope long peptide (H/K-HELP), which indicated a great vaccine efficacy in human cancers, we prepared ovalbumin (OVA)-H/K-HELP by conjugating killer and helper epitopes of OVA-model tumor antigen via a glycine-linker. Vaccination of C57BL/6 mice with OVA-H/K-HELP (30 amino acids) but not with short peptides mixture of class I-binding peptide (8 amino-acids) and class II-binding peptide (17 amino-acids) combined with adjuvant CpG-ODN (cytosine-phosphorothioate-guanine oligodeoxynucleotides), induced higher numbers of OVA-tetramer-positive CTL with concomitant activation of IFN-γ-producing CD4(+) Th1 cells. However, replacement of glycine-linker of OVA-H/K-HELP with other peptide-linker caused a significant decrease of vaccine efficacy of OVA-H/K-HELP. In combination with adjuvant CpG-ODN, OVA-H/KHELP exhibited greater vaccine efficacy compared with short peptides vaccine, in both preventive and therapeutic vaccine models against OVA-expressing EG-7 tumor. The elevated vaccine efficacy of OVAH/K-HELP might be derived from the following mechanisms: (i) selective presentation by only professional dendritic cells (DC) in vaccinated draining lymph node (dLN); (ii) a long-term sustained antigen presentation exerted by DC to stimulate both CTL and Th1 cells; (iii) formation of three cells interaction among DC, Th and CTL. In comparative study, H/K-HELP indicated stronger therapeutic vaccine efficacy compared with that of extended class I synthetic long peptide, indicating that both the length of peptide and the presence of Th epitope peptide were crucial aspects for preparing artificially synthesized H/K-HELP vaccine. Copyright © 2014 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

  13. Efficacy, immunogenicity, and safety of a 9-valent human papillomavirus vaccine in Latin American girls, boys, and young women.

    Science.gov (United States)

    Ruiz-Sternberg, Ángela María; Moreira, Edson D; Restrepo, Jaime A; Lazcano-Ponce, Eduardo; Cabello, Robinson; Silva, Arnaldo; Andrade, Rosires; Revollo, Francisco; Uscanga, Santos; Victoria, Alejandro; Guevara, Ana María; Luna, Joaquín; Plata, Manuel; Dominguez, Claudia Nossa; Fedrizzi, Edison; Suarez, Eugenio; Reina, Julio C; Ellison, Misoo C; Moeller, Erin; Ritter, Michael; Shields, Christine; Cashat, Miguel; Perez, Gonzalo; Luxembourg, Alain

    2018-06-01

    A 9-valent human papillomavirus (HPV6/11/16/18/31/33/45/52/58; 9vHPV) vaccine was developed to expand coverage of the previously developed quadrivalent (HPV6/11/16/18; qHPV) vaccine. Efficacy, immunogenicity, and safety outcomes were assessed in Latin American participants enrolled in 2 international studies of the 9vHPV vaccine, including a randomized, double-blinded, controlled with qHPV vaccine, efficacy, immunogenicity, and safety study in young women aged 16-26 years, and an immunogenicity and safety study in girls and boys aged 9-15 years. Participants (N=5312) received vaccination at Day 1, Month 2, and Month 6. Gynecological swabs were collected regularly in young women for cytological and HPV DNA testing. Serum was analyzed for HPV antibodies in all participants. Adverse events (AEs) were also monitored in all participants. The 9vHPV vaccine prevented HPV 31-, 33-, 45-, 52-, and 58-related high-grade cervical, vulvar, and vaginal dysplasia with 92.3% efficacy (95% confidence interval 54.4, 99.6). Anti-HPV6, 11, 16, and 18 geometric mean titers at Month 7 were similar in the 9vHPV and qHPV vaccination groups. Anti-HPV antibody responses following vaccination were higher among girls and boys than in young women. Most (>99%) 9vHPV vaccine recipients seroconverted for all 9 HPV types at Month 7. Antibody responses to the 9 HPV types persisted over 5 years. The most common AEs were injection-site related, mostly of mild to moderate intensity. The 9vHPV vaccine is efficacious, immunogenic, and well tolerated in Latin American young women, girls, and boys. These data support 9vHPV vaccination programs in Latin America, a region with substantial cervical cancer burden. Copyright © 2018 Merck Sharp & Dohme Corp., and The Authors. Published by Elsevier B.V. All rights reserved.

  14. A novel rabies vaccine based-on toll-like receptor 3 (TLR3) agonist PIKA adjuvant exhibiting excellent safety and efficacy in animal studies

    International Nuclear Information System (INIS)

    Zhang, Yi; Zhang, Shoufeng; Li, Wei; Hu, Yuchi; Zhao, Jinyan; Liu, Fang; Lin, Haixiang; Liu, Yuan; Wang, Liliang; Xu, Shu; Hu, Rongliang; Shao, Hui; Li, Lietao

    2016-01-01

    Vaccination alone is not sufficiently effective to protect human from post-exposure rabies virus infection due to delayed generation of rabies virus neutralizing antibodies and weak cellular immunity. Therefore, it is vital to develop safer and more efficacious vaccine against rabies. PIKA, a stabilized chemical analog of double-stranded RNA that interacts with TLR3, was employed as adjuvant of rabies vaccine. The efficacy and safety of PIKA rabies vaccine were evaluated. The results showed that PIKA rabies vaccine enhanced both humoral and cellular immunity. After viral challenge, PIKA rabies vaccine protected 70–80% of animals, while the survival rate of non-adjuvant vaccine group (control) was 20–30%. According to the results of toxicity tests, PIKA and PIKA rabies vaccine are shown to be well tolerated in mice. Thus, this study indicates that PIKA rabies vaccine is an effective and safe vaccine which has the potential to develop next-generation rabies vaccine and encourage the start of clinical studies. - Highlights: • Vaccination alone is not effective to protect human from rabies virus infection due to delayed generation of rabies virus neutralizing antibodies (RVNA) and weak cellular immunity. • Therefore, it is vital to develop safer and more efficacious vaccine against rabies. PIKA, a stabilized chemical analog of double-stranded RNA that interacts with TLR3, was employed as an adjuvant of rabies vaccine. • The efficacy and safety of PIKA rabies vaccine was evaluated in mice. • The results showed that PIKA rabies vaccine enhanced both humoral and cellular immunity. • After viral challenge, PIKA rabies vaccine protected 70–80% of animals, while the survival rate of non-adjuvant vaccine group was only 20–30%. • According to the results of toxicity tests, PIKA and PIKA rabies vaccine are shown to be well tolerated in mice. • Thus, this study indicates that PIKA rabies vaccine is an effective and safe vaccine which has the potential to

  15. A novel rabies vaccine based-on toll-like receptor 3 (TLR3) agonist PIKA adjuvant exhibiting excellent safety and efficacy in animal studies

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yi [Yisheng Biopharma. Co., Ltd., Beijing (China); Zhang, Shoufeng [Academy of Military Medical Sciences, Changchun (China); Li, Wei [National Center for Safety Evaluation of Drugs, Beijing (China); Hu, Yuchi; Zhao, Jinyan [Beijing Institute for Drug Control, Beijing (China); Liu, Fang; Lin, Haixiang; Liu, Yuan; Wang, Liliang; Xu, Shu [Yisheng Biopharma. Co., Ltd., Beijing (China); Hu, Rongliang, E-mail: ronglianghu@hotmail.com [Academy of Military Medical Sciences, Changchun (China); Shao, Hui, E-mail: hui.shao@yishengbio.com [Yisheng Biopharma. Co., Ltd., Beijing (China); Li, Lietao, E-mail: lietao.li@gmail.com [Yisheng Biopharma. Co., Ltd., Beijing (China)

    2016-02-15

    Vaccination alone is not sufficiently effective to protect human from post-exposure rabies virus infection due to delayed generation of rabies virus neutralizing antibodies and weak cellular immunity. Therefore, it is vital to develop safer and more efficacious vaccine against rabies. PIKA, a stabilized chemical analog of double-stranded RNA that interacts with TLR3, was employed as adjuvant of rabies vaccine. The efficacy and safety of PIKA rabies vaccine were evaluated. The results showed that PIKA rabies vaccine enhanced both humoral and cellular immunity. After viral challenge, PIKA rabies vaccine protected 70–80% of animals, while the survival rate of non-adjuvant vaccine group (control) was 20–30%. According to the results of toxicity tests, PIKA and PIKA rabies vaccine are shown to be well tolerated in mice. Thus, this study indicates that PIKA rabies vaccine is an effective and safe vaccine which has the potential to develop next-generation rabies vaccine and encourage the start of clinical studies. - Highlights: • Vaccination alone is not effective to protect human from rabies virus infection due to delayed generation of rabies virus neutralizing antibodies (RVNA) and weak cellular immunity. • Therefore, it is vital to develop safer and more efficacious vaccine against rabies. PIKA, a stabilized chemical analog of double-stranded RNA that interacts with TLR3, was employed as an adjuvant of rabies vaccine. • The efficacy and safety of PIKA rabies vaccine was evaluated in mice. • The results showed that PIKA rabies vaccine enhanced both humoral and cellular immunity. • After viral challenge, PIKA rabies vaccine protected 70–80% of animals, while the survival rate of non-adjuvant vaccine group was only 20–30%. • According to the results of toxicity tests, PIKA and PIKA rabies vaccine are shown to be well tolerated in mice. • Thus, this study indicates that PIKA rabies vaccine is an effective and safe vaccine which has the potential to

  16. Public views of the uk media and government reaction to the 2009 swine flu pandemic

    Directory of Open Access Journals (Sweden)

    Smith Emily

    2010-11-01

    Full Text Available Abstract Background The first cases of influenza A/H1N1 (swine flu were confirmed in the UK on 27th April 2009, after a novel virus first identified in Mexico rapidly evolved into a pandemic. The swine flu outbreak was the first pandemic in more than 40 years and for many, their first encounter with a major influenza outbreak. This study examines public understandings of the pandemic, exploring how people deciphered the threat and perceived they could control the risks. Methods Purposive sampling was used to recruit seventy three people (61 women and 12 men to take part in 14 focus group discussions around the time of the second wave in swine flu cases. Results These discussions showed that there was little evidence of the public over-reacting, that people believed the threat of contracting swine flu was inevitable, and that they assessed their own self-efficacy for protecting against it to be low. Respondents assessed a greater risk to their health from the vaccine than from the disease. Such findings could have led to apathy about following the UK Governments recommended health protective behaviours, and a sub-optimal level of vaccine uptake. More generally, people were confused about the difference between seasonal influenza and swine flu and their vaccines. Conclusions This research suggests a gap in public understandings which could hinder attempts to communicate about novel flu viruses in the future. There was general support for the government's handling of the pandemic, although its public awareness campaign was deemed ineffectual as few people changed their current hand hygiene practices. There was less support for the media who were deemed to have over-reported the swine flu pandemic.

  17. Classical swine fever in pigs: recent developments and future perspectives.

    Science.gov (United States)

    Chander, Vishal; Nandi, S; Ravishankar, C; Upmanyu, V; Verma, Rishendra

    2014-06-01

    Classical swine fever (CSF) is one of the most devastating epizootic diseases of pigs, causing high morbidity and mortality worldwide. The diversity of clinical signs and similarity in disease manifestations to other diseases make CSF difficult to diagnose with certainty. The disease is further complicated by the presence of a number of different strains belonging to three phylogenetic groups. Advanced diagnostic techniques allow detection of antigens or antibodies in clinical samples, leading to implementation of proper and effective control programs. Polymerase chain reaction (PCR)-based methods, including portable real-time PCR, provide diagnosis in a few hours with precision and accuracy, even at the point of care. The disease is controlled by following a stamping out policy in countries where vaccination is not practiced, whereas immunization with live attenuated vaccines containing the 'C' strain is effectively used to control the disease in endemic countries. To overcome the problem of differentiation of infected from vaccinated animals, different types of marker vaccines, with variable degrees of efficacy, along with companion diagnostic assays have been developed and may be useful in controlling and even eradicating the disease in the foreseeable future. The present review aims to provide an overview and status of CSF as a whole with special reference to swine husbandry in India.

  18. The progressive adaptation of a georgian isolate of African swine fever virus to vero cells leads to a gradual attenuation of virulence in swine corresponding to major modifications of the viral genome.

    Science.gov (United States)

    Krug, Peter W; Holinka, Lauren G; O'Donnell, Vivian; Reese, Bo; Sanford, Brenton; Fernandez-Sainz, Ignacio; Gladue, Douglas P; Arzt, Jonathan; Rodriguez, Luis; Risatti, Guillermo R; Borca, Manuel V

    2015-02-01

    African swine fever virus (ASFV) causes a contagious and often lethal disease of feral and domestic swine. Experimental vaccines derived from naturally occurring, genetically modified, or cell culture-adapted ASFV have been evaluated, but no commercial vaccine is available to control African swine fever (ASF). We report here the genotypic and phenotypic analysis of viruses obtained at different passages during the process of adaptation of a virulent ASFV field isolate from the Republic of Georgia (ASFV-G) to grow in cultured cell lines. ASFV-G was successively passaged 110 times in Vero cells. Viruses obtained at passages 30, 60, 80, and 110 were evaluated in vitro for the ability to replicate in Vero cells and primary swine macrophages cultures and in vivo for assessing virulence in swine. Replication of ASFV-G in Vero cells increased with successive passages, corresponding to a decreased replication in primary swine macrophages cultures. In vivo, progressive loss of virus virulence was observed with increased passages in Vero cells, and complete attenuation of ASFV-G was observed at passage 110. Infection of swine with the fully attenuated virus did not confer protection against challenge with virulent parental ASFV-G. Full-length sequence analysis of each of these viruses revealed significant deletions that gradually accumulated in specific areas at the right and left variable ends of the genome. Mutations that result in amino acid substitutions and frameshift mutations were also observed, though in a rather limited number of genes. The potential importance of these genetic changes in virus adaptation/attenuation is discussed. The main problem in controlling ASF is the lack of vaccines. Attempts to produce vaccines by adaptation of ASFV to cultured cell lines have been made. These attempts led to the production of attenuated viruses that conferred only homologous protection. Specifics regarding adaptation of these isolates to cell cultures have been

  19. Improved Patency of Transjugular Intrahepatic Portosystemic Shunt: The Efficacy of Cilostazol for the Prevention of Pseudointimal Hyperplasia in Swine TIPS Models

    International Nuclear Information System (INIS)

    Park, Sang Woo; Cha, In Ho; Kim, Chul Hwan; Jeon, Hae Jeong; Park, Jeong Hee; Hong, Suk Joo; Lee, In Sik

    2007-01-01

    Purpose. To investigate the efficacy of oral administration of cilostazol to inhibit pseudointimal/intimal hyperplasia in swine TIPS models. Methods. Successful TIPS creation was carried out in 11 of 12 healthy young pigs (20-25 kg). In the treatment group (n = 6), both cilostazol and aspirin were administered daily, from the first day of TIPS creation. The control group (n = 5) was administered only aspirin. The animals were followed-up for 2 weeks and then killed. The specimen (including portal vein, hepatic parenchymal tract, hepatic vein, and inferior vena cava) and stents were carefully bisected in a longitudinal fashion. The control group was compared with the treatment group by means of a gross and histologic evaluation of the degree of pseudointimal/intimal hyperplasia in the shunt. Results. At the gross evaluation, the control group showed considerably more pseudointimal/intimal hyperplasia than the treatment group. Using microscopic evaluation, there was a statistically significant difference (p < 0.05) in the mean maximum pseudointimal/intimal hyperplasia thickness between the control group (2.97 ± 0.33 mm) and treatment group (0.73 ± 0.27 mm). Conclusion. Oral administration of cilostazol may have been effective in reducing pseudointimal/intimal hyperplasia in swine TIPS models

  20. Safety and vaccine efficacy of a glycoprotein G deficient strain of infectious laryngotracheitis virus delivered in ovo.

    Science.gov (United States)

    Legione, Alistair R; Coppo, Mauricio J C; Lee, Sang-Won; Noormohammadi, Amir H; Hartley, Carol A; Browning, Glenn F; Gilkerson, James R; O'Rourke, Denise; Devlin, Joanne M

    2012-11-26

    Infectious laryngotracheitis virus (ILTV), an alphaherpesvirus, causes respiratory disease in chickens and is commonly controlled by vaccination with conventionally attenuated vaccines. Glycoprotein G (gG) is a virulence factor in ILTV and a gG deficient strain of ILTV (ΔgG-ILTV) has shown potential for use as a vaccine. In the poultry industry vaccination via drinking water is common, but technology is now available to allow quicker and more accurate in ovo vaccination of embryos at 18 days of incubation. In this study ΔgG-ILTV was delivered to chicken embryos at three different doses (10(2), 10(3) and 10(4) plaque forming units per egg) using manual in ovo vaccination. At 20 days after hatching, birds were challenged intra-tracheally with wild type ILTV and protection was measured. In ovo vaccination was shown to be safe, as there were no developmental differences between birds from hatching up to 20 days of age, as measured by weight gain. The highest dose of vaccine was the most efficacious, resulting in a weight gain not significantly different from unvaccinated/unchallenged birds seven days after challenge. In contrast, birds vaccinated with the lowest dose showed weight gains not significantly different from unvaccinated/challenged birds. Gross pathology and histopathology of the trachea reflected these observations, with birds vaccinated with the highest dose having less severe lesions. However, qPCR results suggested the vaccine did not prevent the challenge virus replicating in the trachea. This study is the first to assess in ovo delivery of a live attenuated ILTV vaccine and shows that in ovo vaccination with ΔgG-ILTV can be both safe and efficacious. Copyright © 2012 Elsevier Ltd. All rights reserved.

  1. Efficacy of oral BCG vaccination in protecting free-ranging cattle from natural infection by Mycobacterium bovis.

    Science.gov (United States)

    Nugent, Graham; Yockney, Ivor J; Whitford, Jackie; Aldwell, Frank E; Buddle, Bryce M

    2017-09-01

    Vaccination of cattle against bovine tuberculosis could be a valuable control strategy, particularly in countries faced with intractable ongoing infection from a disease reservoir in wildlife. A field vaccination trial was undertaken in New Zealand. The trial included 1286 effectively free-ranging cattle stocked at low densities in a remote 7600ha area, with 55% of them vaccinated using Mycobacterium bovis BCG (Danish strain 1311). Vaccine was administered orally in all but 34 cases (where it was injected). After inclusion, cattle were exposed to natural sources of M. bovis infection in cattle and wildlife, most notably the brushtail possum (Trichosurus vulpecula). Cattle were slaughtered at 3-5 years of age and were inspected for tuberculous lesions, with mycobacteriological culture of key tissues from almost all animals. The prevalence of M. bovis infection was 4.8% among oral BCG vaccinates, significantly lower than the 11.9% in non-vaccinates. Vaccination appeared to both reduce the incidence of detectable infection, and to slow disease progression. Based on apparent annual incidence, the protective efficacy of oral BCG vaccine was 67.4% for preventing infection, and was higher in cattle slaughtered soon after vaccination. Skin-test reactivity to tuberculin was high in vaccinates re-tested 70days after vaccination but not in non-vaccinates, although reactor animals had minimal response in gamma-interferon blood tests. In re- tests conducted more than 12 months after vaccination, skin-test reactivity among vaccinates was much lower. These results indicate that oral BCG vaccination could be an effective tool for greatly reducing detectable infection in cattle. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Characterization and efficacy determination of commercially available Central American H5N2 avian influenza vaccines for poultry.

    Science.gov (United States)

    Eggert, Dawn; Thomas, Colleen; Spackman, Erica; Pritchard, Nikki; Rojo, Francisco; Bublot, Michel; Swayne, David E

    2010-06-23

    A poultry vaccination program was implemented in Central America beginning in January 1995 to control both H5N2 low (LPAI) and high pathogenicity avian influenza. This study was conducted to identify seed strain composition and the efficacy of 10 commercially available H5 vaccines against challenge with H5N2 LPAI viruses isolated from Latin America in 2003. The original 1994 vaccine seed virus in commercial inactivated vaccines did not significantly reduce challenge virus shed titers. However, two seed strains of inactivated vaccines, genetically more closely related to the challenge virus, did significantly reduce titers of challenge virus shed from respiratory tract. In addition, a live recombinant fowlpox virus vaccine containing a more distantly related Eurasian lineage H5 gene insert significantly reduced respiratory shedding as compared to sham vaccinates. These results demonstrate the feasibility of identifying vaccine seed strains in commercial finished products for regulatory verification and the need for periodic challenge testing against current field strains in order to select efficacious vaccine seed strains. (c) 2010 Elsevier Ltd. All rights reserved.

  3. The potential impact of a single amino-acid substitution on the efficacy of equine influenza vaccines.

    Science.gov (United States)

    Yamanaka, T; Cullinane, A; Gildea, S; Bannai, H; Nemoto, M; Tsujimura, K; Kondo, T; Matsumura, T

    2015-07-01

    The protection induced by an equine influenza (EI) vaccine strain depends on its antigenic relatedness to the challenge virus. Although the World Organisation for Animal Health (OIE) recommend that both Florida sublineage clade 1 (Fc1) and clade 2 (Fc2) viruses should be included in EI vaccines, Japanese EI vaccines have not, thus far, been updated to include a Fc2 virus. To evaluate the efficacy of antibodies raised against Japanese EI vaccine strains in the neutralisation of recent Fc2 viruses. Antigenic analysis. Virus neutralisation tests were performed using antisera from experimentally infected horses and from horses that had received a primary course of the currently available vaccines. Antiserum raised against the Japanese EI vaccine strain, A/equine/La Plata/1993, exhibited poor cross-neutralising activity against the Fc2 viruses isolated recently in Ireland and the UK, which have the substitution of alanine to valine at position 144 in antigenic site A of the haemagglutinin gene. In contrast, the antiserum exhibited good cross-neutralising activity against the Fc2 viruses without the substitution. This finding was supported in experiments with antisera collected from vaccinated horses. This suggests that the efficacy of the Japanese EI vaccine for some of the recent Fc2 viruses is suboptimal and that vaccines should be updated in accordance with the OIE recommendations. © 2014 EVJ Ltd.

  4. Increase in DNA vaccine efficacy by virosome delivery and co-expression of a cytolytic protein.

    Science.gov (United States)

    Gargett, Tessa; Grubor-Bauk, Branka; Miller, Darren; Garrod, Tamsin; Yu, Stanley; Wesselingh, Steve; Suhrbier, Andreas; Gowans, Eric J

    2014-06-01

    The potential of DNA vaccines has not been realised due to suboptimal delivery, poor antigen expression and the lack of localised inflammation, essential for antigen presentation and an effective immune response to the immunogen. Initially, we examined the delivery of a DNA vaccine encoding a model antigen, luciferase (LUC), to the respiratory tract of mice by encapsulation in a virosome. Virosomes that incorporated influenza virus haemagglutinin effectively delivered DNA to cells in the mouse respiratory tract and resulted in antigen expression and systemic and mucosal immune responses to the immunogen after an intranasal (IN) prime/intradermal (ID) boost regimen, whereas a multidose ID regimen only generated systemic immunity. We also examined systemic immune responses to LUC after ID vaccination with a DNA vaccine, which also encoded one of the several cytolytic or toxic proteins. Although the herpes simplex virus thymidine kinase, in the presence of the prodrug, ganciclovir, resulted in cell death, this failed to increase the humoral or cell-mediated immune responses. In contrast, the co-expression of LUC with the rotavirus non-structural protein 4 (NSP4) protein or a mutant form of mouse perforin, proteins which are directly cytolytic, resulted in increased LUC-specific humoral and cell-mediated immunity. On the other hand, co-expression of LUC with diphtheria toxin subunit A or overexpression of perforin or NSP4 resulted in a lower level of immunity. In summary, the efficacy of DNA vaccines can be improved by targeted IN delivery of DNA or by the induction of cell death in vaccine-targeted cells after ID delivery.

  5. Secondary efficacy endpoints of the pentavalent rotavirus vaccine against gastroenteritis in sub-Saharan Africa.

    Science.gov (United States)

    Tapia, Milagritos D; Armah, George; Breiman, Robert F; Dallas, Michael J; Lewis, Kristen D C; Sow, Samba O; Rivers, Stephen B; Levine, Myron M; Laserson, Kayla F; Feikin, Daniel R; Victor, John C; Ciarlet, Max; Neuzil, Kathleen M; Steele, A Duncan

    2012-04-27

    The efficacy of the pentavalent rotavirus vaccine (PRV), RotaTeq(®), was evaluated in a double-blind, placebo-controlled, multicenter Phase III clinical trial conducted (April 2007-March 2009) in 3 low-income countries in Africa: Ghana, Kenya, and Mali. In total, 5468 infants were randomized 1:1 to receive 3 doses of PRV/placebo at approximately 6, 10, and 14 weeks of age; concomitant administration with routine EPI vaccines, including OPV, was allowed. HIV-infected infants were not excluded. The primary endpoint, vaccine efficacy (VE) against severe-rotavirus gastroenteritis (RVGE), as measured by Vesikari scoring system (VSS, score ≥11), from ≥14 days following Dose 3 through a follow-up period of nearly 2 years in the combined 3 African countries, and secondary endpoints by total follow-up period have been previously reported. In this study, we report post hoc subgroup analyses on secondary endpoints of public health importance. VE against RVGE of any severity was 49.2% (95%CI: 29.9, 63.5) through the first year of life and 30.5% (95%CI: 16.7, 42.2) through the complete follow-up period. VE against severe-gastroenteritis of any etiology was 21.5% (95%CI: vaccine-contained G and P types (G1-G4, P1A[8]), (ii) non-vaccine G types (G8, G9, G10), and (iii) non-vaccine P types (P1B[4], P2A[6]) was 34.0% (95%CI:11.2, 51.2), 81.8% (95%CI:16.5, 98.0) and 40.7% (95%CI:8.4, 62.1), respectively. There was a trend towards higher VE with higher disease severity, although in some cases the numbers were small. In African countries with high under-5 mortality rates, PRV significantly reduced RVGE through nearly 2 years of follow-up; more modest reductions were observed against gastroenteritis of any etiology. PRV provides protection against severe-RVGE caused by diverse rotavirus genotypes, including those not contained in the vaccine. Copyright © 2012 Elsevier Ltd. All rights reserved.

  6. MANAGEMENT PATIENT OF SWINE INFLUENZA

    Directory of Open Access Journals (Sweden)

    Endra Gunawan

    2015-05-01

    Full Text Available Influenza is an acute respiratory diseases caused by various influenza virus which infect the upper and lower respiratory tract and often accompanied by systemic symptoms such as fever, headache and muscle pain. Influenza spreads through the air. Swine influenza comes from swine and can cause an outbreaks in pig flocks. Even this is a kind of a rare case but the swine influenza could be transmitted to human by direct contact with infected swine or through environment that already being contaminated by swine influenza virus. There are 3 types of swine influenza virus namely H1N1, H3N2 and H1N2. Type H1N1 swine-virus had been known since 1918. Avian influenza virus infection is transmitted from one person to another through secret containing virus. Virus is binded into the mucous cells of respiratory tract before it is finally infecting the cells itself. Management patients with H1N1 influenza is based on the complications and the risk. Besides, it is also need to consider the clinical criteria of the patient. Therapy medicamentosa is applied to the patients by giving an antiviral, antibiotics and symptomatic therapy. Prevention can be done by avoid contact with infected animal or environment, having antiviral prophylaxis and vaccination.

  7. EFFICACY OF VACCINE PREVENTION OF HPV-ASSOCIATED DISEASES AND CERVICAL CANCER IN THE MOSCOW REGION

    Directory of Open Access Journals (Sweden)

    V. I. Krasnopol'skiy

    2015-01-01

    Full Text Available Data on high prevalence of papilloma virus infection and associated disorders in adults as well as in adolescents are becoming more and more frequently published in the world and domestic literature. The most severe outcome of the infection is cervical cancer which takes the second place in women of reproductive age. At present, the armamentarium of obstetricians, gynecologists, pediatricians and oncologists is enriched by a recombinant vaccine protecting against human papilloma virus and representing one of effective methods of prevention of HPV-associated disorders. There are two prophylactic vaccines in the world (quadrivalent Gardasil® and bivalent Cervarix®, which are used in 44 countries. One of the first results proving efficacy of vaccination is a decrease of incidence of anogenital warts that is well described in foreign literature. In the Moscow region, as a result of vaccination performed from 2008 to 2013, a decrease of incidence of anogenital warts in girls is also observed.

  8. Efficacy and safety of a new intradermal PCV2 vaccine in pigs

    Directory of Open Access Journals (Sweden)

    M. Sno

    2016-01-01

    Vaccination with Porcilis® PCV ID resulted in small transient local reactions in a high percentage of the vaccinated animals with no temperature increase. In both the onset of immunity and duration of immunity challenge studies with PCV2 or M. hyopneumoniae, significant reduction of the PCV2 load in lymphoid tissue, lungs, serum and fecal swabs and M. hyopneumoniae-induced lung lesions were observed. In two field trials on two different farms where both PCV2 and M. hyopneumoniae were present, vaccination with Porcilis® PCV ID and/or Porcilis® M Hyo ID ONCE of 3 week old piglets resulted in a significant reduction of PCV2 viraemia, mortality and lung lesion scores at slaughter. In addition, a significant positive effect on average daily weight gain (between 44 and 59 g/day in the finishing phase was observed. The results support that this new intradermal vaccine is safe and efficacious against PCV2 and may be used concurrently with Porcilis® M Hyo ID ONCE.

  9. Observational study of vaccine efficacy 24 years after the start of hepatitis B vaccination in two Gambian villages: no need for a booster dose.

    Directory of Open Access Journals (Sweden)

    Maimuna Mendy

    Full Text Available To determine the duration of protection from hepatitis B vaccine given in infancy and early childhood and asses risk factors for HBV infection and chronic infection.In 1984 infant HBV vaccination was started in two Gambian villages. Cross sectional serological surveys have been undertaken every 4 years to determine vaccine efficacy. In the current survey 84.6% of 1508 eligible participants aged 1-28 years were tested. A spouse study was conducted in females (aged 14 years and above and their male partners.Vaccine efficacy against chronic infection with hepatitis B virus was 95.1% (95% confidence interval 91.5% to 97.1%, which did not vary significantly between age groups or village. Efficacy against infection was 85.4% (82.7% to 87.7%, falling significantly with age. Concentrations of hepatitis B antibody fell exponentially with age varying according to peak response: 20 years after vaccination only 17.8% (95% CI 10.1-25.6 of persons with a low peak response (10-99 mIU/ml had detectable HBs antibody compared to 27% (21.9% to 32.2% of those with a high peak response (>999 mIU/ml. Time since vaccination and a low peak response were the strongest risk factors for HBV infections; males were more susceptible, marriage was not a significant risk for females. Hepatitis B DNA was not detected after infection, which tested soley core antibody positive. An undetectable peak antibody response of <10 mIU/ml and a mother who was hepatitis B e antigen positive were powerful risk factors for chronic infection.Adolescents and young adults vaccinated in infancy are at increased risk of hepatitis B infection, but not chronic infection. Married women were not at increased risk. There is no compelling evidence for the use of a booster dose of HBV vaccine in The Gambia.

  10. Hapten-specific naïve B cells are biomarkers of vaccine efficacy against drugs of abuse.

    Science.gov (United States)

    Taylor, J J; Laudenbach, M; Tucker, A M; Jenkins, M K; Pravetoni, M

    2014-03-01

    Vaccination against drugs of abuse shows efficacy in animal models, yet few subjects achieve effective serum antibody titers in clinical studies. A barrier to translation is the lack of pre-vaccination screening assays that predict the most effective conjugate vaccines or subjects amenable to vaccination. To address this obstacle, we developed a fluorescent antigen-based enrichment method paired with flow cytometry to characterize hapten-specific B cells. Using this approach, we studied naïve and activated B cells specific for structurally-related model haptens based on derivatization of the morphinan structure at the C6 position on oxycodone or at the C8 position on hydrocodone, and showing different pre-clinical efficacy against the prescription opioid oxycodone. Prior to vaccination, naïve B cells exhibited relatively higher affinity for the more effective C6-derivatized oxycodone-based hapten (6OXY) and the 6OXY-specific naïve B cell population contained a higher number of B cells with greater affinity for free oxycodone. Higher affinity of naïve B cells for hapten or oxycodone reflected greater efficacy of vaccination in blocking oxycodone distribution to brain in mice. Shortly after immunization, activated hapten-specific B cells were detected prior to oxycodone-specific serum antibodies and provided earlier evidence of vaccine failure or success. Analysis of hapten-specific naïve and activated B cells may aid rational vaccine design and provide screening tools to predict vaccine clinical efficacy against drugs of abuse or other small molecules. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. Four year efficacy of prophylactic human papillomavirus quadrivalent vaccine against low grade cervical, vulvar, and vaginal intraepithelial neoplasia and anogenital warts: randomised controlled trial

    DEFF Research Database (Denmark)

    Dillner, Joakim; Kjaer, Susanne K; Wheeler, Cosette M

    2010-01-01

    To evaluate the prophylactic efficacy of the human papillomavirus (HPV) quadrivalent vaccine in preventing low grade cervical, vulvar, and vaginal intraepithelial neoplasias and anogenital warts (condyloma acuminata)....

  12. The Recombinant Bacille Calmette–Guérin Vaccine VPM1002: Ready for Clinical Efficacy Testing

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    Natalie E. Nieuwenhuizen

    2017-09-01

    Full Text Available The only licensed vaccine against tuberculosis (TB, bacille Calmette–Guérin (BCG, protects against severe extrapulmonary forms of TB but is virtually ineffective against the most prevalent form of the disease, pulmonary TB. BCG was genetically modified at the Max Planck Institute for Infection Biology to improve its immunogenicity by replacing the urease C encoding gene with the listeriolysin encoding gene from Listeria monocytogenes. Listeriolysin perturbates the phagosomal membrane at acidic pH. Urease C is involved in neutralization of the phagosome harboring BCG. Its depletion allows for rapid phagosome acidification and promotes phagolysosome fusion. As a result, BCGΔureC::hly (VPM1002 promotes apoptosis and autophagy and facilitates release of mycobacterial antigens into the cytosol. In preclinical studies, VPM1002 has been far more efficacious and safer than BCG. The vaccine was licensed to Vakzine Projekt Management and later sublicensed to the Serum Institute of India Pvt. Ltd., the largest vaccine producer in the world. The vaccine has passed phase I clinical trials in Germany and South Africa, demonstrating its safety and immunogenicity in young adults. It was also successfully tested in a phase IIa randomized clinical trial in healthy South African newborns and is currently undergoing a phase IIb study in HIV exposed and unexposed newborns. A phase II/III clinical trial will commence in India in 2017 to assess efficacy against recurrence of TB. The target indications for VPM1002 are newborn immunization to prevent TB as well as post-exposure immunization in adults to prevent TB recurrence. In addition, a Phase I trial in non-muscle invasive bladder cancer patients has been completed, and phase II trials are ongoing. This review describes the development of VPM1002 from the drawing board to its clinical assessment.

  13. Long-Term Single-Dose Efficacy of a Vesicular Stomatitis Virus-Based Andes Virus Vaccine in Syrian Hamsters

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    Joseph Prescott

    2014-01-01

    Full Text Available Andes virus (ANDV is highly pathogenic in humans and is the primary etiologic agent of hantavirus cardiopulmonary syndrome (HCPS in South America. Case-fatality rates are as high as 50% and there are no approved vaccines or specific therapies for infection. Our laboratory has recently developed a replication-competent recombinant vesicular stomatitis virus (VSV-based vaccine that expressed the glycoproteins of Andes virus in place of the native VSV glycoprotein (G. This vaccine is highly efficacious in the Syrian hamster model of HCPS when given 28 days before challenge with ANDV, or when given around the time of challenge (peri-exposure, and even protects when administered post-exposure. Herein, we sought to test the durability of the immune response to a single dose of this vaccine in Syrian hamsters. This vaccine was efficacious in hamsters challenged intranasally with ANDV 6 months after vaccination (p = 0.025, but animals were not significantly protected following 1 year of vaccination (p = 0.090. The decrease in protection correlated with a reduction of measurable neutralizing antibody responses, and suggests that a more robust vaccination schedule might be required to provide long-term immunity.

  14. INFLUENZA AND PNEUMOCOCCAL VACCINATION IN HEMATOLOGICAL MALIGNANCIES: A SYSTEMATIC REVIEW OF EFFICACY, EFFECTIVENESS AND SAFETY

    Directory of Open Access Journals (Sweden)

    Giuseppe La Torre

    2016-09-01

    Full Text Available Background The risk of getting influenza and pneumococcal disease is higher in cancer patients and serum antibody levels tend to be lower in patients with hematological malignancy. Objective To asses flu and pneumococcal vaccinations efficacy, effectiveness and safety in onco-hematological patients. Methods Two systematic reviews and possible meta-analysis were conducted to summarize the results of all primary study in scientific literature about flu and pneumococcal vaccine in onco-hematological patients. Literature searches were performed using Pub-Med and Scopus databases. StatsDirect 2.8.0 was used for the analysis. Results 23 and 26 studies were collected respectively for flu and pneumococcal vaccinations. Protection rate of booster dose was 30% (95% CI = 6.2- 61% for H1N1. Pooled prevalence protection rate of H3N2 and B was available for meta-analysis only for first dose, 42.6% (95% CI = 23.2 – 63.3 % and 39.6 % (95% CI = 26%- 54.1% for H3N2 and B, respectively. Response rate of booster dose resulted 35% (95% CI = 19.7-51.2% for H1N1, 23% (95% CI = 16.6-31.5% for H3N2, 29% (95% CI = 21.3- 37% for B. Conclusion Despite low rate of response, flu and pneumococcal vaccines are worthwhile for patients with hematological malignancies. Patients undergoing chemotherapy in particular rituximab, splenectomy, transplant recipient had lower and impaired response. No serious adverse events were reported for both vaccines.

  15. Are the Two Human Papillomavirus Vaccines Really Similar? A Systematic Review of Available Evidence: Efficacy of the Two Vaccines against HPV

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    Simona Di Mario

    2015-01-01

    Full Text Available Background. When the bivalent and the quadrivalent HPV vaccines were marketed they were presented as having comparable efficacy against cervical cancer. Differences between the vaccines are HPV types included and formulation of the adjuvant. Method. A systematic review was conducted to assess the efficacy of the two vaccines against cervical cancer. Outcomes considered were CIN2+, CIN3+, and AIS. Results. Nine reports (38,419 women were included. At enrolment mean age of women was 20 years, 90% had negative cytology, and 80% were seronegative and/or DNA negative for HPV 16 or 18 (naïve women. In the TVC-naïve, VE against CIN2+ was 58% (95% CI: 35, 72; heterogeneity was detected, VE being 65% (95% CI: 54, 74 for the bivalent and 43% (95% CI: 23, 57 for the quadrivalent. VE against CIN3+ was 78% (95% CI: <0, 97; heterogeneity was substantial, VE being 93% (95% CI: 77, 98 for the bivalent and 43% (95% CI: 12, 63 for the quadrivalent. VE in the TVC was much lower. No sufficient data were available on AIS. Conclusions. In naïve girls bivalent vaccine shows higher efficacy, even if the number of events detected is low. In women already infected the benefit of the vaccination seems negligible.

  16. Efficacy of a monovalent human-bovine (116E) rotavirus vaccine in Indian children in the second year of life.

    Science.gov (United States)

    Bhandari, Nita; Rongsen-Chandola, Temsunaro; Bavdekar, Ashish; John, Jacob; Antony, Kalpana; Taneja, Sunita; Goyal, Nidhi; Kawade, Anand; Kang, Gagandeep; Rathore, Sudeep Singh; Juvekar, Sanjay; Muliyil, Jayaprakash; Arya, Alok; Shaikh, Hanif; Abraham, Vinod; Vrati, Sudhanshu; Proschan, Michael; Kohberger, Robert; Thiry, Georges; Glass, Roger; Greenberg, Harry B; Curlin, George; Mohan, Krishna; Harshavardhan, G V J A; Prasad, Sai; Rao, T S; Boslego, John; Bhan, Maharaj Kishan

    2014-08-11

    Rotavirus gastroenteritis is one of the leading causes of diarrhea in Indian children less than 2 years of age. The 116E rotavirus strain was developed as part of the Indo-US Vaccine Action Program and has undergone efficacy trials. This paper reports the efficacy and additional safety data in children up to 2 years of age. In a double-blind placebo controlled multicenter trial, 6799 infants aged 6-7 weeks were randomized to receive three doses of an oral human-bovine natural reassortant vaccine (116E) or placebo at ages 6, 10, and 14 weeks. The primary outcome was severe (≥11 on the Vesikari scale) rotavirus gastroenteritis. Efficacy outcomes and adverse events were ascertained through active surveillance. We randomly assigned 4532 and 2267 subjects to receive vaccine and placebo, respectively, with over 96% subjects receiving all three doses of the vaccine or placebo. The per protocol analyses included 4354 subjects in the vaccine and 2187 subjects in the placebo group. The overall incidence of severe RVGE per 100 person years was 1.3 in the vaccine group and 2.9 in the placebo recipients. Vaccine efficacy against severe rotavirus gastroenteritis in children up to 2 years of age was 55.1% (95% CI 39.9 to 66.4; pvaccine efficacy in the second year of life of 48.9% (95% CI 17.4 to 68.4; p=0.0056) was only marginally less than in the first year of life [56.3% (95% CI 36.7 to 69.9; pvaccine dose and all were reported only after the third dose. The sustained efficacy of the 116E in the second year of life is reassuring. The trial is registered with Clinical Trial Registry-India (# CTRI/2010/091/000102) and Clinicaltrials.gov (# NCT01305109). Copyright © 2014. Published by Elsevier Ltd.

  17. Comparison of immune responses against foot-and-mouth disease virus induced by fusion proteins using the swine IgG heavy chain constant region or β-galactosidase as a carrier of immunogenic epitopes

    International Nuclear Information System (INIS)

    Li Guangjin; Chen Weizao; Yan Weiyao; Zhao Kai; Liu Mingqiu; Zhang Jun; Fei Liang; Xu Quanxing; Sheng Zutian; Lu Yonggan; Zheng Zhaoxin

    2004-01-01

    Previously, we demonstrated that a fusion protein (Gal-FMDV) consisting of β-galactosidase and an immunogenic peptide, amino acids (141-160)-(21-40)-(141-160), of foot-and-mouth disease virus (FMDV) VP1 protein induced protective immune responses in guinea pigs and swine. We now designed a new potential recombinant protein vaccine against FMDV in swine. The immunogenic peptide, amino acids (141-160)-(21-40)-(141-160) from the VP1 protein of serotype O FMDV, was fused to the carboxy terminus of a swine immunoglobulin G single heavy chain constant region and expressed in Escherichia coli. The expressed fusion protein (IgG-FMDV) was purified and emulsified with oil adjuvant. Vaccination twice at an interval of 3 weeks with the emulsified IgG-FMDV fusion protein induced an FMDV-specific spleen proliferative T-cell response in guinea pigs and elicited high levels of neutralizing antibody in guinea pigs and swine. All of the immunized animals were efficiently protected against FMDV challenge. There was no significant difference between IgG-FMDV and Gal-FMDV in eliciting immunity after vaccination twice in swine. However, when evaluating the efficacy of a single inoculation of the fusion proteins, we found that IgG-FMDV could elicit a protective immune response in swine, while Gal-FMDV only elicited a weak neutralizing activity and could not protect the swine against FMDV challenge. Our results suggest that the IgG-FMDV fusion protein is a promising vaccine candidate for FMD in swine

  18. Virological confirmation of suspected dengue in a Phase 2 Latin American vaccine trial: Implications for vaccine efficacy evaluation

    Directory of Open Access Journals (Sweden)

    Mark Boaz

    2014-01-01

    Full Text Available The CYD tetravalent dengue vaccine candidate is being evaluated for protective efficacy against symptomatic dengue in Phase 3 efficacy trials. The laboratory test algorithm to confirm dengue cases was evaluated prior to Phase 3 trials. During a Phase 2 trial in Latin America a dengue epidemic occurred in the study countries. A total of 72 suspected dengue cases were reported and assessed: virological confirmation comprised qRT-PCR methods and a commercial ELISA kit for NS1 protein (Bio-Rad. The qRT-PCR included a screening assay targeting a conserved dengue region of the 3′-UTR (dengue screen assay followed by 4 individual serotype assays targeting the conserved dengue NS5 genomic region (WT dengue qRT-PCR assays. The NS1 and WT dengue qRT-PCR were endpoint assays for protocol virological confirmation (PVC. Of the 72 suspected cases, 14 were PVC. However, a unique pattern of dengue qRT-PCR results were observed in 5 suspected cases from Honduras: the dengue screen qRT-PCR assay was positive but WT dengue qRT-PCR and NS1 Ag ELISA were negative. To investigate these observations, additional molecular methods were applied: a SYBR® Green-based RT-PCR assay, sequencing assays directed at the genome regions covered by the WT dengue qRT-PCR, and a modified commercial dengue RT-PCR test (Simplexa™ Dengue, Focus Diagnostics. The exploratory data confirmed these additional cases as dengue and indicated the serotype 2 WT dengue qRT-PCR assay was unable to detect a circulating Latin American strain (DENV-2/NI/BID-V608/2006 due to a sequence variation in the isolate. The Simplexa Dengue RT-PCR test was able to detect and serotype dengue. Based on these findings an updated molecular test algorithm for the virological confirmation of dengue cases was developed and implemented in the Phase 3 efficacy trials.

  19. Brazilian avian metapneumovirus subtypes A and B: experimental infection of broilers and evaluation of vaccine efficacy

    OpenAIRE

    Márcia B. dos Santos; Matheus C. Martini; Helena L. Ferreira; Luciana H.A. da Silva; Paulo A. Fellipe; Fernando R. Spilki; Clarice W. Arns

    2012-01-01

    Santos M.B., Martini M.C., Ferreira H.L., Silva L.H.A., Fellipe P.A., Spilki F.R. & Arns C.W. 2012. Brazilian avian metapneumovirus subtypes A and B: experimental infection of broilers and evaluation of vaccine efficacy. Pesquisa Veterinaria Brasileira 32(12):1257-1262. Laboratorio de Virologia, Instituto de Biologia, Universidade Estadual de Campinas, Rua Monteiro Lobato s/n, Cx. Postal 6109, Campinas, SP 13083-970, Brazil. E-mail: Avian metapneumovirus (aMPV) is a respirator...

  20. Efficacy of a polyvalent immersion vaccine against Flavobacterium psychrophilum and evaluation of immune response to vaccination in rainbow trout fry (Onchorynchus mykiss L.).

    Science.gov (United States)

    Hoare, R; Ngo, T P H; Bartie, K L; Adams, A

    2017-08-18

    Rainbow trout fry syndrome (RTFS) is a disease caused by the Gram-negative bacterium Flavobacterium psychrophilum, responsible for significant economic losses in salmonid aquaculture worldwide. The diversity of F. psychrophilum isolates and the inherent difficulties in vaccinating juvenile fish has hampered the development of a vaccine for RTFS. Disease episodes tend to occur between 10-14 °C with necrotic lesions often seen on the skin surrounding the dorsal fin and tail. At present no commercial vaccines are available for RTFS in the UK, leaving antibiotics as the only course of action to control disease outbreaks. The current work was performed as a pilot study to assess the efficacy of a polyvalent, whole cell vaccine containing formalin-inactivated F. psychrophilum, to induce protective immunity in rainbow trout fry. Duplicate groups of 30 trout (5 g) were immersed in 1 L of the vaccine for 30 s. Samples were taken 4 h, day 2 and 7 post-vaccination (pv) of skin mucus, tissues for histology and gene expression analysis; serum and histology samples were taken 6 weeks pv. A booster vaccination was given at 315 degree days (dd) also by immersion. Challenge was by immersion with a heterologous isolate of F. psychrophilum 630 dd post primary vaccination. The vaccine provided significant protection to the trout fry with a RPS of 84% (p < 0.0001). Detection of increased numbers of IgT positive cells in systemic organs, up-regulation of IgT expression in hind-gut and an increase in total IgT in serum was observed in vaccinated fish; however a functional role of IgT in the observed protection remains to be demonstrated.

  1. A Threat- and Efficacy-Based Framework to Understand Confidence in Vaccines among the Public Health Workforce

    Directory of Open Access Journals (Sweden)

    Lainie Rutkow

    2013-04-01

    Full Text Available The Extended Parallel Process Model (EPPM is an established threat- and efficacy-based behavioral framework for understanding health behaviors in the face of uncertain risk. A growing body of research has applied this model to understand these behaviors among the public health workforce. In this manuscript, we aim to explore the application of this framework to the public health workforce, with a novel focus on their confidence in vaccines and perceptions of vaccine injury compensation mechanisms. We characterize specific connections between EPPM’s threat and efficacy dimensions and relevant vaccine policy frameworks and highlight how these connections can usefully inform training interventions for public health workers to enhance their confidence in these vaccine policy measures.

  2. Flu Vaccine Safety and Pregnancy

    Science.gov (United States)

    ... Influenza Types Seasonal Avian Swine Variant Pandemic Other Flu Vaccine Safety and Pregnancy Questions & Answers Language: English ( ... flu vaccine? Why should pregnant women get a flu shot? Flu is more likely to cause severe ...

  3. Protective efficacy of a live attenuated anti-coccidial vaccine administered to 1-day-old chickens.

    Science.gov (United States)

    Crouch, C F; Andrews, S J; Ward, R G; Francis, M J

    2003-06-01

    The efficacy of a live attenuated anti-coccidial vaccine, Paracox-5, administered to 1-day-old chicks was investigated by assessing protection against changes in weight gain following virulent challenge. Vaccinated birds were challenged independently 28 days later with each of the component species (Eimeria acervulina, Eimeria maxima, Eimeria mitis or Eimeria tenella), and protection was demonstrated against associated reduction in weight gain and lesion formation. In addition, an improvement in bird performance, in terms of feed conversion ratio, was also observed following vaccination. Furthermore, under conditions designed to more closely mimic those in the field and using hatchery spray administration, protection against a mixed virulent challenge introduced by 'seeder birds' was demonstrated evenly across a flock of broiler birds within 21 days after vaccination. These data demonstrate that Paracox-5 vaccine will protect broiler chickens against the adverse effects on performance induced by Eimeria spp.

  4. On the efficacy of malaria DNA vaccination with magnetic gene vectors.

    Science.gov (United States)

    Nawwab Al-Deen, Fatin; Ma, Charles; Xiang, Sue D; Selomulya, Cordelia; Plebanski, Magdalena; Coppel, Ross L

    2013-05-28

    We investigated the efficacy and types of immune responses from plasmid malaria DNA vaccine encoding VR1020-PyMSP119 condensed on the surface of polyethyleneimine (PEI)-coated SPIONs. In vivo mouse studies were done firstly to determine the optimum magnetic vector composition, and then to observe immune responses elicited when magnetic vectors were introduced via different administration routes. Higher serum antibody titers against PyMSP119 were observed with intraperitoneal and intramuscular injections than subcutaneous and intradermal injections. Robust IgG2a and IgG1 responses were observed for intraperitoneal administration, which could be due to the physiology of peritoneum as a major reservoir of macrophages and dendritic cells. Heterologous DNA prime followed by single protein boost vaccination regime also enhanced IgG2a, IgG1, and IgG2b responses, indicating the induction of appropriate memory immunity that can be elicited by protein on recall. These outcomes support the possibility to design superparamagnetic nanoparticle-based DNA vaccines to optimally evoke desired antibody responses, useful for a variety of diseases including malaria. Copyright © 2013 Elsevier B.V. All rights reserved.

  5. Swine Flu -A Comprehensive View

    Science.gov (United States)

    Singh, Vandana; Sood, Meenakshi

    2012-07-01

    The present article is aimed on comprehensive view of Swine flu. It was first isolated from pigs in 1930 in USA. Pandemic caused by H1N1 in 2009 brought it in limelight. Itís a viral respiratory disease caused by viruses that infects pigs, resulting in nasal secretions, barking cough, decreased appetite, and listless behavior. Swine virus consist of eight RNA strands, one strand derived from human flu strains, two from avian (bird) strains, and five from swine strains. Swine flu spreads from infected person to healthy person by inhalation or ingestion of droplets contaminated with virus while sneezing or coughing. Two antiviral agents have been reported to help prevent or reduce the effects of swine flu, flu shot and nasal spray. WHO recommended for pandemic period to prevent its future outbreaks through vaccines or non-vaccines means. Antiviral drugs effective against this virus are Tamiflu and Relenza. Rapid antigen testing (RIDT), DFA testing, viral culture, and molecular testing (RT-PCR) are used for its diagnosis in laboratory

  6. Replacement of the in vivo neutralisation test for efficacy demonstration of tetanus vaccines ad us. vet.

    Science.gov (United States)

    Rosskopf, Ute; Noeske, Kerstin; Werner, Esther

    2005-01-01

    The bacterium Clostridium (C.) tetani is an ubiquitous pathogen. This anaerobic, gram-positive bacterium can form spores and can be found in the whole environment. It enters the body via injuries of the skin and wounds where it releases the neurotoxin "tetanospasmin" (= tetanus toxin). The animals most susceptible to tetanus infection are horses and sheep. Only active immunisation by tetanus vaccine provides effective protection against tetanus intoxication. The marketing authorisation requirements stipulate that efficacy of tetanus vaccines ad us. vet. must be demonstrated in all target animal species via determination of neutralising tetanus serum antitoxin concentrations. The standard method used for this purpose is still the toxin neutralisation test (TNT), as it quantifies the tetanus toxin-neutralising effect of tetanus serum antibodies in vivo. In this test, tetanus toxin is added to dilutions of serum from vaccinated horse and sheep. The serum dilutions are then administered to mice or guinea pigs, which are observed for toxic symptoms. Against the background of animal protection, the goal of one project of the Paul-Ehrlich-Institut (Bundesministerium fuer Bildung und Forschung (Federal Ministry for Education and Research), 0312636) was to establish an alternative to the toxin neutralisation test, enabling the testing of efficacy of tetanus vaccines with serological in vitro methods. For this purpose, a so-called double antigen ELISA (DAE) was established which enables the testing of sera of different species in one assay. In addition, the sera were tested in an indirect ELISA for horses and sheep separately. Altogether, ten groups of horses and eight groups of sheep were immunised with ten animals per group each. The tetanus vaccines comprised almost all products authorised for the German market at the start of the project. 564 horse sera and 257 sheep sera were tested using the two ELISA methods. Some sera were also tested in vivo. The kinetics of

  7. Doxorubicin and paclitaxel enhance the antitumor efficacy of vaccines directed against HER 2/neu in a murine mammary carcinoma model

    International Nuclear Information System (INIS)

    Eralp, Yesim; Wang, Xiaoyan; Wang, Jian-Ping; Maughan, Maureen F; Polo, John M; Lachman, Lawrence B

    2004-01-01

    The purpose of the present study was to determine whether cytotoxic chemotherapeutic agents administered prior to immunotherapy with gene vaccines could augment the efficacy of the vaccines. Mice were injected in the mammary fat pad with an aggressive breast tumor cell line that expresses HER2/neu. The mice were treated 3 days later with a noncurative dose of either doxorubicin or paclitaxel, and the following day with a gene vaccine to HER2/neu. Two more doses of vaccine were given 14 days apart. Two types of gene vaccines were tested: a plasmid vaccine encoding a self-replicating RNA (replicon) of Sindbis virus (SINCP), in which the viral structural proteins were replaced by the gene for neu; and a viral replicon particle derived from an attenuated strain of Venezuelan equine encephalitis virus, containing a replicon RNA in which the Venezuelan equine encephalitis virus structural proteins were replaced by the gene for neu. Neither vaccination alone nor chemotherapy alone significantly reduced the growth of the mammary carcinoma. In contrast, chemotherapy followed by vaccination reduced tumor growth by a small, but significant amount. Antigen-specific CD8 + T lymphocytes were induced by the combined treatment, indicating that the control of tumor growth was most probably due to an immunological mechanism. The results demonstrated that doxorubicin and paclitaxel, commonly used chemotherapeutic agents for the treatment of breast cancer, when used at immunomodulating doses augmented the antitumor efficacy of gene vaccines directed against HER2/neu. The combination of chemotherapeutic agents plus vaccine immunotherapy may induce a tumor-specific immune response that could be beneficial for the adjuvant treatment of patients with minimal residual disease. The regimen warrants further evaluation in a clinical setting

  8. Induction of Robust Immune Responses in Swine by Using a Cocktail of Adenovirus-Vectored African Swine Fever Virus Antigens.

    Science.gov (United States)

    Lokhandwala, Shehnaz; Waghela, Suryakant D; Bray, Jocelyn; Martin, Cameron L; Sangewar, Neha; Charendoff, Chloe; Shetti, Rashmi; Ashley, Clay; Chen, Chang-Hsin; Berghman, Luc R; Mwangi, Duncan; Dominowski, Paul J; Foss, Dennis L; Rai, Sharath; Vora, Shaunak; Gabbert, Lindsay; Burrage, Thomas G; Brake, David; Neilan, John; Mwangi, Waithaka

    2016-11-01

    The African swine fever virus (ASFV) causes a fatal hemorrhagic disease in domestic swine, and at present no treatment or vaccine is available. Natural and gene-deleted, live attenuated strains protect against closely related virulent strains; however, they are yet to be deployed and evaluated in the field to rule out chronic persistence and a potential for reversion to virulence. Previous studies suggest that antibodies play a role in protection, but induction of cytotoxic T lymphocytes (CTLs) could be the key to complete protection. Hence, generation of an efficacious subunit vaccine depends on identification of CTL targets along with a suitable delivery method that will elicit effector CTLs capable of eliminating ASFV-infected host cells and confer long-term protection. To this end, we evaluated the safety and immunogenicity of an adenovirus-vectored ASFV (Ad-ASFV) multiantigen cocktail formulated in two different adjuvants and at two immunizing doses in swine. Immunization with the cocktail rapidly induced unprecedented ASFV antigen-specific antibody and cellular immune responses against all of the antigens. The robust antibody responses underwent rapid isotype switching within 1 week postpriming, steadily increased over a 2-month period, and underwent rapid recall upon boost. Importantly, the primed antibodies strongly recognized the parental ASFV (Georgia 2007/1) by indirect fluorescence antibody (IFA) assay and Western blotting. Significant antigen-specific gamma interferon-positive (IFN-γ + ) responses were detected postpriming and postboosting. Furthermore, this study is the first to demonstrate induction of ASFV antigen-specific CTL responses in commercial swine using Ad-ASFV multiantigens. The relevance of the induced immune responses in regard to protection needs to be evaluated in a challenge study. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  9. Swine Influenza (Swine Flu) in Pigs

    Science.gov (United States)

    ... Address What's this? Submit What's this? Submit Button Influenza Types Seasonal Avian Swine Variant Pandemic Other Key Facts about Swine Influenza (Swine Flu) in Pigs Language: English (US) Español ...

  10. Potential use of a recombinant replication-defective adenovirus vector carrying the C-terminal portion of the P97 adhesin protein as a vaccine against Mycoplasma hyopneumoniae in swine.

    Science.gov (United States)

    Okamba, Faust René; Arella, Maximilien; Music, Nedzad; Jia, Jian Jun; Gottschalk, Marcelo; Gagnon, Carl A

    2010-07-05

    Mycoplasma hyopneumoniae causes severe economic losses to the swine industry worldwide and the prevention of its related disease, enzootic porcine pneumonia, remains a challenge. The P97 adhesin protein of M. hyopneumoniae should be a good candidate for the development of a subunit vaccine because antibodies produced against P97 could prevent the adhesion of the pathogen to the respiratory epithelial cells in vitro. In the present study, a P97 recombinant replication-defective adenovirus (rAdP97c) subunit vaccine efficiency was evaluated in pigs. The rAdP97c vaccine was found to induce both strong P97 specific humoral and cellular immune responses. The rAdP97c vaccinated pigs developed a lower amount of macroscopic lung lesions (18.5 + or - 9.6%) compared to the unvaccinated and challenged animals (45.8 + or - 11.5%). rAdP97c vaccine reduced significantly the severity of inflammatory response and the amount of M. hyopneumoniae in the respiratory tract. Furthermore, the average daily weight gain was slightly improved in the rAdP97c vaccinated pigs (0.672 + or - 0.068 kg/day) compared to the unvaccinated and challenged animals (0.568 + or - 0.104 kg/day). A bacterin-based commercial vaccine (Suvaxyn MH-one) was more efficient to induce a protective immune response than rAdP97c even if it did not evoke a P97 specific immune response. These results suggest that immunodominant antigens other than P97 adhesin are also important in the induction of a protective immune response and should be taken into account in the future development of M. hyopneumoniae subunit vaccines. Copyright 2010 Elsevier Ltd. All rights reserved.

  11. Safety, efficacy, and biomarkers of nivolumab with vaccine in ipilimumab-refractory or -naive melanoma.

    Science.gov (United States)

    Weber, Jeffrey S; Kudchadkar, Ragini Reiney; Yu, Bin; Gallenstein, Donna; Horak, Christine E; Inzunza, H David; Zhao, Xiuhua; Martinez, Alberto J; Wang, Wenshi; Gibney, Geoffrey; Kroeger, Jodi; Eysmans, Cabell; Sarnaik, Amod A; Chen, Y Ann

    2013-12-01

    Nivolumab, a human immunoglobulin G4-blocking antibody against the T-cell programmed death-1 checkpoint protein, has activity against metastatic melanoma. Its safety, clinical efficacy, and correlative biomarkers were assessed with or without a peptide vaccine in ipilimumab-refractory and -naive melanoma. In this phase I study, 90 patients with unresectable stage III or IV melanoma who were ipilimumab naive and had experienced progression after at least one prior therapy (cohorts 1 to 3, 34 patients) or experienced progression after prior ipilimumab (cohorts 4 to 6, 56 patients) received nivolumab at 1, 3, or 10 mg/kg every 2 weeks for 24 weeks, then every 12 weeks for up to 2 years, with or without a multipeptide vaccine. Nivolumab with vaccine was well tolerated and safe at all doses. The RECIST 1.1 response rate for both ipilimumab-refractory and -naive patients was 25%. Median duration of response was not reached at a median of 8.1 months of follow-up. High pretreatment NY-ESO-1 and MART-1-specific CD8(+) T cells were associated with progression of disease. At week 12, increased peripheral-blood T regulatory cells and decreased antigen-specific T cells were associated with progression. PD-L1 tumor staining was associated with responses to nivolumab, but negative staining did not rule out a response. Patients who experienced progression after nivolumab could respond to ipilimumab. In patients with ipilimumab-refractory or -naive melanoma, nivolumab at 3 mg/kg with or without peptide vaccine was well tolerated and induced responses lasting up to 140 weeks. Responses to nivolumab in ipilimumab-refractory patients or to ipilimumab in nivolumab-refractory patients support combination or sequencing of nivolumab and ipilimumab.

  12. Enhanced protective efficacy of a chimeric form of the schistosomiasis vaccine antigen Sm-TSP-2.

    Directory of Open Access Journals (Sweden)

    Mark S Pearson

    Full Text Available The large extracellular loop of the Schistosoma mansoni tetraspanin, Sm-TSP-2, when fused to a thioredoxin partner and formulated with Freund's adjuvants, has been shown to be an efficacious vaccine against murine schistosomiasis. Moreover, Sm-TSP-2 is uniquely recognised by IgG(1 and IgG(3 from putatively resistant individuals resident in S. mansoni endemic areas in Brazil. In the present study, we expressed Sm-TSP-2 at high yield and in soluble form in E. coli without the need for a solubility enhancing fusion partner. We also expressed in E. coli a chimera called Sm-TSP-2/5B, which consisted of Sm-TSP-2 fused to the immunogenic 5B region of the hookworm aspartic protease and vaccine antigen, Na-APR-1. Sm-TSP-2 formulated with alum/CpG showed significant reductions in adult worm and liver egg burdens in two separate murine schistosomiasis challenge studies. Sm-TSP-2/5B afforded significantly greater protection than Sm-TSP-2 alone when both antigens were formulated with alum/CpG. The enhanced protection obtained with the chimeric fusion protein was associated with increased production of anti-Sm-TSP-2 antibodies and IL-4, IL-10 and IFN-γ from spleen cells of vaccinated animals. Sera from 666 individuals from Brazil who were infected with S. mansoni were screened for potentially deleterious IgE responses to Sm-TSP-2. Anti-Sm-TSP-2 IgE to this protein was not detected (also shown previously for Na-APR-1, suggesting that the chimeric antigen Sm-TSP-2/5B could be used to safely and effectively vaccinate people in areas where schistosomes and hookworms are endemic.

  13. Analysis of the evidence on the efficacy and safety of CYD-TDV dengue vaccine and its potential licensing and implementation through Mexico´s Universal Vaccination Program

    Directory of Open Access Journals (Sweden)

    Mauricio Hernández-Ávila

    2016-01-01

    Full Text Available Dengue is a major global public health problem affecting Latin America and Mexico Prevention and control measures, focusing on epidemiological surveillance and vector control, have been partially effective and costly, thus, the development of a vaccine against dengue has created great expectations among health authorities and scientific communities worldwide. The CYD-TDV dengue vaccine produced by Sanofi-Pasteur is the only dengue vaccine evaluated in phase 3 controlled clinical trials. Notwithstanding the significant contribution to the development of a vaccine against dengue, the three phase 3 clinical studies of CYD-TDV and the meta-analysis of the long-term follow up of those studies, have provided evidence that this vaccine exhibited partial vaccine efficacy to protect against virologically confirmed dengue and lead to four considerations: a adequate vaccine efficacy against dengue virus (DENV infections 3 and 4, less vaccine efficacy against DENV 1 and no protection against infection by DENV 2; b decreased vaccine efficacy in dengue seronegative individuals at the beginning of the vaccination; c 83% and 90% protection against hospitalizations and severe forms of dengue, respectively, at 25 months follow-up; and d increased hospitalization for dengue in the vaccinated group, in children under nine years of age at the time of vaccination, detected since the third year of follow-up. The benefit of the CYD-TDV vaccine can be summarized in the protection against infection by DENV 3 and 4, as well as protection for hospitalizations and severe cases in people over nine years, who have had previous dengue infection, working mainly as a booster. In this review we identified elements on efficacy and safety of this vaccine that must be taken into account in the licensing process and potential inclusion in the national vaccination program of Mexico. The available scientific evidence on the CYD-TDV vaccine shows merits, but also leads to relevant

  14. Protein-energy malnutrition alters IgA responses to rotavirus vaccination and infection but does not impair vaccine efficacy in mice.

    Science.gov (United States)

    Maier, Elizabeth A; Weage, Kristina J; Guedes, Marjorie M; Denson, Lee A; McNeal, Monica M; Bernstein, David I; Moore, Sean R

    2013-12-17

    Conflicting evidence links malnutrition to the reduced efficacy of rotavirus vaccines in developing countries, where diarrhea and undernutrition remain leading causes of child deaths. Here, we adapted mouse models of rotavirus vaccination (rhesus rotavirus, RRV), rotavirus infection (EDIM), and protein-energy malnutrition (PEM) to test the hypothesis that undernutrition reduces rotavirus vaccine immunogenicity and efficacy. We randomized wild type Balb/C dams with 3-day-old pups to a control diet (CD) or an isocaloric, multideficient regional basic diet (RBD) that produces PEM. At 3 weeks of age, we weaned CD and RBD pups to their dams' diet and subrandomized weanlings to receive a single dose of either live oral rotavirus vaccine (RRV) or PBS. At 6 weeks of age, we orally challenged all groups with murine rotavirus (EDIM). Serum and stool specimens were collected before and after RRV and EDIM administration to measure viral shedding and antibody responses by ELISA. RBD pups and weanlings exhibited significant failure to thrive compared to age-matched CD mice (Pvaccination induced higher levels of serum anti-RV IgA responses in RBD vs. CD mice (PVaccination protected CD and RBD mice equally against EDIM infection, as measured by viral shedding. In unvaccinated RBD mice, EDIM shedding peaked 1 day earlier (Pvaccination (Pvaccination mitigated stool IgA responses to EDIM more in CD vs. RBD mice (Pvaccination and infection, undernutrition does not impair rotavirus vaccine efficacy nor exacerbate infection in this mouse model of protein-energy malnutrition. Alternative models are needed to elucidate host-pathogen factors undermining rotavirus vaccine effectiveness in high-risk global settings. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

  15. Four year efficacy of prophylactic human papillomavirus quadrivalent vaccine against low grade cervical, vulvar, and vaginal intraepithelial neoplasia and anogenital warts: randomised controlled trial

    DEFF Research Database (Denmark)

    Dillner, Joakim; Kjaer, Susanne K; Wheeler, Cosette M

    2010-01-01

    To evaluate the prophylactic efficacy of the human papillomavirus (HPV) quadrivalent vaccine in preventing low grade cervical, vulvar, and vaginal intraepithelial neoplasias and anogenital warts (condyloma acuminata).......To evaluate the prophylactic efficacy of the human papillomavirus (HPV) quadrivalent vaccine in preventing low grade cervical, vulvar, and vaginal intraepithelial neoplasias and anogenital warts (condyloma acuminata)....

  16. The Type of Growth Medium Affects the Presence of a Mycobacterial Capsule and Is Associated With Differences in Protective Efficacy of BCG Vaccination Against Mycobacterium tuberculosis

    OpenAIRE

    Prados-Rosales, Rafael; Carreño, Leandro J.; Weinrick, Brian; Batista-Gonzalez, Ana; Glatman-Freedman, Aarona; Xu, Jiayong; Chan, John; Jacobs, William R.; Porcelli, Steven A.; Casadevall, Arturo

    2016-01-01

    Background. Bacillus Calmette-Guerin (BCG) vaccine is widely used for the prevention of tuberculosis, despite limited efficacy. Most immunological studies of BCG or Mycobacterium tuberculosis strains grow bacteria in the presence of detergent, which also strips the mycobacterial capsule. The impact of the capsule on vaccine efficacy has not been explored.

  17. Quantifying the Impact of Natural Immunity on Rotavirus Vaccine Efficacy Estimates: A Clinical Trial in Dhaka, Bangladesh (PROVIDE) and a Simulation Study.

    Science.gov (United States)

    Rogawski, Elizabeth T; Platts-Mills, James A; Colgate, E Ross; Haque, Rashidul; Zaman, K; Petri, William A; Kirkpatrick, Beth D

    2018-03-05

    The low efficacy of rotavirus vaccines in clinical trials performed in low-resource settings may be partially explained by acquired immunity from natural exposure, especially in settings with high disease incidence. In a clinical trial of monovalent rotavirus vaccine in Bangladesh, we compared the original per-protocol efficacy estimate to efficacy derived from a recurrent events survival model in which children were considered naturally exposed and potentially immune after their first rotavirus diarrhea (RVD) episode. We then simulated trial cohorts to estimate the expected impact of prior exposure on efficacy estimates for varying rotavirus incidence rates and vaccine efficacies. Accounting for natural immunity increased the per-protocol vaccine efficacy estimate against severe RVD from 63.1% (95% confidence interval [CI], 33.0%-79.7%) to 70.2% (95% CI, 44.5%-84.0%) in the postvaccination period, and original year 2 efficacy was underestimated by 14%. The simulations demonstrated that this expected impact increases linearly with RVD incidence, will be greatest for vaccine efficacies near 50%, and can reach 20% in settings with high incidence and low efficacy. High rotavirus incidence leads to predictably lower vaccine efficacy estimates due to the acquisition of natural immunity in unvaccinated children, and this phenomenon should be considered when comparing efficacy estimates across settings. NCT01375647.

  18. Efficacy and immunogenicity of live-attenuated human rotavirus vaccine in breast-fed and formula-fed European infants.

    Science.gov (United States)

    Vesikari, Timo; Prymula, Roman; Schuster, Volker; Tejedor, Juan-C; Cohen, Robert; Bouckenooghe, Alain; Damaso, Silvia; Han, Htay Htay

    2012-05-01

    Rotavirus is the main cause of severe gastroenteritis and diarrhea in infants and young children less than 5 years of age. Potential impact of breast-feeding on the efficacy and immunogenicity of human rotavirus G1P[8] vaccine was examined in this exploratory analysis. Healthy infants (N = 3994) aged 6-14 weeks who received 2 doses of human rotavirus vaccine/placebo according to a 0-1 or 0-2 month schedule were followed for rotavirus gastroenteritis during 2 epidemic seasons. Rotavirus IgA seroconversion rate (anti-IgA antibody concentration ≥ 20 mIU/mL) and geometric mean concentrations were measured prevaccination and 1-2 months post-dose 2. Vaccine efficacy against any and severe rotavirus gastroenteritis was analyzed according to the infants being breast-fed or exclusively formula-fed at the time of vaccination. Antirotavirus IgA seroconversion rate was 85.5% (95% confidence interval [CI]: 82.4-88.3) in breast-fed and 89.2% (95% CI: 84.2-93) in exclusively formula-fed infants; geometric mean concentrations in the respective groups were 185.8 U/mL (95% CI: 161.4-213.9) and 231.5 U/mL (95% CI: 185.9-288.2). Vaccine efficacy was equally high in breast-fed and exclusively formula-fed children in the first season but fell in breast-fed infants in the second rotavirus season. During the combined 2-year efficacy follow-up period, vaccine efficacy against any rotavirus gastroenteritis was 76.2% (95% CI: 68.7-82.1) and 89.8% (95% CI: 77.6-95.9) and against severe rotavirus gastroenteritis 88.4% (95% CI: 81.6-93) and 98.1% (95% CI: 88.2-100) in the breast-fed and exclusively formula-fed infants, respectively. The difference in immunogenicity of human rotavirus vaccine in breast-fed and exclusively formula-fed infants was small. Vaccine efficacy was equally high in breast-fed and exclusively formula-fed children in the first season. Breast-feeding seemed to reduce slightly the efficacy in the second season.

  19. Oral vaccination of brushtail possums with BCG: Investigation into factors that may influence vaccine efficacy and determination of duration of protection.

    Science.gov (United States)

    Buddle, B M; Aldwell, F E; Keen, D L; Parlane, N A; Hamel, K L; de Lisle, G W

    2006-10-01

    To determine factors that may influence the efficacy of an oral pelleted vaccine containing Mycobacterium bovis bacille Calmette-Guérin (BCG) to induce protection of brushtail possums against tuberculosis. To determine the duration of protective immunity following oral administration of BCG. In Study 1, a group of possums (n=7) was immunised by feeding 10 pellets containing dead Pasteur BCG, followed 15 weeks later with a single pellet of live Pasteur BCG. At that time, four other groups of possums (n=7 per group) were given a single pellet of live Pasteur BCG orally, a single pellet of live Danish BCG orally, 10 pellets of live Pasteur BCG orally, or a subcutaneous injection of live Pasteur BCG. For the oral pelleted vaccines, BCG was formulated into a lipid matrix, and each pellet contained approximately 107 colony forming units (cfu) of BCG, while the vaccine injected subcutaneously contained 106 cfu of BCG. A sixth, non-vaccinated, group (n=7) served as a control. All possums were challenged by the aerosol route with a low dose of virulent M. bovis 7 weeks after vaccination, and killed 7-8 weeks after challenge. Protection against challenge with M. bovis was assessed from pathological and bacteriological findings. In Study 2, lipid-formulated live Danish BCG was administered orally to three groups of possums (10-11 per group), and these possums were challenged with virulent M. bovis 8, 29 or 54 weeks later. The possums were killed 7 weeks after challenge, to assess protection in comparison to a non-vaccinated group. The results from Study 1 showed that vaccine efficacy was not adversely affected by feeding dead BCG prior to live BCG. Feeding 10 vaccine pellets induced a level of protection similar to feeding a single pellet. Protection was similar when feeding possums a single pellet containing the Pasteur or Danish strains of BCG. All vaccinated groups had significantly reduced pathological changes or bacterial counts when compared to the non-vaccinated group

  20. A systematic review of anti-rotavirus serum IgA antibody titer as a potential correlate of rotavirus vaccine efficacy.

    Science.gov (United States)

    Patel, Manish; Glass, Roger I; Jiang, Baoming; Santosham, Mathuram; Lopman, Ben; Parashar, Umesh

    2013-07-15

    Identifying an immunological correlate of protection for rotavirus vaccines (Rotarix [RV1] and RotaTeq [RV5]) would substantially facilitate testing of interventions for improving efficacy in developing countries and evaluating additional candidate rotavirus vaccines. We accessed PubMed and ClinicalTrials.gov to identify immunogenicity and efficacy trials for RV1 and RV5 to correlate anti-rotavirus serum immunoglobulin A (IgA) antibody titers vs efficacy in regions stratified by all-cause under-5 mortality rates (u5MR). We established a cutoff point for IgA geometric mean concentration or titer (GMC) that predicted lower efficacy and calculated pooled vaccine efficacy among countries with high vs low IgA titers. We observed an inverse correlation between u5MR and IgA titers for RV1 (r(2) = 0.72; P efficacy and IgA titers for both vaccines (r(2) = 0.56; P = .005). Postimmunization anti-rotavirus IgA GMC vaccine efficacy. Efficacy during first 2 years of life was significantly lower among countries with IgA GMC 90 (85%; 95% CI, 82-88). We observed a significant correlation between IgA titers and rotavirus vaccine efficacy and hypothesize that a critical level of IgA antibody titer is associated with a sufficient level of sustained protection after rotavirus vaccination.

  1. Pre- and post-exposure safety and efficacy of attenuated rabies virus vaccines are enhanced by their expression of IFNγ

    International Nuclear Information System (INIS)

    Barkhouse, Darryll A.; Faber, Milosz; Hooper, D. Craig

    2015-01-01

    Consistent with evidence of a strong correlation between interferon gamma (IFNγ) production and rabies virus (RABV) clearance from the CNS, we recently demonstrated that engineering a pathogenic RABV to express IFNγ highly attenuates the virus. Reasoning that IFNγ expression by RABV vaccines would enhance their safety and efficacy, we reverse-engineered two proven vaccine vectors, GAS and GASGAS, to express murine IFNγ. Mortality and morbidity were monitored during suckling mice infection, immunize/challenge experiments and mixed intracranial infections. We demonstrate that GASγ and GASγGAS are significantly attenuated in suckling mice compared to the GASGAS vaccine. GASγ better protects mice from lethal DRV4 RABV infection in both pre- and post-exposure experiments compared to GASGAS. Finally, GASγGAS reduces post-infection neurological sequelae, compared to control, during mixed intracranial infection with DRV4. These data show IFNγ expression by a vaccine vector can enhance its safety while increasing its efficacy as pre- and post-exposure treatment. - Highlights: • IFNγ expression improves attenuated rabies virus safety and immunogenicity. • IFNγ expression is safer and more immunogenic than doubling glycoprotein expression. • Co-infection with IFNγ-expressing RABV prevents wild-type rabies virus lethality. • Vaccine safety and efficacy is additive for IFNγ and double glycoprotein expression

  2. Pre- and post-exposure safety and efficacy of attenuated rabies virus vaccines are enhanced by their expression of IFNγ

    Energy Technology Data Exchange (ETDEWEB)

    Barkhouse, Darryll A. [Department of Cancer Biology, 1020 Locust St., Jefferson Alumni Hall, Room 454, Philadelphia, PA 19107 (United States); Center for Neurovirology 1020 Locust St., Jefferson Alumni Hall, Room 454, Philadelphia, PA 19107 (United States); Faber, Milosz [Center for Neurovirology 1020 Locust St., Jefferson Alumni Hall, Room 454, Philadelphia, PA 19107 (United States); Department of Microbiology and Immunology 1020 Locust St., Jefferson Alumni Hall, Room 465, Philadelphia, PA 19107 (United States); Hooper, D. Craig, E-mail: douglas.hooper@jefferson.edu [Department of Cancer Biology, 1020 Locust St., Jefferson Alumni Hall, Room 454, Philadelphia, PA 19107 (United States); Department of Neurological Surgery, 1020 Locust St., Jefferson Alumni Hall, Room 454, Philadelphia, PA 19107 (United States); Center for Neurovirology 1020 Locust St., Jefferson Alumni Hall, Room 454, Philadelphia, PA 19107 (United States)

    2015-01-01

    Consistent with evidence of a strong correlation between interferon gamma (IFNγ) production and rabies virus (RABV) clearance from the CNS, we recently demonstrated that engineering a pathogenic RABV to express IFNγ highly attenuates the virus. Reasoning that IFNγ expression by RABV vaccines would enhance their safety and efficacy, we reverse-engineered two proven vaccine vectors, GAS and GASGAS, to express murine IFNγ. Mortality and morbidity were monitored during suckling mice infection, immunize/challenge experiments and mixed intracranial infections. We demonstrate that GASγ and GASγGAS are significantly attenuated in suckling mice compared to the GASGAS vaccine. GASγ better protects mice from lethal DRV4 RABV infection in both pre- and post-exposure experiments compared to GASGAS. Finally, GASγGAS reduces post-infection neurological sequelae, compared to control, during mixed intracranial infection with DRV4. These data show IFNγ expression by a vaccine vector can enhance its safety while increasing its efficacy as pre- and post-exposure treatment. - Highlights: • IFNγ expression improves attenuated rabies virus safety and immunogenicity. • IFNγ expression is safer and more immunogenic than doubling glycoprotein expression. • Co-infection with IFNγ-expressing RABV prevents wild-type rabies virus lethality. • Vaccine safety and efficacy is additive for IFNγ and double glycoprotein expression.

  3. SieveSifter: a web-based tool for visualizing the sieve analyses of HIV-1 vaccine efficacy trials.

    Science.gov (United States)

    Fiore-Gartland, Andrew; Kullman, Nicholas; deCamp, Allan C; Clenaghan, Graham; Yang, Wayne; Magaret, Craig A; Edlefsen, Paul T; Gilbert, Peter B

    2017-08-01

    Analysis of HIV-1 virions from participants infected in a randomized controlled preventive HIV-1 vaccine efficacy trial can help elucidate mechanisms of partial protection. By comparing the genetic sequence of viruses from vaccine and placebo recipients to the sequence of the vaccine itself, a technique called 'sieve analysis', one can identify functional specificities of vaccine-induced immune responses. We have created an interactive web-based visualization and data access tool for exploring the results of sieve analyses performed on four major preventive HIV-1 vaccine efficacy trials: (i) the HIV Vaccine Trial Network (HVTN) 502/Step trial, (ii) the RV144/Thai trial, (iii) the HVTN 503/Phambili trial and (iv) the HVTN 505 trial. The tool acts simultaneously as a platform for rapid reinterpretation of sieve effects and as a portal for organizing and sharing the viral sequence data. Access to these valuable datasets also enables the development of novel methodology for future sieve analyses. Visualization: http://sieve.fredhutch.org/viz . Source code: https://github.com/nkullman/SIEVE . Data API: http://sieve.fredhutch.org/data . agartlan@fredhutch.org. © The Author(s) 2017. Published by Oxford University Press.

  4. Subunit Vaccine Preparation of Bovine Rotavirus and Its Efficacy in Mice.

    Science.gov (United States)

    Suocheng, Wei; Tuanjie, Che; Changjun, Song; Fengling, Tian; Zhongren, Ma

    2015-09-01

    Rotaviruses (RV) are important viral diarrheal agents in calves. Vaccination is an optimum measure to prevent bovine rotaviruses (BRV) infection. However, little research on BRV VP7 vaccine has been done and currently there is no BRV vaccine. To prepare a subunit vaccine of BRV and investigate its efficacy. Total RNA was extracted from MA104 cells infected with bovine rotavirus (BRV) strain GSB01. BRV VP7 gene was amplified using real time fluorescence quantitative PCR (qPCR). The pEASY-T3-VP7 plasmid was digested using HindⅢ and BamHI restriction endonucleases, then recombined into the prokaryotic expression vector pET32a. The pET32a-VP7 and pET32a-VP7-LTB (heat-labile enterotoxin B subunit) were transformed into BL21 (DE3) competent cells of Escherichia coli, respectively, and induced with IPTG, then analyzed using SDS-PAGE. Sixty mice were randomly divided into three groups (n=20). Group A mice was used as His-tag control and mice in group B and C were inoculated with pET32a-VP7 and pET32a-VP7-LTB, respectively. VP7 IgG antibody titers and protection efficiency of pET32a-VP7-LTB were further determined in neonatal mice challenged with GSB01 BRV strain. SDS-PAGE analysis showed that the pET32a-VP7 was highly expressed in the BL21 (DE3) cells. PET32a-VP7 and pET32a-VP7-LTB protein could promote VP7 IgG antibody titer(8.33×103 vs. 17.26×103)in mice. Immunization protection ratios of pET32a-VP7 and pET32a-VP7-LTB proteins in the neonatal mice were 86.4% and 91.7%, respectively. The fusion protein of pET32a-VP7-LTB had excellent immunogenicity and protected mice from BRV infection. Our findings can be used for further developing of a high-efficiency subunit vaccine of BRV.

  5. Protective efficacy of standard Edmonston-Zagreb measles vaccination in infants aged 4.5 months: interim analysis of a randomised clinical trial

    DEFF Research Database (Denmark)

    Martins, C.L.; Garly, May-Lill; Bale, C.

    2008-01-01

    -Bissau. Intervention Measles vaccination using standard titre Edmonston-Zagreb vaccine at 4.5 months of age. Main outcome measures Vaccine efficacy against measles infection, admission to hospital for measles, and measles mortality before standard vaccination at 9 months of age. Results 28% of the children tested at 4...... children developed measles; 19% of unvaccinated children had measles before 9 months of age. The monthly incidence of measles among the 441 children enrolled in the treatment arm was 0.7% and among the 892 enrolled in the control arm was 3.1%. Early vaccination with the Edmonston-Zagreb measles vaccine...... against measles may be low and severe outbreaks of measles can occur in infants before the recommended age of vaccination at 9 months. Outbreaks of measles may be curtailed by measles vaccination using the Edmonston-Zagreb vaccine as early as 4.5 months of age. Trial registration Clinical Trials NCT...

  6. Efficacy and Duration of Immunity after Yellow Fever Vaccination: Systematic Review on the Need for a Booster Every 10 Years

    Science.gov (United States)

    Gotuzzo, Eduardo; Yactayo, Sergio; Córdova, Erika

    2013-01-01

    Current regulations stipulate a yellow fever (YF) booster every 10 years. We conducted a systematic review of the protective efficacy and duration of immunity of YF vaccine in residents of disease-endemic areas and in travelers to assess the need for a booster in these two settings and in selected populations (human immunodeficiency virus–infected persons, infants, children, pregnant women, and severely malnourished persons). Thirty-six studies and 22 reports were included. We identified 12 studies of immunogenicity, 8 of duration of immunity, 8 of vaccine response in infants and children, 7 of human-immunodeficiency virus–infected persons, 2 of pregnant women, and 1 of severely malnourished children. Based on currently available data, a single dose of YF vaccine is highly immunogenic and confers sustained life-long protective immunity against YF. Therefore, a booster dose of YF vaccine is not needed. Special considerations for selected populations are detailed. PMID:24006295

  7. Efficacy of an inactivated feline panleucopenia virus vaccine against a canine parvovirus isolated from a domestic cat.

    Science.gov (United States)

    Gamoh, K; Senda, M; Inoue, Y; Itoh, O

    2005-09-03

    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.

  8. Neutralizing Antibody Response and Efficacy of Novel Recombinant Tetravalent Dengue DNA Vaccine Comprising Envelope Domain III in Mice

    Directory of Open Access Journals (Sweden)

    Ajit Kulkarni

    2017-03-01

    Full Text Available Background: Dengue is a global arboviral threat to humans; causing 390 million infections per year. The availability of safe and effective tetravalent dengue vaccine is a global requirement to prevent epidemics, morbidity, and mortality associated with it. Methods: Five experimental groups (6 mice per group each of 5-week-old BALB/c mice were immunized with vaccine and placebo (empty plasmid (100 µg, i.m. on days 0, 14 and 28. Among these, four groups (one group per serotype of each were subsequently challenged 3 weeks after the last boost with dengue virus (DENV serotypes 1-4 (100 LD50, 20 µl intracerebrally to determine vaccine efficacy. The fifth group of each was used as a control. The PBS immunized group was used as mock control. Serum samples were collected before and after subsequent immunizations. EDIII fusion protein expression was determined by Western blot. Total protein concentration was measured by Bradford assay. Neutralizing antibodies were assessed by TCID50-CPE inhibition assay. Statistical analysis was performed using Stata/IC 10.1 software for Windows. One-way repeated measures ANOVA and Mann-Whitney test were used for neutralizing antibody analysis and vaccine efficacy, respectively. Results: The recombinant EDIII fusion protein was expressed adequately in transfected 293T cells. Total protein concentration was almost 3 times more than the control. Vaccine candidate induced neutralizing antibodies against all four DENV serotypes with a notable increase after subsequent boosters. Vaccine efficacy was 83.3% (DENV-1, -3, -4 and 50% (DENV-2. Conclusion: Our results suggest that vaccine is immunogenic and protective; however, further studies are required to improve the immunogenicity particularly against DENV-2.

  9. Safety, immunogenicity, and protective efficacy of two doses of RIX4414 live attenuated human rotavirus vaccine in healthy infants.

    Science.gov (United States)

    Araujo, Eliete C; Clemens, Sue Ann C; Oliveira, Consuelo S; Justino, Maria Cleonice A; Rubio, Pilar; Gabbay, Yvone B; da Silva, Veronilce B; Mascarenhas, Joana D P; Noronha, Vânia L; Clemens, Ralf; Gusmão, Rosa Helena P; Sanchez, Nervo; Monteiro, Talita Antônia F; Linhares, Alexandre C

    2007-01-01

    To determine the safety, immunogenicity and efficacy of two doses of rotavirus vaccine in healthy Brazilian infants. A randomized, multicenter, double-blind, placebo-controlled trial was conducted in Brazil, Mexico and Venezuela. Infants received two oral doses of vaccine or placebo at 2 and 4 months of age, concurrently with routine immunizations, except for oral poliomyelitis vaccine (OPV). This paper reports results from Belém, Brazil, where the number of subjects per group and the viral vaccine titers were: 194 (10(4.7) focus forming units - FFU), 196 (10(5.2) FFU), 194 (10(5.8) FFU) and 194 (placebo). Anti-rotavirus (anti-RV) antibody response was assessed in 307 subjects. Clinical severity of gastroenteritis episodes was measured using a 20-point scoring system with a score of >or= 11 defined as severe GE. The rates of solicited general symptoms were similar in vaccine and placebo recipients. At 2 months after the second dose, a serum IgA response to RV occurred in 54.7 to 74.4% of vaccinees. No interference was seen in the immunogenicity of routine vaccines. Vaccine efficacy against any rotavirus gastroenteritis (RVGE) was 63.5% (95%CI 20.8-84.4) for the highest concentration (10(5.8) FFU). Efficacy was 81.5% (95%CI 44.5-95.4) against severe RVGE. At its highest concentration (10(5.8) FFU), RIX4414 provided 79.8% (95%CI 26.4-96.3) protection against severe RVGE by G9 strain. RIX4414 was highly immunogenic with a low reactogenicity profile and did not interfere with seroresponse to diphtheria, tetanus, pertussis, hepatitis B and Hib antigens. Two doses of RIX4414 provided significant protection against severe GE caused by RV.

  10. An experimental Toxoplasma gondii dose response challenge model to study therapeutic or vaccine efficacy in cats.

    Directory of Open Access Journals (Sweden)

    Jan B W J Cornelissen

    Full Text Available High numbers of Toxoplasma gondii oocysts in the environment are a risk factor to humans. The environmental contamination might be reduced by vaccinating the definitive host, cats. An experimental challenge model is necessary to quantitatively assess the efficacy of a vaccine or drug treatment. Previous studies have indicated that bradyzoites are highly infectious for cats. To infect cats, tissue cysts were isolated from the brains of mice infected with oocysts of T. gondii M4 strain, and bradyzoites were released by pepsin digestion. Free bradyzoites were counted and graded doses (1000, 100, 50, 10, and 250 intact tissue cysts were inoculated orally into three cats each. Oocysts shed by these five groups of cats were collected from faeces by flotation techniques, counted microscopically and estimated by real time PCR. Additionally, the number of T. gondii in heart, tongue and brains were estimated, and serology for anti T. gondii antibodies was performed. A Beta-Poisson dose-response model was used to estimate the infectivity of single bradyzoites and linear regression was used to determine the relation between inoculated dose and numbers of oocyst shed. We found that real time PCR was more sensitive than microscopic detection of oocysts, and oocysts were detected by PCR in faeces of cats fed 10 bradyzoites but by microscopic examination. Real time PCR may only detect fragments of T. gondii DNA without the presence of oocysts in low doses. Prevalence of tissue cysts of T. gondii in tongue, heart and brains, and anti T. gondii antibody concentrations were all found to depend on the inoculated bradyzoite dose. The combination of the experimental challenge model and the dose response analysis provides a suitable reference for quantifying the potential reduction in human health risk due to a treatment of domestic cats by vaccination or by therapeutic drug application.

  11. Yeast-recombinant hepatitis B vaccine: efficacy with hepatitis B immune globulin in prevention of perinatal hepatitis B virus transmission

    International Nuclear Information System (INIS)

    Stevens, C.E.; Taylor, P.E.; Tong, M.J.; Toy, P.T.; Vyas, G.N.; Nair, P.V.; Weissman, J.Y.; Krugman, S.

    1987-01-01

    A yeast-recombinant hepatitis B vaccine was licensed recently by the Food and Drug administration and is now available. To assess the efficacy of the yeast-recombinant vaccine, the authors administered the vaccine in combination with hepatitis B immune globulin to high-risk newborns. If infants whose mothers were positive for both hepatitis B surface antigen and the e antigen receive no immunoprophylaxis, 70% to 90% become infected with the virus, and almost all become chronic carriers. Among infants in this study who received hepatitis B immune globulin at birth and three 5- + g doses of yeast-recombinant hepatitis B vaccine, only 4.8% became chronic carriers, a better than 90% level of protection and a rate that is comparable with that seen with immune globulin and plasma-derived hepatitis B vaccine. Hepatitis surface antigen and antibodies were detected by radioimmunoassay. These data suggest that, in this high-risk setting, the yeast-recombinant vaccine is as effective as the plasma-derived vaccine in preventing hepatitis B virus infection and the chronic carrier state

  12. Efficacy and Safety of Vaccination in Pediatric Patients with Systemic Inflammatory Rheumatic Diseases: a systematic review of the literature

    Directory of Open Access Journals (Sweden)

    Sandra Sousa

    2017-01-01

    Full Text Available Introduction: Children and adolescents with systemic rheumatic diseases have an increased risk of infections. Although some infections are vaccine-preventable, immunization among patients with juvenile rheumatic diseases is suboptimal, partly due to some doubts that still persist regarding its efficacy and safety in this patient population. Objectives: To review the available evidence regarding the immunological response and the safety of vaccination in children and adolescents with systemic inflammatory rheumatic diseases (SIRD. Methods: A systematic review of the current literature until December 2014 using MEDLINE, EMBASE and abstracts from the American College of Rheumatology and European League Against Rheumatism congresses (2011-2014, complemented by hand search was performed. Eligible studies were identified and efficacy (seroprotection and/or seroconversion and safety (reactions to vaccine and relapse of rheumatic disease outcomes were extracted and summarized according to the type of vaccine. Results: Twenty-eight articles concerning vaccination in pediatric patients with SIRDs were found, that included almost 2100 children and adolescents, comprising nearly all standard vaccinations of the recommended immunization schedule. Children with SIRDs generally achieved seroprotection and seroconversion; nevertheless, the antibody levels were often lower when compared with healthy children. Glucocorticoids and conventional disease-modifying anti-rheumatic drugs do not seem to significantly hamper the immune responses, whereas TNF inhibitors may reduce antibody production, particularly in response to pneumococcal conjugate, influenza, meningococcal C and hepatitis A vaccine. There were no serious adverse events, nor evidence of a relevant worsening of the underlying rheumatic disease. Concerning live attenuated vaccines, the evidence is scarce, but no episodes of overt disease were reported, even in patients under biological therapy

  13. Efficacy and Safety of Vaccination in Pediatric Patients with Systemic Inflammatory Rheumatic Diseases: a systematic review of the literature.

    Science.gov (United States)

    Sousa, Sandra; Duarte, Ana Catarina; Cordeiro, Inês; Ferreira, Joana; Gonçalves, Maria João; Meirinhos, Tiago; Rocha, Teresa Martins; Romão, Vasco C; Santos, Maria José

    2017-01-01

    Children and adolescents with systemic rheumatic diseases have an increased risk of infections. Although some infections are vaccine-preventable, immunization among patients with juvenile rheumatic diseases is suboptimal, partly due to some doubts that still persist regarding its efficacy and safety in this patient population. To review the available evidence regarding the immunological response and the safety of vaccination in children and adolescents with systemic inflammatory rheumatic diseases (SIRD). A systematic review of the current literature until December 2014 using MEDLINE, EMBASE and abstracts from the American College of Rheumatology and European League Against Rheumatism congresses (2011-2014), complemented by hand search was performed. Eligible studies were identified and efficacy (seroprotection and/or seroconversion) and safety (reactions to vaccine and relapse of rheumatic disease) outcomes were extracted and summarized according to the type of vaccine. Twenty-eight articles concerning vaccination in pediatric patients with SIRDs were found, that included almost 2100 children and adolescents, comprising nearly all standard vaccinations of the recommended immunization schedule. Children with SIRDs generally achieved seroprotection and seroconversion; nevertheless, the antibody levels were often lower when compared with healthy children. Glucocorticoids and conventional disease-modifying anti-rheumatic drugs do not seem to significantly hamper the immune responses, whereas TNF inhibitors may reduce antibody production, particularly in response to pneumococcal conjugate, influenza, meningococcal C and hepatitis A vaccine. There were no serious adverse events, nor evidence of a relevant worsening of the underlying rheumatic disease. Concerning live attenuated vaccines, the evidence is scarce, but no episodes of overt disease were reported, even in patients under biological therapy. Existing literature demonstrates that vaccines are generally well

  14. Reversion to virulence and efficacy of an attenuated canarypox vaccine in Hawai'i 'Amakihi (Hemignathus Virens)

    Science.gov (United States)

    Atkinson, Carter T.; Wiegand, Kimberly C.; Triglia, Dennis; Jarvi, Susan I.

    2012-01-01

    Vaccines may be effective tools for protecting small populations of highly susceptible endangered, captive-reared, or translocated Hawaiian honeycreepers from introduced Avipoxvirus, but their efficacy has not been evaluated. An attenuated Canarypox vaccine that is genetically similar to one of two passerine Avipoxvirus isolates from Hawai‘i and distinct from Fowlpox was tested to evaluate whether Hawai‘i ‘Amakihi (Hemignathus virens) can be protected from wild isolates of Avipoxvirus from the Hawaiian Islands. Thirty-one (31) Hawai‘i ‘Amakihi were collected from high-elevation habitats on Mauna Kea Volcano, where pox transmission is rare, and randomly divided into two groups. One group was vaccinated with Poximune C®, whereas the other group received a sham vaccination with sterile water. Four of 15 (27%) vaccinated birds developed life-threatening disseminated lesions or lesions of unusually long duration, whereas one bird never developed a vaccine-associated lesion or “take.” After vaccine lesions healed, vaccinated birds were randomly divided into three groups of five and challenged with either a wild isolate of Fowlpox (FP) from Hawai‘i, a Hawai‘i ‘Amakihi isolate of a Canarypox-like virus (PV1), or a Hawai‘i ‘Amakihi isolate of a related, but distinct, passerine Avipoxvirus (PV2). Similarly, three random groups of five unvaccinated ‘Amakihi were challenged with the same virus isolates. Vaccinated and unvaccinated ‘Amakihi challenged with FP had transient infections with no clinical signs of infection. Mortality in vaccinated ‘Amakihi challenged with PV1 and PV2 ranged from 0% (0/5) for PV1 to 60% (3/5) for PV2. Mortality in unvaccinated ‘Amakihi ranged from 40% (2/5) for PV1 to 100% (5/5) for PV2. Although the vaccine provided some protection against PV1, both potential for vaccine reversion and low efficacy against PV2 preclude its use in captive or wild honeycreepers.

  15. Efficacy of RTS,S/AS01E Vaccine against Malaria in Children 5 to 17 Months of Age

    Science.gov (United States)

    Bejon, Philip; Lusingu, John; Olotu, Ally; Leach, Amanda; Lievens, Marc; Vekemans, Johan; Mshamu, Salum; Lang, Trudie; Gould, Jayne; Dubois, Marie-Claude; Demoitié, Marie-Ange; Stallaert, Jean-Francois; Vansadia, Preeti; Carter, Terrell; Njuguna, Patricia; Awuondo, Ken O.; Malabeja, Anangisye; Abdul, Omar; Gesase, Samwel; Mturi, Neema; Drakeley, Chris J.; Savarese, Barbara; Villafana, Tonya; Ballou, W. Ripley; Cohen, Joe; Riley, Eleanor M.; Lemnge, Martha M.; Marsh, Kevin; von Seidlein, Lorenz

    2009-01-01

    BACKGROUND Plasmodium falciparum malaria is a pressing global health problem. A previous study of the malaria vaccine RTS,S (which targets the circumsporozoite protein), given with an adjuvant system (AS02A), showed a 30% rate of protection against clinical malaria in children 1 to 4 years of age. We evaluated the efficacy of RTS,S given with a more immunogenic adjuvant system (AS01E) in children 5 to 17 months of age, a target population for vaccine licensure. METHODS We conducted a double-blind, randomized trial of RTS,S/AS01E vaccine as compared with rabies vaccine in children in Kilifi, Kenya, and Korogwe, Tanzania. The primary end point was fever with a falciparum parasitemia density of more than 2500 parasites per microliter, and the mean duration of follow-up was 7.9 months (range, 4.5 to 10.5). RESULTS A total of 894 children were randomly assigned to receive the RTS,S/AS01E vaccine or the control (rabies) vaccine. Among the 809 children who completed the study procedures according to the protocol, the cumulative number in whom clinical malaria developed was 32 of 402 assigned to receive RTS,S/AS01E and 66 of 407 assigned to receive the rabies vaccine; the adjusted efficacy rate for RTS,S/AS01E was 53% (95% confidence interval [CI], 28 to 69; P<0.001) on the basis of Cox regression. Overall, there were 38 episodes of clinical malaria among recipients of RTS,S/AS01E, as compared with 86 episodes among recipients of the rabies vaccine, with an adjusted rate of efficacy against all malarial episodes of 56% (95% CI, 31 to 72; P<0.001). All 894 children were included in the intention-to-treat analysis, which showed an unadjusted efficacy rate of 49% (95% CI, 26 to 65; P<0.001). There were fewer serious adverse events among recipients of RTS,S/AS01E, and this reduction was not only due to a difference in the number of admissions directly attributable to malaria. CONCLUSIONS RTS,S/AS01E shows promise as a candidate malaria vaccine. (ClinicalTrials.gov number, NCT

  16. Swine flu

    Directory of Open Access Journals (Sweden)

    Manish Sinha

    Full Text Available Summary: The recent outbreak of human infection with a novel Swine-Origin Influenza A (H1N1 virus is spreading rapidly through sustained human-to-human transmission in multiple countries. Human-to-human transmission occurs by inhalation of infectious droplets and droplet nuclei, and by direct contact, which is facilitated by air and land travel and social gatherings. The most frequently reported symptoms are fever, cough, myalgia, and sore throat. Detailed contact and travel histories and knowledge of viral activity in community are essential for prompt case detection by the health personnel. Real-time Reverse Transcriptase-Polymerase Chain Reaction analysis of throat swabs or lower respiratory samples is a sensitive means of diagnosis. Use of oral oseltamivir may be warranted for the treatment of severe illness. Keywords: Swine influenza, H1N1, Swine flu, Oseltamivir

  17. Molecular characterization of African swine fever virus in apparently ...

    African Journals Online (AJOL)

    African swine fever (ASF) is a highly lethal and economically significant disease of domestic pigs in Uganda where outbreaks regularly occur. There is neither a vaccine nor treatment available for ASF control. Twenty two African swine fever virus (ASFV) genotypes (I - XXII) have been identified based on partial sequencing ...

  18. Immune responses of bison and efficacy after booster vaccination with Brucella abortus strain RB51

    Science.gov (United States)

    Thirty-one bison heifers were randomly assigned to saline (control; n=7) or single vaccination (n=24) with 1010 CFU of B. abortus strain RB51 (RB51). Some vaccinated bison were randomly selected for booster vaccination with 10**10 CFU of RB51 at 11 months after initial vaccination (n=16). When comp...

  19. Efficacy and effectiveness of an rVSV-vectored vaccine expressing Ebola surface glycoprotein: interim results from the Guinea ring vaccination cluster-randomised trial.

    Science.gov (United States)

    Henao-Restrepo, Ana Maria; Longini, Ira M; Egger, Matthias; Dean, Natalie E; Edmunds, W John; Camacho, Anton; Carroll, Miles W; Doumbia, Moussa; Draguez, Bertrand; Duraffour, Sophie; Enwere, Godwin; Grais, Rebecca; Gunther, Stephan; Hossmann, Stefanie; Kondé, Mandy Kader; Kone, Souleymane; Kuisma, Eeva; Levine, Myron M; Mandal, Sema; Norheim, Gunnstein; Riveros, Ximena; Soumah, Aboubacar; Trelle, Sven; Vicari, Andrea S; Watson, Conall H; Kéïta, Sakoba; Kieny, Marie Paule; Røttingen, John-Arne

    2015-08-29

    these clusters (4123 people) were randomly assigned to immediate vaccination with rVSV-ZEBOV, and 42 clusters (3528 people) were randomly assigned to delayed vaccination with rVSV-ZEBOV. In the immediate vaccination group, there were no cases of Ebola virus disease with symptom onset at least 10 days after randomisation, whereas in the delayed vaccination group there were 16 cases of Ebola virus disease from seven clusters, showing a vaccine efficacy of 100% (95% CI 74·7-100·0; p=0·0036). No new cases of Ebola virus disease were diagnosed in vaccinees from the immediate or delayed groups from 6 days post-vaccination. At the cluster level, with the inclusion of all eligible adults, vaccine effectiveness was 75·1% (95% CI -7·1 to 94·2; p=0·1791), and 76·3% (95% CI -15·5 to 95·1; p=0·3351) with the inclusion of everyone (eligible or not eligible for vaccination). 43 serious adverse events were reported; one serious adverse event was judged to be causally related to vaccination (a febrile episode in a vaccinated participant, which resolved without sequelae). Assessment of serious adverse events is ongoing. The results of this interim analysis indicate that rVSV-ZEBOV might be highly efficacious and safe in preventing Ebola virus disease, and is most likely effective at the population level when delivered during an Ebola virus disease outbreak via a ring vaccination strategy. WHO, with support from the Wellcome Trust (UK); Médecins Sans Frontières; the Norwegian Ministry of Foreign Affairs through the Research Council of Norway; and the Canadian Government through the Public Health Agency of Canada, Canadian Institutes of Health Research, International Development Research Centre, and Department of Foreign Affairs, Trade and Development. Copyright © 2015 World Health Organization. Published by Elsevier Ltd/Inc/BV. All rights reserved. Published by Elsevier Ltd.. All rights reserved.

  20. A Phylogeny-Based Global Nomenclature System and Automated Annotation Tool for H1 Hemagglutinin Genes from Swine Influenza A Viruses

    Science.gov (United States)

    Macken, Catherine A.; Lewis, Nicola S.; Van Reeth, Kristien; Brown, Ian H.; Swenson, Sabrina L.; Simon, Gaëlle; Saito, Takehiko; Berhane, Yohannes; Ciacci-Zanella, Janice; Pereda, Ariel; Davis, C. Todd; Donis, Ruben O.; Webby, Richard J.

    2016-01-01

    in vaccine antigen selection and allows for inferences about vaccine efficacy. Previous reporting of H1 virus HA in swine relied on colloquial names, frequently with incriminating and stigmatizing geographic toponyms, making comparisons between studies challenging. To overcome this, we developed an adaptable nomenclature using measurable criteria for historical and contemporary evolutionary patterns of H1 global swine IAVs. We also developed a web-accessible tool that classifies viruses according to this nomenclature. This classification system will aid agricultural production and pandemic preparedness through the identification of important changes in swine IAVs and provides terminology enabling discussion of swine IAVs in a common context among animal and human health initiatives. PMID:27981236

  1. THE COMPARISON OF INFLUENZA VACCINE EFFICACY ON RESPIRATORY DISEASE AMONG IRANIAN PILGRIMS IN THE 2003 AND 2004 SEASONS

    Directory of Open Access Journals (Sweden)

    M. Razavi

    2005-07-01

    Full Text Available Prolonged cough occurs in a large proportion of the 2 million pilgrims who participate in the annual Hajj in Saudi Arabia. There is no unique cause for pilgrims’ respiratory involvement, but several studies suggest a high incidence of influenza as a cause of the disease. To determine influenza vaccine efficacy against respiratory disease in pilgrims, we conducted two similar cohort studies on 51100 Iranian pilgrims who had participated in the annual Hajj in the years 2003 and 2004. We calculated vaccine efficacy in these two years with the use of “1- odd’s ratio” formula and compared the results. The vaccine efficacy for prevention of influenza like illness in the year 2003 was 51% but the vaccine was not efficient in the year 2004. It was concluded that etiologic agents other than influenza virus should be considered as the cause of respiratory disease in Hajj. Bacterial infections superimposed on chronic respiratory diseases, and allergic or toxic conditions are suggested caourses for more investigation.

  2. Novel Ordered Stepped-Wedge Cluster Trial Designs for Detecting Ebola Vaccine Efficacy Using a Spatially Structured Mathematical Model.

    Directory of Open Access Journals (Sweden)

    Ibrahim Diakite

    2016-08-01

    Full Text Available During the 2014 Ebola virus disease (EVD outbreak, policy-makers were confronted with difficult decisions on how best to test the efficacy of EVD vaccines. On one hand, many were reluctant to withhold a vaccine that might prevent a fatal disease from study participants randomized to a control arm. On the other, regulatory bodies called for rigorous placebo-controlled trials to permit direct measurement of vaccine efficacy prior to approval of the products. A stepped-wedge cluster study (SWCT was proposed as an alternative to a more traditional randomized controlled vaccine trial to address these concerns. Here, we propose novel "ordered stepped-wedge cluster trial" (OSWCT designs to further mitigate tradeoffs between ethical concerns, logistics, and statistical rigor.We constructed a spatially structured mathematical model of the EVD outbreak in Sierra Leone. We used the output of this model to simulate and compare a series of stepped-wedge cluster vaccine studies. Our model reproduced the observed order of first case occurrence within districts of Sierra Leone. Depending on the infection risk within the trial population and the trial start dates, the statistical power to detect a vaccine efficacy of 90% varied from 14% to 32% for standard SWCT, and from 67% to 91% for OSWCTs for an alpha error of 5%. The model's projection of first case occurrence was robust to changes in disease natural history parameters.Ordering clusters in a step-wedge trial based on the cluster's underlying risk of infection as predicted by a spatial model can increase the statistical power of a SWCT. In the event of another hemorrhagic fever outbreak, implementation of our proposed OSWCT designs could improve statistical power when a step-wedge study is desirable based on either ethical concerns or logistical constraints.

  3. Efficacy of pentavalent rotavirus vaccine in a high HIV prevalence population in Kenya.

    Science.gov (United States)

    Feikin, Daniel R; Laserson, Kayla F; Ojwando, Joel; Nyambane, Geoffrey; Ssempijja, Victor; Audi, Allan; Nyakundi, Daveline; Oyieko, Janet; Dallas, Michael J; Ciarlet, Max; Neuzil, Kathleen M; Breiman, Robert F

    2012-04-27

    Rotavirus gastroenteritis (RVGE) is a leading cause of death in African children. The efficacy of pentavalent rotavirus vaccine (PRV) against severe RVGE evaluated in Ghana, Kenya, and Mali in a randomized, double-blind, placebo-controlled trial, showed a combined regional efficacy of 39.3% (95% confidence interval [CI]: 19.1,54.7) in nearly 2 years of follow-up. This report concentrates on the Kenya findings. Infants received 3 doses of PRV/placebo at approximately 6-, 10-, and 14-weeks of age. HIV testing was offered to all participants. Data on illness symptoms and signs were collected upon presentation to healthcare facilities, where stools were collected, and analyzed by rotavirus-specific enzyme-linked immunosorbent assay. The primary endpoint was severe RVGE (Vesikari score ≥ 11), occurring ≥ 14 days following the third dose. At monthly home visits, symptoms of illnesses during the past 2 weeks were solicited and limited physical exams were performed; dehydration was defined by WHO's Integrated Management of Childhood Illness. Vaccine efficacy (VE) against severe RVGE through nearly 2 years of follow-up among 1308 Kenyan children was 63.9% (95% CI: -5.9,89.8). Through the first year of life, VE against severe RVGE was 83.4% (95% CI: 25.5,98.2). From home visits, VE against all-cause gastroenteritis with severe dehydration was 34.4% (95% CI: 5.3,54.6) through the first year and 29.7% (95% CI: 2.5,49.3) through the entire follow-up period. The reduction in incidence of gastroenteritis with severe dehydration in the community during the first year of life (19.0 cases/100 person-years) was almost six times greater than the reduction in severe RVGE presenting to the clinic (3.3/100 person-years). Oral rehydration solution use was lower among PRV recipients (VE 23.1%, 95% CI: 8.8,35.1). An estimated 41% of gastroenteritis with severe dehydration in the first year reported at home was rotavirus-related. PRV significantly reduced severe RVGE in Kenya. The impact

  4. Protein energy malnutrition during vaccination has limited influence on vaccine efficacy but abolishes immunity if administered during Mycobacterium tuberculosis infection.

    Science.gov (United States)

    Hoang, Truc; Agger, Else Marie; Cassidy, Joseph P; Christensen, Jan P; Andersen, Peter

    2015-05-01

    Protein energy malnutrition (PEM) increases susceptibility to infectious diseases, including tuberculosis (TB), but it is not clear how PEM influences vaccine-promoted immunity to TB. We demonstrate that PEM during low-level steady-state TB infection in a mouse model results in rapid relapse of Mycobacterium tuberculosis, as well as increased pathology, in both Mycobacterium bovis BCG-vaccinated and unvaccinated animals. PEM did not change the overall numbers of CD4 T cells in BCG-vaccinated animals but resulted in an almost complete loss of antigen-specific cytokine production. Furthermore, there was a change in cytokine expression characterized by a gradual loss of multifunctional antigen-specific CD4 T cells and an increased proportion of effector cells expressing gamma interferon and tumor necrosis factor alpha (IFN-γ(+) TNF-α(+) and IFN-γ(+) cells). PEM during M. tuberculosis infection completely blocked the protection afforded by the H56-CAF01 subunit vaccine, and this was associated with a very substantial loss of the interleukin-2-positive memory CD4 T cells promoted by this vaccine. Similarly, PEM during the vaccination phase markedly reduced the H56-CAF01 vaccine response, influencing all cytokine-producing CD4 T cell subsets, with the exception of CD4 T cells positive for TNF-α only. Importantly, this impairment was reversible and resupplementation of protein during infection rescued both the vaccine-promoted T cell response and the protective effect of the vaccine against M. tuberculosis infection. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  5. Methodology and lessons-learned from the efficacy clinical trial of the pentavalent rotavirus vaccine in Bangladesh.

    Science.gov (United States)

    Zaman, K; Yunus, M; El Arifeen, Shams; Azim, Tasnim; Faruque, A S G; Huq, Ehsanul; Hossain, Ilias; Luby, Stephen P; Victor, John C; Dallas, Michael J; Lewis, Kristen D C; Rivers, Stephen B; Steele, A Duncan; Neuzil, Kathleen M; Ciarlet, Max; Sack, David A

    2012-04-27

    An efficacy clinical trial with pentavalent rotavirus vaccine (PRV), RotaTeq(®), was conducted at Matlab field site of ICDDR,B, Bangladesh from March 2007 to March 2009. The methodology, including operation logistics, and lessons-learned are described in this report. Vaccination was organized at 41 fixed-site clinics twice/month. A total of 1136 infants were randomized 1:1 to receive 3 doses of PRV/placebo at approximately 6-, 10-, and 14-weeks of age with routine vaccines of the Expanded Programme on Immunization (EPI) schedule. Twelve field-workers routinely visited study participants for safety and efficacy follow-up. The study was conducted following good clinical practices and maintaining cold-chain requirements. There were no temperature deviations of clinical vaccine supplies. Data entry was done using the source documents to a central database developed by the sponsor which was linked to web. Among enrolled infants, 1128 (99.3%) received 3 doses of PRV/placebo and efficacy follow-up was conducted for a median of 554 days. For the evaluation of immunogenicity, blood samples were collected from 150 participants predose 1 and from 147 (98%) of the same participants post dose 3. Stool samples were collected from 778 (99.9%) acute gastroenteritis episodes among children who reported to diarrhoea treatment centres. Thirty-nine serious adverse events, including 6 deaths, occurred among study participants. The efficacy of PRV against severe rotavirus gastroenteritis was 42.7% through the entire follow-up period; serum anti-rotavirus IgA response was 78.1%. Inclement weather, difficult transportation, and movement of study participants were some of the challenges identified. This is the first vaccine trial in rural Bangladesh with online data entry. The study was well accepted in the community and was completed successfully. Copyright © 2011 Elsevier Ltd. All rights reserved.

  6. Serologic evaluation, efficacy, and safety of a commerical modified-live canine distemper vaccine in domestic ferrets.

    Science.gov (United States)

    Wimsatt, J; Jay, M T; Innes, K E; Jessen, M; Collins, J K

    2001-05-01

    To determine efficacy and safety of a commercial modified-live canine distemper virus (CDV) vaccine used for prophylaxis in domestic ferrets. Sixteen 16-week-old neutered male ferrets. Equal groups of ferrets were inoculated subcutaneously at 16 and 20 weeks of age with saline (0.9% NaCl) solution or a vaccine derived from the Onderstepoort CDV strain and attenuated in a primate cell line. Live virulent CDV was administered to all ferrets intranasally and orally 3 weeks after the second inoculation. Clinical signs and body weights were monitored regularly during the study. Blood samples for serologic examination were drawn prior to each inoculation, before challenge exposure, and 10, 15, and 21 days after exposure. Blood samples for reverse transcriptase polymerase chain reaction (RT-PCR) were obtained 5 days after the first vaccination, and 5, 10, 15, and 21 days after challenge exposure. After challenge exposure, control ferrets had significantly more clinical signs and weight loss, compared with vaccinates. All vaccinated ferrets survived, whereas all control ferrets died. The RT-PCR assay was successful in detecting CDV in blood and fresh or formalin-fixed tissues from infected ferrets. Findings suggest that the vaccine when given SC to domestic ferrets as directed is safe and protective against challenge exposure with virulent CDV. The RT-PCR assay may simplify detection of CDV in fresh and fixed tissues.

  7. Efficacy of a new bivalent vaccine of porcine circovirus type 2 and Mycoplasma hyopneumoniae (Fostera™ PCV MH) under experimental conditions.

    Science.gov (United States)

    Park, Changhoon; Jeong, Jiwoon; Choi, Kyuhyung; Chae, Chanhee

    2016-01-04

    The objective of this study was to evaluate the efficacy of a new bivalent vaccine (Fostera™ PCV MH, Zoetis) of porcine circovirus type 2 (PCV2) and Mycoplasma hyopneumoniae in growing pigs under experimental conditions. A total of 80 pigs were randomly divided into 8 groups (10 pigs per group). The pigs were administered the bivalent vaccine intramuscularly as a 2.0 mL dose at 21 days of age based on the manufacturer's instructions. Three weeks after vaccination, the pigs were inoculated with either PCV2 (intranasal route) or M. hyopneumoniae (intratracheal route) or both. Regardless of the type of inoculation, vaccinated pigs after challenge exhibited effective reduction of clinical signs, PCV2 viremia levels and mycoplasma nasal shedding, and lung and lymphoid lesion when compared to unvaccinated challenged pigs. Vaccinated challenged pigs had significantly higher (Phyopneumoniae-specific interferon-γ secreting cells compared to unvaccinated challenged pigs. This study demonstrates that the bivalent vaccine is able to protect pigs against either PCV2 or M. hyopneumoniae infection or both based on clinical, microbiological, immunological, and pathological evaluation. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Comparative Efficacy of Feline Leukemia Virus (FeLV) Inactivated Whole-Virus Vaccine and Canarypox Virus-Vectored Vaccine during Virulent FeLV Challenge and Immunosuppression.

    Science.gov (United States)

    Patel, M; Carritt, K; Lane, J; Jayappa, H; Stahl, M; Bourgeois, M

    2015-07-01

    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.

  9. [Predicting spread of new pandemic swine-origin influenza A (H1N1) in local mid-size city: evaluation of hospital bed shortage and effectiveness of vaccination].

    Science.gov (United States)

    Takeuchi, Shouhei; Kuroda, Yoshiki

    2010-01-01

    On April 24th, 2009, a new swine-origin influenza A (H1N1) was first reported in Mexico. Japan confirmed cases of the flu on May 9th, and the pandemic in Japan has become full-scale. The Ministry of Health, Labor and Welfare of Japan announced that the first peak of this pandemic was predicted to occur in October, 2009. Therefore, it is most important to predict the progress of this pandemic to be able to use medical resources effectively in Japan. We used a modified susceptible-exposed-infected-recovered (SEIR) model to calculate the number of infected people and hospital bed shortage during this pandemic. In this model, available medical resources were investigated on the basis of four vaccination scenarios. Our model showed that it would take a further six months for the pandemic to peak than was predicted by the Ministry of Health, Labor and Welfare of Japan. Without vaccination, at the peak of the pandemic 23,689 out of 400,000 people would be infected and the hospital bed shortage would reach 7,349 in total. We suggest that mathematical models are strong tools to predict the spread of infectious diseases. According to our model, it is possible to prevent hospital bed shortage by vaccination.

  10. [VACCINES].

    Science.gov (United States)

    Bellver Capella, Vincente

    2015-10-01

    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.

  11. The impact of communications about swine flu (influenza A H1N1v) on public responses to the outbreak: results from 36 national telephone surveys in the UK.

    Science.gov (United States)

    Rubin, G J; Potts, H W W; Michie, S

    2010-07-01

    respondents were very or fairly likely to accept the swine flu vaccine. The strongest predictors were being very worried about the possibility of oneself [adjusted odds ratio (aOR) 4.7, 95% confidence interval (CI) 3.2 to 7.0] or one's child (aOR 8.0, 95% CI 4.6 to 13.9) catching swine flu. Overall, 33.1% of participants reporting carrying tissues with them, 9.5% had bought sanitising gel, 2.0% had avoided public transport and 1.6% had sought medical advice. Exposure to media coverage or advertising about swine flu increased tissue carrying or buying of sanitising hand gel, and reduced avoidance of public transport or consultation with health services during early May 2009. Path analyses showed that media coverage and advertising had these differential effects because they raised the perceived efficacy of hygiene behaviours but decreased the perceived efficacy of avoidance behaviours. During the swine flu outbreak, uptake rates for protective behaviours and likely acceptance rates for vaccination were low. One reason for this may in part be explained by was the low level of public worry about the possibility of catching swine flu. When levels of worry are generally low, acting to increase the volume of mass media and advertising coverage is likely to increase the perceived efficacy of recommended behaviours, which, in turn, is likely to increase their uptake.

  12. Physical examination of swine.

    Science.gov (United States)

    Masters, B J; Hamilton, M; Masters, P G

    1992-07-01

    Swine may be examined to evaluate a disease state or a lowered economic performance or as a herd health consultation. As much of the examination as possible should be performed without handling the animal. A thorough history, evaluation of herd records, environmental examination, and herd examination should be performed prior to the evaluation of an individual animal. All necessary equipment should be available when starting the individual examination. The animals is then restrained and examined, and necessary samples are taken. Post-mortem examinations or slaughter house evaluations are a very frequent part of a health examination on swine. All samples taken should be in accordance with the standards of the laboratory that you use. You should work closely with the laboratory to obtain the best results. Physical examination of swine can be rewarding for the veterinarian as well as the producer. The most important aspect to remember is to have enough information and the proper equipment available to handle the animals for the minimal amount of time to gain the maximum benefits. Vietnamese pot-bellied pigs are similar to domestic swine in terms of their diseases and health but are dissimilar in management; pot-bellied pigs are frequently brought to the veterinarian for individual examinations. History is the most valuable part of the examination, followed by observation. Pot-bellied pigs prefer to be held securely with a hand under the chin and rump. The examination is conducted similarly to the examination of any companion animal. Chemical restraint often is necessary for sampling or minor surgical procedures. Owners should be consulted prior to the use of any restraint. This will help win their approval and confidence when working on their pets. While performing the physical examination, look at the pig's overall health as well as specific breed characteristics. Try to stay abreast of swine vaccination recommendations; you may be consulted in this regard. Most

  13. A phase 2b randomized, controlled trial of the efficacy of the GMZ2 malaria vaccine in African children

    DEFF Research Database (Denmark)

    Sirima, Sodiomon B; Mordmüller, Benjamin; Milligan, Paul

    2016-01-01

    randomized to receive three injections of either 100μg GMZ2 adjuvanted with aluminum hydroxide or a control vaccine (rabies) four weeks apart and were followed up for six months to measure the incidence of malaria defined as fever or history of fever and a parasite density ⩾5000/μL. RESULTS: A cohort of 1849...... in the rabies vaccine group and 14 in the GMZ2 group), VE 27% (95% CI -44%, 63%). CONCLUSIONS: GMZ2 is the first blood-stage malaria vaccine to be evaluated in a large multicenter trial. GMZ2 was well tolerated and immunogenic, and reduced the incidence of malaria, but efficacy would need to be substantially...

  14. Relative Efficacy of AS03-Adjuvanted Pandemic Influenza A(H1N1) Vaccine in Children: Results of a Controlled, Randomized Efficacy Trial

    Science.gov (United States)

    Nolan, Terry; Roy-Ghanta, Sumita; Montellano, May; Weckx, Lily; Ulloa-Gutierrez, Rolando; Lazcano-Ponce, Eduardo; Kerdpanich, Angkool; Safadi, Marco Aurélio Palazzi; Cruz-Valdez, Aurelio; Litao, Sandra; Lim, Fong Seng; de Los Santos, Abiel Mascareñas; Weber, Miguel Angel Rodriguez; Tinoco, Juan-Carlos; Mezerville, Marcela Hernandez-de; Faingezicht, Idis; Kosuwon, Pensri; Lopez, Pio; Borja-Tabora, Charissa; Li, Ping; Durviaux, Serge; Fries, Louis; Dubin, Gary; Breuer, Thomas; Innis, Bruce L.; Vaughn, David W.

    2014-01-01

    Background. The vaccine efficacy (VE) of 1 or 2 doses of AS03-adjuvanted influenza A(H1N1) vaccine relative to that of 2 doses of nonadjuvanted influenza A(H1N1) vaccine in children 6 months to <10 years of age in a multinational study conducted during 2010–2011. Methods. A total of 6145 children were randomly assigned at a ratio of 1:1:1 to receive 2 injections 21 days apart of A/California/7/2009(H1N1)-AS03 vaccine at dose 1 and saline placebo at dose 2, 2 doses 21 days apart of A/California/7/2009(H1N1)-AS03 vaccine (the Ad2 group), or 2 doses 21 days apart of nonadjuvanted A/California/7/2009(H1N1) vaccine (the NAd2 group). Active surveillance for influenza-like illnesses continued from days 14 to 385. Nose and throat samples obtained during influenza-like illnesses were tested for A/California/7/2009(H1N1), using reverse-transcriptase polymerase chain reaction. Immunogenicity, reactogenicity, and safety were assessed. Results. There were 23 cases of confirmed 2009 pandemic influenza A(H1N1) (A[H1N1]pdm09) infection for the primary relative VE analysis. The VE in the Ad2 group relative to that in the NAd2 group was 76.8% (95% confidence interval, 18.5%–93.4%). The benefit of the AS03 adjuvant was demonstrated in terms of the greater immunogenicity observed in the Ad2 group, compared with the NAd2 group. Conclusion. The 4–8-fold antigen-sparing adjuvanted pandemic influenza vaccine demonstrated superior and clinically important prevention of A(H1N1)pdm09 infection, compared with nonadjuvanted vaccine, with no observed increase in medically attended or serious adverse events. These data support the use of adjuvanted influenza vaccines during influenza pandemics. Clinical Trials Registration. NCT01051661. PMID:24652494

  15. Exploring of primate models of tick-borne flaviviruses infection for evaluation of vaccines and drugs efficacy.

    Directory of Open Access Journals (Sweden)

    Natalia S Pripuzova

    Full Text Available Tick-borne encephalitis virus (TBEV is one of the most prevalent and medically important tick-borne arboviruses in Eurasia. There are overlapping foci of two flaviviruses: TBEV and Omsk hemorrhagic fever virus (OHFV in Russia. Inactivated vaccines exist only against TBE. There are no antiviral drugs for treatment of both diseases. Optimal animal models are necessary to study efficacy of novel vaccines and treatment preparations against TBE and relative flaviviruses. The models for TBE and OHF using subcutaneous inoculation were tested in Cercopithecus aethiops and Macaca fascicularis monkeys with or without prior immunization with inactivated TBE vaccine. No visible clinical signs or severe pathomorphological lesions were observed in any monkey infected with TBEV or OHFV. C. aethiops challenged with OHFV showed massive hemolytic syndrome and thrombocytopenia. Infectious virus or viral RNA was revealed in visceral organs and CNS of C. aethiops infected with both viruses; however, viremia was low. Inactivated TBE vaccines induced high antibody titers against both viruses and expressed booster after challenge. The protective efficacy against TBE was shown by the absence of virus in spleen, lymph nodes and CNS of immunized animals after challenge. Despite the absence of expressed hemolytic syndrome in immunized C. aethiops TBE vaccine did not prevent the reproduction of OHFV in CNS and visceral organs. Subcutaneous inoculation of M. fascicularis with two TBEV strains led to a febrile disease with well expressed viremia, fever, and virus reproduction in spleen, lymph nodes and CNS. The optimal terms for estimation of the viral titers in CNS were defined as 8-16 days post infection. We characterized two animal models similar to humans in their susceptibility to tick-borne flaviviruses and found the most optimal scheme for evaluation of efficacy of preventive and therapeutic preparations. We also identified M. fascicularis to be more susceptible to

  16. Design and statistical considerations for studies evaluating the efficacy of a single dose of the human papillomavirus (HPV) vaccine.

    Science.gov (United States)

    Sampson, Joshua N; Hildesheim, Allan; Herrero, Rolando; Gonzalez, Paula; Kreimer, Aimee R; Gail, Mitchell H

    2018-05-01

    Cervical cancer is a leading cause of cancer mortality in women worldwide. Human papillomavirus (HPV) types 16 and 18 cause about 70% of all cervical cancers. Clinical trials have demonstrated that three doses of either commercially available HPV vaccine, Cervarix ® or Gardasil ®, prevent most new HPV 16/18 infections and associated precancerous lesions. Based on evidence of immunological non-inferiority, 2-dose regimens have been licensed for adolescents in the United States, European Union, and elsewhere. However, if a single dose were effective, vaccine costs would be reduced substantially and the logistics of vaccination would be greatly simplified, enabling vaccination programs in developing countries. The National Cancer Institute (NCI) and the Agencia Costarricense de Investigaciones Biomédicas (ACIB) are conducting, with support from the Bill & Melinda Gates Foundation and the International Agency for Research on Cancer (IARC), a large 24,000 girl study to evaluate the efficacy of a 1-dose regimen. The first component of the study is a four-year non-inferiority trial comparing 1- to 2-dose regimens of the two licensed vaccines. The second component is an observational study that estimates the vaccine efficacy (VE) of each regimen by comparing the HPV infection rates in the trial arms to those in a contemporaneous survey group of unvaccinated girls. In this paper, we describe the design and statistical analysis for this study. We explain the advantage of defining non-inferiority on the absolute risk scale when the expected event rate is near 0 and, given this definition, suggest an approach to account for missing clinic visits. We then describe the problem of estimating VE in the absence of a randomized placebo arm and offer our solution. Copyright © 2018. Published by Elsevier Inc.

  17. 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.

    Science.gov (United States)

    Hemann, Michelle; Beach, Nathan M; Meng, Xiang-Jin; Wang, Chong; Halbur, Patrick G; Opriessnig, Tanja

    2014-01-01

    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.

  18. Rotavirus vaccines

    Directory of Open Access Journals (Sweden)

    Kang G

    2006-01-01

    Full Text Available Rotavirus, the most common cause of severe diarrhea and a leading cause of mortality in children, has been a priority target for vaccine development for the past several years. The first rotavirus vaccine licensed in the United States was withdrawn because of an association of the vaccine with intussusception. However, the need for a vaccine is greatest in the developing world, because the benefits of preventing deaths due to rotavirus disease are substantially greater than the risk of intussusception. Early vaccines were based on animal strains. More recently developed and licenced vaccines are either animal-human reassortants or are based on human strains. In India, two candidate vaccines are in the development process, but have not yet reached efficacy trials. Many challenges regarding vaccine efficacy and safety remain. In addition to completing clinical evaluations of vaccines in development in settings with the highest disease burden and virus diversity, there is also a need to consider alternative vaccine development strategies.

  19. A pooled analysis of continued prophylactic efficacy of quadrivalent human papillomavirus (Types 6/11/16/18) vaccine against high-grade cervical and external genital lesions

    DEFF Research Database (Denmark)

    Kjaer, Susanne K; Sigurdsson, Kristján; Iversen, Ole-Erik

    2009-01-01

    Quadrivalent human papillomavirus (HPV) vaccine has been shown to provide protection from HPV 6/11/16/18-related cervical, vaginal, and vulvar disease through 3 years. We provide an update on the efficacy of the quadrivalent HPV vaccine against high-grade cervical, vaginal, and vulvar lesions bas...

  20. The EG95 Antigen of Echinococcus spp. Contains Positively Selected Amino Acids, which May Influence Host Specificity and Vaccine Efficacy

    Science.gov (United States)

    Haag, Karen Luisa; Gottstein, Bruno; Ayala, Francisco Jose

    2009-01-01

    Echinococcosis is a worldwide zoonotic parasitic disease of humans and various herbivorous domestic animals (intermediate hosts) transmitted by the contact with wild and domestic carnivores (definitive hosts), mainly foxes and dogs. Recently, a vaccine was developed showing high levels of protection against one parasite haplotype (G1) of Echinococcus granulosus, and its potential efficacy against distinct parasite variants or species is still unclear. Interestingly, the EG95 vaccine antigen is a secreted glycosylphosphatydilinositol (GPI)-anchored protein containing a fibronectin type III domain, which is ubiquitous in modular proteins involved in cell adhesion. EG95 is highly expressed in oncospheres, the parasite life cycle stage which actively invades the intermediate hosts. After amplifying and sequencing the complete CDS of 57 Echinococcus isolates belonging to 7 distinct species, we uncovered a large amount of genetic variability, which may influence protein folding. Two positively selected sites are outside the vaccine epitopes, but are predicted to alter protein conformation. Moreover, phylogenetic analyses indicate that EG95 isoform evolution is convergent with regard to the number of beta-sheets and alpha-helices. We conclude that having a variety of EG95 isoforms is adaptive for Echinococcus parasites, in terms of their ability to invade different hosts, and we propose that a mixture of isoforms could possibly maximize vaccine efficacy. PMID:19401778

  1. Safety and efficacy of an attenuated Chinese QX-like infectious bronchitis virus strain as a candidate vaccine.

    Science.gov (United States)

    Zhao, Ye; Cheng, Jin-long; Liu, Xiao-yu; Zhao, Jing; Hu, Yan-xin; Zhang, Guo-zhong

    2015-10-22

    Infectious bronchitis (IB) is a highly contagious respiratory and urogenital disease of chickens caused by infectious bronchitis virus (IBV). This disease is of considerable economic importance and is primarily controlled through biosecurity and immunization with live attenuated and inactivated IB vaccines of various serotypes. In the present study, we tested the safety and efficacy of an attenuated predominant Chinese QX-like IBV strain. The results revealed that the attenuated strain has a clear decrease in pathogenicity for specific-pathogen-free (SPF) chickens compared with the parent strain. Strain YN-inoculated birds had clinical signs of varying severity with 30% mortality, while the attenuated group appeared healthy, with less tissue damage. The attenuated strain also had relatively low tissue replication rates and higher antibody levels. The superior protective efficacy of the attenuated strain was observed when vaccinated birds were challenged with a homologous or heterologous field IBV strain, indicating the potential of the attenuated YN (aYN) as a vaccine. Producing a vaccine targeting the abundant serotype in China is essential to reducing the economic impact of IB on the poultry industry. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Efficacy and safety of human papillomavirus vaccine for primary prevention of cervical cancer: A review of evidence from phase III trials and national programs

    Directory of Open Access Journals (Sweden)

    Partha Basu

    2013-01-01

    Full Text Available The Human Papillomavirus (HPV vaccines have been widely introduced in the national immunization programs in most of the medium and high income countries following endorsement from national and international advisory bodies. HPV vaccine is unique and its introduction is challenging in many ways - it is the first vaccine developed to prevent any cancer, the vaccine is gender specific, it targets adolescent females who are difficult to reach by any health intervention programs. It is not unusual for such a vaccine to face scepticism and reservations not only from lay public but also from professionals in spite of the clinical trial results convincingly and consistently proving their efficacy and safety. Over the last few years millions of doses of the HPV vaccine have been administered round the world and the efficacy and safety data have started coming from the real life programs. A comprehensive cervical cancer control program involving HPV vaccination of the adolescent girls and screening of the adult women has been proved to be the most cost-effective approach to reduce the burden of cervical cancer. The present article discusses the justification of HPV vaccination in the backdrop of natural history of cervical cancer, the mechanism of action of the vaccines, efficacy and safety data from phase III randomized controlled trials as well as from the national immunization programs of various countries.

  3. 9 CFR 85.7 - Interstate movement of swine not vaccinated for pseudorabies and not known to be infected with or...

    Science.gov (United States)

    2010-01-01

    ... § 85.1, states the identification of the farm of origin of each swine being moved by a means of... pseudorabies shall only be moved interstate in accordance with the following provisions: (a) Movement for... pseudorabies may be moved interstate for slaughter without further restriction under this part directly to a...

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

    Science.gov (United States)

    Wood, David

    2005-12-01

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

  5. Efficacy of hepatitis B vaccine against antiviral drug-resistant hepatitis B virus mutants in the chimpanzee model.

    Science.gov (United States)

    Kamili, Saleem; Sozzi, Vitini; Thompson, Geoff; Campbell, Katie; Walker, Christopher M; Locarnini, Stephen; Krawczynski, Krzysztof

    2009-05-01

    Hepatitis B virus (HBV) mutants resistant to treatment with nucleoside or nucleotide analogs and those with the ability to escape from HBV-neutralizing antibody have the potential to infect HBV-vaccinated individuals. To address this potential serious public health challenge, we tested the efficacy of immunity induced by a commercial hepatitis B vaccine against a tissue culture-derived, clonal HBV polymerase mutant in HBV seronegative chimpanzees. The polymerase gene mutant contained a combination of three mutations (rtV173L, rtL180M, rtM204V), two of which resulted in changes to the overlapping viral envelope of the hepatitis B surface antigen (sE164D, sI195M). Prior to the HBV mutant challenge of vaccinated chimpanzees, we established virologic, serologic, and pathologic characteristics of infections resulting from intravenous inoculation of the HBV polymerase gene mutant and the sG145R vaccine-escape surface gene mutant. Cloning and sequencing experiments determined that the three mutations in the polymerase gene mutant remained stable and that the single mutation in the surface gene mutant reverted to the wild-type sequence. Immunological evidence of HBV replication was observed in the vaccinated chimpanzees after challenge with the polymerase gene mutant as well as after rechallenge with serum-derived wild-type HBV (5,000 chimpanzee infectious doses administered intravenously), despite robust humoral and cellular anti-HBV immune responses after hepatitis B vaccination. Our data showing successful experimental infection by HBV mutants despite the presence of high anti-HBs levels considered protective in the vaccinated host are consistent with clinical reports on breakthrough infection in anti-HBs-positive patients infected with HBV mutants. In the absence of a protective humoral immunity, adaptive cellular immune responses elicited by infection may limit HBV replication and persistence.

  6. Efficacy of a pentavalent human-bovine reassortant rotavirus vaccine against rotavirus gastroenteritis among American Indian children.

    Science.gov (United States)

    Grant, Lindsay R; Watt, James P; Weatherholtz, Robert C; Moulton, Lawrence H; Reid, Raymond; Santosham, Mathuram; O'Brien, Katherine L

    2012-02-01

    Before the widespread use of rotavirus vaccines, rotavirus was a leading cause of gastroenteritis among children. Navajo and White Mountain Apache children suffer a disproportionate burden of severe rotavirus disease compared with the general U.S. population. We enrolled Navajo and White Mountain Apache infants in a multicenter, double-blind, placebo-controlled trial of pentavalent human-bovine reassortant rotavirus vaccine (PRV). Subjects received 3 doses of vaccine or placebo at 4 to 10 week intervals, with the first dose given between 6 and 12 weeks of age. Gastroenteritis episodes were identified by active surveillance. Disease severity was determined by a standardized scoring system. There were 509 and 494 randomized children who received vaccine and placebo, respectively. Among placebo recipients, the incidence of rotavirus gastroenteritis was 34.2 episodes/100 child-years (95% confidence interval [95% CI]: 25.8-38.9) versus 8.1 episodes/100 child-years (95% CI: 5.4-12.5) in the vaccine group. The percentage of rotavirus episodes caused by serotypes G1, G2, and G3 was 72.3%, 23.4%, and 2.1%, respectively. There were no severe rotavirus episodes among vaccinees and 4 among placebo recipients. PRV was 77.1% (95% CI: 59.7-87.6), 89.5% (95% CI: 65.9-97.9), and 82.9% (95% CI: 61.1-93.6) effective against G1-G4 rotavirus disease, severe and moderate rotavirus disease combined, and outpatient visits for rotavirus disease, respectively. The risk of adverse events was similar for the vaccine and placebo groups. PRV was highly effective in preventing rotavirus disease and related health care utilization in these American Indian infants. Vaccine efficacy and immunogenicity were similar to the overall study population enrolled in the multicenter trial.

  7. Efficacy of recombinant birch pollen vaccine for the treatment of birch-allergic rhinoconjunctivitis

    DEFF Research Database (Denmark)

    Pauli, Gabrielle; Larsen, Tina H; Rak, Sabina

    2008-01-01

    BACKGROUND: Recombinant DNA technology has the potential to produce allergen-specific immunotherapy vaccines with defined composition. OBJECTIVE: To evaluate the effectiveness of a new recombinant birch pollen allergen vaccine in patients with birch pollen allergy. METHODS: A multicenter, randomi......-treated group. CONCLUSION: The rBet v 1-based vaccine was safe and effective in treating birch pollen allergy, and induced a highly specific immune response.......BACKGROUND: Recombinant DNA technology has the potential to produce allergen-specific immunotherapy vaccines with defined composition. OBJECTIVE: To evaluate the effectiveness of a new recombinant birch pollen allergen vaccine in patients with birch pollen allergy. METHODS: A multicenter......, randomized, double-blind, placebo-controlled trial was undertaken to compare the following 3 vaccines in 134 adults with birch pollen allergy: recombinant birch pollen allergen vaccine (rBet v 1a), licensed birch pollen extract, natural purified birch pollen allergen (nBet v 1), and placebo. Patients...

  8. Protein energy malnutrition during vaccination has limited influence on vaccine efficacy but abolishes immunity if administered during Mycobacterium tuberculosis infection

    DEFF Research Database (Denmark)

    Hoang, Truc; Agger, Else Marie; Cassidy, Joseph P

    2015-01-01

    Protein energy malnutrition (PEM) increases susceptibility to infectious diseases, including tuberculosis (TB), but it is not clear how PEM influences vaccine-promoted immunity to TB. We demonstrate that PEM during low-level steady-state TB infection in a mouse model results in rapid relapse...

  9. H1N1 influenza (Swine flu)

    Science.gov (United States)

    Swine flu; H1N1 type A influenza ... The H1N1 virus is now considered a regular flu virus. It is one of the three viruses included in the regular (seasonal) flu vaccine . You cannot get H1N1 flu virus from ...

  10. ISCOM-based equine influenza vaccine: Duration of immunity and randomised clinical trials to assess an accelerated schedule of immunisation and efficacy

    Directory of Open Access Journals (Sweden)

    R. Paillot

    2015-01-01

    Study 3: efficacy against Florida clade 2 EIV strain (randomised trial. Efficacy against the representative Florida clade 2 strain A/eq/Richmond/1/07 was also evaluated at the peak of immunity, shortly after 2nd vaccination (V2. Six ponies were vaccinated with EquipFT according to label (6-week interval between first and second injection and 6 control ponies received saline injections. Sixteen days after V2 (day 58, all animals were experimentally infected with A/eq/Richmond/1/07. Clinical signs of disease and virus shedding were assessed for 14 days and found to be significantly reduced in vaccinated animals.

  11. CRISPR-Cas9, a tool to efficiently increase the development of recombinant African swine fever viruses

    Science.gov (United States)

    African swine fever is a contagious and often lethal disease for domestic pigs with a significant economic impact on the swine industry. The etiological agent, African swine fever virus (ASFV), is a highly structurally complex double stranded DNA virus. No effective vaccines or antiviral treatment ...

  12. 2-Year Efficacy, Immunogenicity, and Safety of Vigoo Enterovirus 71 Vaccine in Healthy Chinese Children: A Randomized Open-Label Study.

    Science.gov (United States)

    Wei, Mingwei; Meng, Fanyue; Wang, Shiyuan; Li, Jingxin; Zhang, Yuntao; Mao, Qunying; Hu, Yuemei; Liu, Pei; Shi, Nianmin; Tao, Hong; Chu, Kai; Wang, Yuxiao; Liang, Zhenglun; Li, Xiuling; Zhu, Fengcai

    2017-01-01

     This study evaluated the 2-year efficacy, immunogenicity, and safety of the Vigoo enterovirus 71 (EV71) vaccine.  In an initial phase 3 study, we randomly assigned healthy infants and children aged 6-35 months (ratio, 1:1) to receive 2 doses of either EV71 vaccine (5120 participants) or placebo (5125 participants) at days 0 and 28, and followed them for 12 months after vaccination. In this extended follow-up study, we continued to evaluate the efficacy, immunogenicity, and safety of the EV71 vaccine for up to 2 years.  Overall efficacy was 94.84% (95% confidence interval [CI], 83.53%-98.38%) during the 2-year follow-up period (P vaccine efficacy during the second year was 100.00% (95% CI, 84.15%-100.00%) against EV71-associated hand-foot-and-mouth disease (HFMD; P vaccine-related serious adverse events were recorded.  Two doses of Vigoo EV71 vaccine could provide sustained protection against EV71-associated HFMD in healthy Chinese children.  NCT01508247. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  13. Chimeric Pestivirus Experimental Vaccines.

    Science.gov (United States)

    Reimann, Ilona; Blome, Sandra; Beer, Martin

    2016-01-01

    Chimeric pestiviruses have shown great potential as marker vaccine candidates against pestiviral infections. Exemplarily, we describe here the construction and testing of the most promising classical swine fever vaccine candidate "CP7_E2alf" in detail. The description is focused on classical cloning technologies in combination with reverse genetics.

  14. Efficacy of DNA vaccine encoding koi herpesvirus glycoprotein GP-25in common carp juvenile by immersion

    Directory of Open Access Journals (Sweden)

    Soko Nuswantoro

    2013-11-01

    Full Text Available Koi herpesvirus (KHV is a herpesvirus that particularly infects and causes mass mortality to koi and common carp. Therefore, the protection of common carp from KHV infection is urgently needed. In this study, we developed an application of DNA vaccine encoding KHV glycoprotein-25 by immersion method to increase survival of common carp against KHV infection. A total of 400 common carp juveniles at 30-day-old were immersed in 1-L water containing 1.3×108CFU/mL of the killed Escherichia coli cells carrying DNA vaccine. Three frequencies and three duration of fish immersion were tested, namely: 1×30 minutes, 1×60 minutes, 1× 90 minutes, 2×90 minutes and 3×90 minutes by interval of 24 hours. Reversetranscription polymerase chain reaction analysis showed that DNA vaccine was successfully expressed in the vaccinated fish. Fish at twenty eight days post vaccination were challenged by injecting 10-4 mL of KHV per fish. The result showed that vaccination by 1×30 minutes immersion allowed 61% of fish survived, and this was significantly higher (p<0.05 compared to control (without vaccination, but it was similar among vaccination treatments (p>0.05. The relative percent survival of vaccinated fish were also similar among treatments (p>0.05. DNA vaccination has increased fish survival about two fold higher compared to unvaccinated fish control (26.67%. Thus, DNA vaccination was effectively delivered by immersion for 1×30 minutes, and this technique can be useful to level up the resistance of common carp juveniles against KHV infection. Keywords: DNA vaccine, KHV, glycoprotein, immersion, common carp

  15. Immunogenicity and efficacy of a chimpanzee adenovirus-vectored Rift Valley fever vaccine in mice.

    OpenAIRE

    Warimwe, GM; Lorenzo, G; Lopez-Gil, E; Reyes-Sandoval, A; Cottingham, MG; Spencer, AJ; Collins, KA; Dicks, MD; Milicic, A; Lall, A; Furze, J; Turner, AV; Hill, AV; Brun, A; Gilbert, SC

    2013-01-01

    BACKGROUND: Rift Valley Fever (RVF) is a viral zoonosis that historically affects livestock production and human health in sub-Saharan Africa, though epizootics have also occurred in the Arabian Peninsula. Whilst an effective live-attenuated vaccine is available for livestock, there is currently no licensed human RVF vaccine. Replication-deficient chimpanzee adenovirus (ChAd) vectors are an ideal platform for development of a human RVF vaccine, given the low prevalence of neutralizing antibod...

  16. Influence of virus strain and antigen mass on efficacy of H5 avian influenza inactivated vaccines.

    Science.gov (United States)

    Swayne, D E; Beck, J R; Garcia, M; Stone, H D

    1999-06-01

    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.

  17. MODERN EPIDEMIOLOGICAL PECULIARITIES OF HEPATITIS A AND EFFICACY OF UNIVERSAL VACCINATION IN CHILDREN

    Directory of Open Access Journals (Sweden)

    I.V. Shakhgil’dyan

    2010-01-01

    Full Text Available Authors described modern epidemiological peculiarities of hepatitis A in Russia. They prove reasonability of mass vaccination implementation against this infection. Results of a vaccination in children after its inclusion in Regional Calendars of Prophylactic Immunization are analyzed.Key words: children, hepatitis A, vaccinal prophylaxis, posvaccinal immunity.                 (Voprosy sovremennoi pediatrii — Current Pediatrics. – 2010;9(3:131-135

  18. 5 year efficacy of a bivalent killed whole-cell oral cholera vaccine in Kolkata, India: a cluster-randomised, double-blind, placebo-controlled trial.

    Science.gov (United States)

    Bhattacharya, Sujit K; Sur, Dipika; Ali, Mohammad; Kanungo, Suman; You, Young Ae; Manna, Byomkesh; Sah, Binod; Niyogi, Swapan K; Park, Jin Kyung; Sarkar, Banwarilal; Puri, Mahesh K; Kim, Deok Ryun; Deen, Jacqueline L; Holmgren, Jan; Carbis, Rodney; Dhingra, Mandeep Singh; Donner, Allan; Nair, G Balakrish; Lopez, Anna Lena; Wierzba, Thomas F; Clemens, John D

    2013-12-01

    Efficacy and safety of a two-dose regimen of bivalent killed whole-cell oral cholera vaccine (Shantha Biotechnics, Hyderabad, India) to 3 years is established, but long-term efficacy is not. We aimed to assess protective efficacy up to 5 years in a slum area of Kolkata, India. In our double-blind, cluster-randomised, placebo-controlled trial, we assessed incidence of cholera in non-pregnant individuals older than 1 year residing in 3933 dwellings (clusters) in Kolkata, India. We randomly allocated participants, by dwelling, to receive two oral doses of modified killed bivalent whole-cell cholera vaccine or heat-killed Escherichia coli K12 placebo, 14 days apart. Randomisation was done by use of a computer-generated sequence in blocks of four. The primary endpoint was prevention of episodes of culture-confirmed Vibrio cholerae O1 diarrhoea severe enough for patients to seek treatment in a health-care facility. We identified culture-confirmed cholera cases among participants seeking treatment for diarrhoea at a study clinic or government hospital between 14 days and 1825 days after receipt of the second dose. We assessed vaccine protection in a per-protocol population of participants who had completely ingested two doses of assigned study treatment. 69 of 31 932 recipients of vaccine and 219 of 34 968 recipients of placebo developed cholera during 5 year follow-up (incidence 2·2 per 1000 in the vaccine group and 6·3 per 1000 in the placebo group). Cumulative protective efficacy of the vaccine at 5 years was 65% (95% CI 52-74; pcholera vaccines. Established long-term efficacy of this vaccine could assist policy makers formulate rational vaccination strategies to reduce overall cholera burden in endemic settings. Bill & Melinda Gates Foundation and the governments of South Korea and Sweden. Copyright © 2013 Elsevier Ltd. All rights reserved.

  19. Efficacy of avian influenza oil-emulsion vaccines in chickens of various ages.

    Science.gov (United States)

    Stone, H D

    1987-01-01

    An experimental avian influenza (AI) oil-emulsion vaccine was formulated with 1 part inactivated A/turkey/Wisconsin/68 (H5N9) AI virus emulsified in 4 parts oil. Broilers were vaccinated subcutaneously (SC) either at 1 or 3 days old or at 4 or 5 wks old. Commercial white leghorn (WL) layers were vaccinated SC at 12 and 20 wks old or at only 20 wks old. Maximum geometric mean hemagglutination-inhibition titers postvaccination (PV) were 1:86-1:320 for broilers, 1:597 for twice-vaccinated layers, and 1:422 for once-vaccinated layers. Ninety to 100% of vaccinated broilers were protected against death and morbidity when challenged with highly pathogenic A/chicken/Penn/83 (H5N2) AI virus 4 weeks PV, and all were protected when challenged 8 wks PV. All controls and most vaccinates were infected by challenge virus, and 90-100% of controls died or exhibited clinical signs. Vaccinated commercial pullets were protected against morbidity, death, and egg-production decline at either peak of lay (25 wks old) or at 55 wks old. All unvaccinated controls became morbid or died, and egg production ceased 72 hours after challenge. The 0.5-ml vaccine dose was determined to contain 251 and 528 mean protective doses (PD50S) in 4-wk-old and 1-year-old SPF WL chickens, respectively, challenged 4 wks PV.

  20. Efficacy of a Gal-lectin subunit vaccine against experimental Entamoeba histolytica infection and colitis in baboons (Papio sp.).

    Science.gov (United States)

    Abd Alla, Mohamed D; Wolf, Roman; White, Gary L; Kosanke, Stanley D; Cary, David; Verweij, Jaco J; Zhang, Mie-Jie; Ravdin, Jonathan I

    2012-04-26

    To determine the efficacy of a Gal-lectin based intranasal synthetic peptide vaccine, we developed a new experimental primate model of Entamoeba histolytica intestinal infection. Release of xenic E. histolytica trophozoites (5×10(6)) into the small bowel of baboons (Papio sp.) resulted in a rapid intestinal anti-amebic antibody response and a brief infection; however, release of trophozoites directly into the cecum (5 baboons) elicited a sustained E. histolytica infection, as determined by quantitative fecal PCR, and an ulcerative, inflammatory colitis observed on colonoscopy and histopathology. In three controlled experiments, baboons received four immunizations at seven day intervals of 1600 μg of the vaccine/nostril, with Cholera toxin, 20 μg/nostril as adjuvant; vaccinated (n=6) and control baboons (n=6) baboons were then challenged via colonoscopy with xenic trophozoites (5×10(6)). During 90 days of follow up, 250 of 415 (60.24%) fecal samples in control baboons had a (+) PCR for E. histolytica, compared to only 36 of 423 (8.51%) samples from vaccinated baboons (P<0.001). All 6 vaccinated baboons were free of infection by the 51st day after challenge, 5 of 6 controls positive had (+) fecal PCRs for up to 126 days post-challenge (P=0.019). Inflammatory colitis developed in 4 of 6 control baboons post-challenge, with invasive E. histolytica trophozoites present in 2 of the 4 on histopathology. There was no evidence of inflammatory colitis or parasite invasion in any of the vaccinated baboons; there was a strong inverse correlation between positive ELISA OD value indicating the presence of intestinal anti-peptide IgA antibodies and baboons having a positive fecal PCR CT value, P<0.001. In conclusion, we developed a novel primate model of E. histolytica intestinal infection and demonstrated that a Gal-lectin-based intranasal synthetic peptide vaccine was highly efficacious in preventing experimental E. histolytica infection and colitis in baboons. Copyright

  1. Immunogenicity and efficacy in mice of an adenovirus-based bicistronic rotavirus vaccine expressing NSP4 and VP7.

    Science.gov (United States)

    Xie, Li; Yan, Min; Wang, Xiaonan; Ye, Jing; Mi, Kai; Yan, Shanshan; Niu, Xianglian; Li, Hongjun; Sun, Maosheng

    2015-12-02

    NSP4 and VP7 are important functional proteins of rotavirus. Proper combination of viral gene expression is favorable to improving the protection effect of subunit vaccine. In the present study, We evaluated the immunogenicity and efficacy of the bicistronic recombinant adenovirus (rAd-NSP4-VP7) and two single-gene expressing adenoviruses (rAd-NSP4, rAd-VP7). The three adenovirus vaccines were used to immunize mice by intramuscular or intranasal administration. The data showed significant increases in serum antibodies, T lymphocyte subpopulations proliferation, and cytokine secretions of splenocyte in all immunized groups. However, the serum IgA and neutralizing antibody levels of the rAd-NSP4-VP7 or rAd-VP7 groups were significantly higher than those of the rAd-NSP4, while the splenocyte numbers of IFN-γ secretion in the rAd-NSP4-VP7 or rAd-NSP4 groups was greater than that of the rAd-VP7. Furthermore, the efficacy evaluation in a suckling mice model indicated that only rAd-NSP4-VP7 conferred significant protection against rotavirus shedding challenge. These results suggest that the co-expression of NSP4 and VP7 in an adenovirus vector induce both humoral and cell-mediated immune responses efficiently, and provide potential efficacy for protection against rotavirus disease. It is possible to represent an efficacious subunits vaccine strategy for control of rotavirus infection and transmission. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Swine production.

    Science.gov (United States)

    Plain, Ronald L; Lawrence, John D

    2003-07-01

    The US swine industry is large and growing. The quantity of pork desired by consumers of US pork is growing at the rate of 1.5%/y. New production systems and new technology have enabled production per sow to grow at a rate of 4% annually in recent years. Consequently, the number of sows in the United States is declining. Because productivity growth is outpacing demand growth, the deflated price of hogs and pork is declining. Hog production and prices continue to exhibit strong seasonal and cyclic patterns. Pork production is usually lowest in the summer and highest in the fall. Production and prices tend to follow 4-year patterns. The US swine industry continues to evolve toward fewer and larger producers who rely on contracts for both hog production and marketing. In 2000, over half of the hogs marketed were from approximately 156 firms marketing more than 50,000 head annually. These producers finished 60% of their production in contract facilities. Over 90% of their marketings were under contract or were owned by a packer. These producers expressed a high level of satisfaction with hog production. Both they and their contract growers were satisfied with production contracts. These large producers were satisfied with their marketing contracts and planned to continue them in the future. The hog industry has changed a great deal in the last decade. There is little reason to believe this rapid rate of change will not continue. This swine industry is highly competitive and profit driven. Profit margins are too small to allow producers the luxury of ignoring new technology and innovative production systems. Consequently, hog production will continue its rapid evolution from traditional agriculture to typical industry.

  3. Immunoprotective efficacy of Acinetobacter baumannii outer membrane protein, FilF, predicted in silico as a potential vaccine candidate

    Directory of Open Access Journals (Sweden)

    Ravinder eSingh

    2016-02-01

    Full Text Available Acinetobacter baumannii is emerging as a serious nosocomial pathogen with multidrug resistance that has made it difficult to cure and development of efficacious treatment against this pathogen is direly needed. This has led to investigate vaccine approach to prevent and treat A. baumannii infections. In this work, an outer membrane putative pilus assembly protein, FilF, was predicted as vaccine candidate by in silico analysis of A. baumannii proteome and was found to be conserved among the A. baumannii strains. It was cloned and expressed in E. coli BL21(DE3 and purified by Ni-NTA chromatography. Immunization with FilF generated high antibody titer (>64000 and provided 50% protection against a standardized lethal dose (10*8 CFU of A. baumannii in murine pneumonia model. FilF immunization reduced the bacterial load in lungs by 2 and 4 log cycles, 12 and 24 h post infection as compared to adjuvant control; reduced the levels of pro-inflammatory cytokines TNF-α, IL-6, IL-33, IFN-γ and IL-1β significantly and histology of lung tissue supported the data by showing considerably reduced damage and infiltration of neutrophils in lungs. These results demonstrate the in vivo validation of immunoprotective efficacy of a protein predicted as a vaccine candidate by in silico proteomic analysis and open the possibilities for exploration of a large array of uncharacterized proteins.

  4. Systemic Administration of Interleukin 2 Enhances the Therapeutic Efficacy of Dendritic Cell-Based Tumor Vaccines

    Science.gov (United States)

    Shimizu, K.; Fields, R. C.; Giedlin, M.; Mule, J. J.

    1999-03-01

    We have reported previously that murine bone marrow-derived dendritic cells (DC) pulsed with whole tumor lysates can mediate potent antitumor immune responses both in vitro and in vivo. Because successful therapy was dependent on host immune T cells, we have now evaluated whether the systemic administration of the T cell stimulatory/growth promoting cytokine interleukin-2 (IL-2) could enhance tumor lysate-pulsed DC-based immunizations to further promote protective immunity toward, and therapeutic rejection of, syngeneic murine tumors. In three separate approaches using a weakly immunogenic sarcoma (MCA-207), the systemic administration of non-toxic doses of recombinant IL-2 (20,000 and 40,000 IU/dose) was capable of mediating significant increases in the potency of DC-based immunizations. IL-2 could augment the efficacy of tumor lysate-pulsed DC to induce protective immunity to lethal tumor challenge as well as enhance splenic cytotoxic T lymphocyte activity and interferon-γ production in these treated mice. Moreover, treatment with the combination of tumor lysate-pulsed DC and IL-2 could also mediate regressions of established pulmonary 3-day micrometastases and 7-day macrometastases as well as established 14- and 28-day s.c. tumors, leading to either significant cure rates or prolongation in overall survival. Collectively, these findings show that nontoxic doses of recombinant IL-2 can potentiate the antitumor effects of tumor lysate-pulsed DC in vivo and provide preclinical rationale for the use of IL-2 in DC-based vaccine strategies in patients with advanced cancer.

  5. Efficacy of an inactivated aqueous vaccine for the control of enzootic pneumonia in pigs infected with Mycoplasma hyopneumoniae.

    Science.gov (United States)

    Tzivara, A; Kritas, S K; Bourriel, A R; Alexopoulos, C; Kyriakis, S C

    2007-02-17

    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.

  6. Study on the efficacy and safety of different antigens and oil formulations of infectious coryza vaccines containing an NAD-independent strain of Avibacterium paragallinarum

    Directory of Open Access Journals (Sweden)

    B. Dungu

    2009-09-01

    Full Text Available The present study was designed to assess and compare three different formulations of the new Onderstepoort infectious coryza (IC quadrivalent vaccine, which contain an NAD-independent strain of Avibacterium paragallinarum (previously known as Haemophilus paragallinarum, and a commercial IC vaccine, not containing an NAD-independent strain, for their safety and ability to protect chickens of varying ages against virulent challenges with four different serovars of A. paragallinarum, including the NAD-independent strain of the C-3 serovar. Four groups of 140 chickens each were vaccinated at the age of 17 weeks and revaccinated at the age of 19 weeks with each of the four vaccine formulations. A similar sized group of non-vaccinated chickens was used as control. Two rounds of challenge were conducted: a group of chicken in each vaccination group was challenged between 31 and 35 weeks of age, while another group was challenged between 51 and 55 weeks of age. The ''in-contact'' challenge model was used in this experiment. For each vaccination group, the four challenge strains representing four local serovars were used in each challenge round. The efficacy of the vaccines was compared based on overall protection levels obtained and the duration of protection. The safety of the different vaccines was determined by the severity of post-vaccination reactions. The need for the incorporation of the NAD-independent strain in the vaccine was evidenced by the low protection level against NAD-independent challenge recorded in the group of birds vaccinated with the commercial vaccine. The results obtained confirmed not only the variation in virulence of different South African serovars, with serovar C-3 being the most virulent and serovar B having almost no virulence but also the age related increase in susceptibility. The importance of a suitable formulation of the vaccine is discussed.

  7. Flublok Seasonal Influenza (Flu) Vaccination

    Science.gov (United States)

    ... type="submit" value="Submit" /> Archived Flu Emails Influenza Types Seasonal Avian Swine Variant Pandemic Other Flublok Seasonal Influenza (Flu) Vaccine Questions & Answers Language: English (US) Español ...

  8. Safety and efficacy of meningococcal c vaccination in juvenile idiopathic arthritis

    NARCIS (Netherlands)

    Zonneveld-Huijssoon, Evelien; Ronaghy, Arash; van Rossum, Marion A. J.; Rijkers, Ger T.; van der Klis, Fiona R. M.; Sanders, Elisabeth A. M.; Vermeer-de Bondt, Patricia E.; Hoes, Arno W.; van der Net, Jan Jaap; Engels, Carla; Kuis, Wietse; Prakken, Berent J.; van Tol, Maarten J. D.; Wulffraat, Nico M.

    2007-01-01

    To determine whether vaccinations aggravate the course of autoimmune diseases such as juvenile idiopathic arthritis (JIA) and whether the immune response to vaccinations may be hampered by immunosuppressive therapy for the underlying disease. In this multicenter cohort study, 234 patients with JIA

  9. Brazilian avian metapneumovirus subtypes A and B: experimental infection of broilers and evaluation of vaccine efficacy

    Directory of Open Access Journals (Sweden)

    Márcia B. dos Santos

    2012-12-01

    Full Text Available Avian metapneumovirus (aMPV is a respiratory pathogen associated with the swollen head syndrome (SHS in chickens. In Brazil, live aMPV vaccines are currently used, but subtypes A and, mainly subtype B (aMPV/A and aMPV/B are still circulating. This study was conducted to characterize two Brazilian aMPV isolates (A and B subtypes of chicken origin. A challenge trial to explore the replication ability of the Brazilian subtypes A and B in chickens was performed. Subsequently, virological protection provided from an aMPV/B vaccine against the same isolates was analyzed. Upon challenge experiment, it was shown by virus isolation and real time PCR that aMPV/B could be detected longer and in higher amounts than aMPV/A. For the protection study, 18 one-day-old chicks were vaccinated and challenged at 21 days of age. Using virus isolation and real time PCR, no aMPV/A was detected in the vaccinated chickens, whereas one vaccinated chicken challenged with the aMPV/B isolate was positive. The results showed that aMPV/B vaccine provided a complete heterologous virological protection, although homologous protection was not complete in one chicken. Although only one aMPV/B positive chicken was detected after homologous vaccination, replication in vaccinated animals might allow the emergence of escape mutants.

  10. Balancing safety, efficacy and cost: Improving rotavirus vaccine adoption in low- and middle-income countries

    Directory of Open Access Journals (Sweden)

    Anant Bhan

    2011-12-01

    Full Text Available Diarrheal disease caused by rotavirus claims approximately 500 000 lives each year, mostly in low-income countries. Many of these deaths are preventable through the use of available rotavirus vaccines. Yet, in spite of a WHO recommendation that these vaccines be adopted into all national immunization programs, only a few countries have done so.

  11. Comparison of the protective efficacy of recombinant pseudorabies viruses against pseudorabies and classical swine fever in pigs,, influence of different promoters on gene expression and on protection

    NARCIS (Netherlands)

    Hooft, van B.J.L.; Wind, de N.; Wensvoort, G.; Kimman, T.G.; Gielkens, A.L.J.; Moormann, R.J.M.

    1996-01-01

    The glycoprotein E (gE) locus in the genome of pseudorabies virus (PRV) was used as an insertion site for the expression of glycoprotein E1 of classical swine fever virus (CSFV). Transcription of E1 in the recombinants M401, M402 or M403 was regulated by the gD promoter of PRV, the immediate early

  12. Clinical Efficacy, Safety, and Immunogenicity of a Live Attenuated Tetravalent Dengue Vaccine (CYD-TDV in Children: A Systematic Review with Meta-analysis

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    Moffat Malisheni

    2017-08-01

    Full Text Available BackgroundDengue hemorrhagic fever is the leading cause of hospitalization and death in children living in Asia and Latin America. There is an urgent need for an effective and safe dengue vaccine to reduce morbidity and mortality in this high-risk population given the lack of dengue specific treatment at present. This review aims to determine the efficacy, safety, and immunogenicity of CYD-TDV vaccine in children.MethodsThis is a systematic review including meta-analysis of randomized controlled clinical trial data from Embase, Medline, the Cochrane Library, Web of Science, and ClinicalTrials.gov. Studies that assessed CYD-TDV vaccine efficacy [(1 − RR*100], safety (RR, and immunogenicity (weighted mean difference in children were included in this study. Random effects model was employed to analyze patient-level data extracted from primary studies.ResultsThe overall efficacy of CYD-TDV vaccine was 54% (40–64, while serotype-specific efficacy was 77% (66–85 for DENV4, 75% (65–82 for DENV3, 50% (36–61 for DENV1, and 34% (14–49 for DENV2. 15% (−174–74 vaccine efficacy was obtained for the unknown serotype. Meta-analysis of included studies with longer follow-up time (25 months revealed that CYD-TDV vaccine significantly increased the risk of injection site reactions (RR = 1.1: 1.04–1.17; p-value = 0.001. Immunogenicity (expressed as geometric mean titers in descending order was 439.7 (331.7–547.7, 323 (247 – 398.7, 144.1 (117.9–170.2, and 105 (88.7–122.8 for DENV3, DENV2, DENV1, and DENV4, respectively.ConclusionCYD-TDV vaccine is effective and immunogenic in children overall. Reduced efficacy of CYD-TDV vaccine against DENV2 notoriously known for causing severe dengue infection and dengue outbreaks cause for serious concern. Post hoc meta-analysis of long-term follow-up data (≥25 months from children previously vaccinated with CYD-TDV vaccine is needed to make a conclusion regarding CYD-TDV vaccine

  13. Juvenile-specific cathepsin proteases in Fasciola spp.: their characteristics and vaccine efficacies.

    Science.gov (United States)

    Meemon, Krai; Sobhon, Prasert

    2015-08-01

    Fasciolosis, caused by Fasciola hepatica and Fasciola gigantica, is one of the most neglected tropical zoonotic diseases. One sustainable control strategy against these infections is the employment of vaccines that target proteins essential for parasites' invasion and nutrition acquiring processes. Cathepsin proteases are the most abundantly expressed proteins in Fasciola spp. that have been tested successfully as vaccines against fasciolosis in experimental as well as large animals because of their important roles in digestion of nutrients, invasion, and migration. Specifically, juvenile-specific cathepsin proteases are the more effective vaccines because they could block the invasion and migration of juvenile parasites whose immune evasion mechanism has not yet been fully developed. Moreover, because of high sequence similarity and identity of cathepsins from juveniles with those of adults, the vaccines can attack both the juvenile and adult stages. In this article, the characteristics and vaccine potentials of juvenile-specific cathepsins, i.e., cathepsins L and B, of Fasciola spp. were reviewed.

  14. Enhanced Efficacy of a Codon-Optimized DNA Vaccine Encoding the Glycoprotein Precursor Gene of Lassa Virus in a Guinea Pig Disease Model When Delivered by Dermal Electroporation

    Directory of Open Access Journals (Sweden)

    Niranjan Y. Sardesai

    2013-07-01

    Full Text Available Lassa virus (LASV causes a severe, often fatal, hemorrhagic fever endemic to West Africa. Presently, there are no FDA-licensed medical countermeasures for this disease. In a pilot study, we constructed a DNA vaccine (pLASV-GPC that expressed the LASV glycoprotein precursor gene (GPC. This plasmid was used to vaccinate guinea pigs (GPs using intramuscular electroporation as the delivery platform. Vaccinated GPs were protected from lethal infection (5/6 with LASV compared to the controls. However, vaccinated GPs experienced transient viremia after challenge, although lower than the mock-vaccinated controls. In a follow-on study, we developed a new device that allowed for both the vaccine and electroporation pulse to be delivered to the dermis. We also codon-optimized the GPC sequence of the vaccine to enhance expression in GPs. Together, these innovations resulted in enhanced efficacy of the vaccine. Unlike the pilot study where neutralizing titers were not detected until after virus challenge, modest neutralizing titers were detected in guinea pigs before challenge, with escalating titers detected after challenge. The vaccinated GPs were never ill and were not viremic at any timepoint. The combination of the codon-optimized vaccine and dermal electroporation delivery is a worthy candidate for further development.

  15. SAFETY AND IMMUNOLOGIC EFFICACY OF COMBINED IMMUNIZATION IN CHILDREN AGED 6—7 YEARS WITH VACCINES FROM THE NATIONAL CALENDAR OF PROPHYLACTICS VACCINES

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    I. V. Konovalov

    2013-01-01

    Full Text Available We estimated the safety of the vaccination for prevention of influenza with Grippol® plus vaccine alongside with vaccination with combined preparations for the prevention of diphtheria and tetanus (Td and measles, rubella, mumps in children aged 6—7 years. We determined that combined immunization with the indicated vaccines proves good tolerability and low reactogenicity. Vaccine Grippol® Plus shows low reactogenicity , high immunologenicity and does not cause cross-suppression of antibodies in co-administration with other vaccines on vaccination calendar. Also concomitant vaccination with Grippol® plus and other vaccines does not inhibit the development of a specific immune response against influenza.

  16. Vaccine-Preventable Disease Photos

    Science.gov (United States)

    ... Work Importance of Vaccines Paying for Vaccines State Immunization Programs Tips for Finding Vaccine Records Trusted Sources of ... efficacy, and use of vaccines within the broad immunization community of patients, parents, healthcare organizations, and government health agencies.

  17. The Type of Growth Medium Affects the Presence of a Mycobacterial Capsule and Is Associated With Differences in Protective Efficacy of BCG Vaccination Against Mycobacterium tuberculosis.

    Science.gov (United States)

    Prados-Rosales, Rafael; Carreño, Leandro J; Weinrick, Brian; Batista-Gonzalez, Ana; Glatman-Freedman, Aarona; Xu, Jiayong; Chan, John; Jacobs, William R; Porcelli, Steven A; Casadevall, Arturo

    2016-08-01

    Bacillus Calmette-Guerin (BCG) vaccine is widely used for the prevention of tuberculosis, despite limited efficacy. Most immunological studies of BCG or Mycobacterium tuberculosis strains grow bacteria in the presence of detergent, which also strips the mycobacterial capsule. The impact of the capsule on vaccine efficacy has not been explored. We tested the influence of detergent in cultures of BCG and M. tuberculosis strains on the outcome of vaccination experiments on mice and transcriptional responses on M. tuberculosis  Vaccination of mice with encapsulated BCG promoted a more potent immune response relative to vaccination with unencapsulated BCG, including higher polysaccharide-specific capsule antibody titers, higher interferon γ and interleukin 17 splenic responses, and more multifunctional CD4(+) T cells. These differences correlated with variability in the bacterial burden in lung and spleen of mice infected with encapsulated or unencapsulated M. tuberculosis The combination of vaccination and challenge with encapsulated strains resulted in the greatest protection efficacy. The transcriptome of encapsulated M. tuberculosis was similar to that of starvation, hypoxia, stationary phase, or nonreplicating persistence. The presence of detergent in growth media and a capsule on BCG were associated with differences in the outcome of vaccination, implying that these are important variables in immunological studies. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  18. Entrapment of H1N1 Influenza Virus Derived Conserved Peptides in PLGA Nanoparticles Enhances T Cell Response and Vaccine Efficacy in Pigs.

    Science.gov (United States)

    Hiremath, Jagadish; Kang, Kyung-il; Xia, Ming; Elaish, Mohamed; Binjawadagi, Basavaraj; Ouyang, Kang; Dhakal, Santosh; Arcos, Jesus; Torrelles, Jordi B; Jiang, X; Lee, Chang Won; Renukaradhya, Gourapura J

    2016-01-01

    Pigs are believed to be one of the important sources of emerging human and swine influenza viruses (SwIV). Influenza virus conserved peptides have the potential to elicit cross-protective immune response, but without the help of potent adjuvant and delivery system they are poorly immunogenic. Biodegradable polylactic-co-glycolic acid (PLGA) nanoparticle (PLGA-NP) based vaccine delivery system enhances cross-presentation of antigens by the professional antigen presenting cells. In this study, Norovirus P particle containing SwIV M2e (extracellular domain of the matrix protein 2) chimera and highly conserved two each of H1N1 peptides of pandemic 2009 and classical human influenza viruses were entrapped in PLGA-NPs. Influenza antibody-free pigs were vaccinated with PLGA-NPs peptides cocktail vaccine twice with or without an adjuvant, Mycobacterium vaccae whole cell lysate, intranasally as mist. Vaccinated pigs were challenged with a virulent heterologous zoonotic SwIV H1N1, and one week later euthanized and the lung samples were analyzed for the specific immune response and viral load. Clinically, pigs vaccinated with PLGA-NP peptides vaccine had no fever and flu symptoms, and the replicating challenged SwIV was undetectable in the bronchoalveolar lavage fluid. Immunologically, PLGA-NP peptides vaccination (without adjuvant) significantly increased the frequency of antigen-specific IFNγ secreting CD4 and CD8 T cells response in the lung lymphocytes, despite not boosting the antibody response both at pre- and post-challenge. In summary, our data indicated that nanoparticle-mediated delivery of conserved H1N1 influenza peptides induced the virus specific T cell response in the lungs and reduced the challenged heterologous virus load in the airways of pigs.

  19. Entrapment of H1N1 Influenza Virus Derived Conserved Peptides in PLGA Nanoparticles Enhances T Cell Response and Vaccine Efficacy in Pigs.

    Directory of Open Access Journals (Sweden)

    Jagadish Hiremath

    Full Text Available Pigs are believed to be one of the important sources of emerging human and swine influenza viruses (SwIV. Influenza virus conserved peptides have the potential to elicit cross-protective immune response, but without the help of potent adjuvant and delivery system they are poorly immunogenic. Biodegradable polylactic-co-glycolic acid (PLGA nanoparticle (PLGA-NP based vaccine delivery system enhances cross-presentation of antigens by the professional antigen presenting cells. In this study, Norovirus P particle containing SwIV M2e (extracellular domain of the matrix protein 2 chimera and highly conserved two each of H1N1 peptides of pandemic 2009 and classical human influenza viruses were entrapped in PLGA-NPs. Influenza antibody-free pigs were vaccinated with PLGA-NPs peptides cocktail vaccine twice with or without an adjuvant, Mycobacterium vaccae whole cell lysate, intranasally as mist. Vaccinated pigs were challenged with a virulent heterologous zoonotic SwIV H1N1, and one week later euthanized and the lung samples were analyzed for the specific immune response and viral load. Clinically, pigs vaccinated with PLGA-NP peptides vaccine had no fever and flu symptoms, and the replicating challenged SwIV was undetectable in the bronchoalveolar lavage fluid. Immunologically, PLGA-NP peptides vaccination (without adjuvant significantly increased the frequency of antigen-specific IFNγ secreting CD4 and CD8 T cells response in the lung lymphocytes, despite not boosting the antibody response both at pre- and post-challenge. In summary, our data indicated that nanoparticle-mediated delivery of conserved H1N1 influenza peptides induced the virus specific T cell response in the lungs and reduced the challenged heterologous virus load in the airways of pigs.

  20. Efficacy of a Human Papillomavirus Vaccination Educational Platform in a Diverse Urban Population.

    Science.gov (United States)

    Weinstein, Jacqueline E; Ananth, Ashwin; Brunner, Jacob P; Nelson, Ryan E; Bateman, Marjorie E; Carter, John M; Buell, Joseph F; Friedlander, Paul L

    2016-06-01

    Human papillomavirus (HPV) is a preventable disease that plays a causative role in a significant proportion of malignant neoplasms of the head and neck. Inner-city populations are at risk for HPV-related oropharyngeal cancer, are least likely to receive HPV vaccination, and report a lack of information regarding HPV. To determine whether an educational platform affects knowledge, attitudes, and practices regarding HPV vaccination in an inner-city community. This prospective cohort study, conducted from March 1 to December 31, 2014, surveyed 128 participants at multiple inner-city community centers regarding their knowledge of, attitudes toward, and practices regarding HPV vaccination before and after a brief educational presentation. No eligible individuals refused to participate in the educational session. Surveys were excluded from analysis if they were incomplete. Participants completed two 20-question surveys separated by a 15-minute educational session on HPV-related disease, including a short PowerPoint presentation. Presence of statistically significant differences in survey scores before and after the educational session. Eighty-six participants met eligibility criteria (61 male [70.9%]; 68 with a high school education [79.1%]). Baseline knowledge of HPV, its causal association with cancer, and the existence of a vaccine against HPV were poor: of a total composite score of 20, the mean knowledge score before the educational session was 9.69. Participants' self-rated knowledge regarding HPV disease and vaccination improved significantly as a result of the educational session; the absolute increase in mean knowledge composite score from before the educational session to after the session was 3.52 (17.6%) (95% CI, -2.87 to 9.92; P government involvement in vaccination did not change as a result of the educational session (composite attitudes score before the educational session, 16.57 of 28; score after the session, 15.22; P = .98). Participants' intent

  1. Field Efficacy of an Attenuated Infectious Bronchitis Variant 2 Virus Vaccine in Commercial Broiler Chickens

    Directory of Open Access Journals (Sweden)

    Mohamed A. Elhady

    2018-05-01

    Full Text Available Egyptian poultry suffer from frequent respiratory disease outbreaks associated with Infectious Bronchitis Virus (IBV variant 2 strains (Egy/VarII. Different vaccination programs using imported vaccines have failed to protect the flocks from field challenge. Recent studies confirmed a successful protection using homologous strains as live attenuated vaccines. In this study, a newly developed live attenuated IB-VAR2 vaccine representing the GI-23 Middle East IBV lineage was evaluated in day-old commercial broilers in an IBV-endemic area. A commercial broiler flock was vaccinated with the IB-VAR2 vaccine at day-old age followed by IB-H120 at day 16. The vaccinated flock was monitored on a weekly basis till the slaughter age. The health status and growth performance were monitored, and selected viral pathogen real-time RT-PCR (rRT-PCR detection was conducted on a weekly basis. Finally, the flock was compared to a nearby farm with only the classical IB-H120 vaccination program. Results showed that the IB-VAR2 vaccine was tolerable in day-old broiler chicks. The IBV virus rRT-PCR detection was limited to the trachea as compared to its nephropathogenic parent virus. Respiratory disease problems and high mortalities were reported in the IB-H120-only vaccinated flock. An exposure to a wild-type Egy/VarII strain was confirmed in both flocks as indicated by partial IBV S1 gene sequence. Even though the IB-VAR2-vaccinated flock performance was better than the flock that received only IB-H120, the IBV ELISA (enzyme-linked immunosorbent assay and log2 Haemagglutination inhibition (HI antibody mean titers remained high (3128 ± 2713 and ≥9 log2, respectively until the 28th day of age. The current study demonstrates the safety and effectiveness of IB-VAR2 as a live attenuated vaccine in day-old commercial broilers. Also, the combination of IB-VAR2 and classical IBV vaccines confers a broader protective immune response against IBV in endemic areas.

  2. Deletion of the thymidine kinase gene induces complete attenuation of the Georgia isolate of African swine fever virus

    Science.gov (United States)

    African swine fever virus (ASFV) is the etiological agent of a contagious and often lethal viral disease of domestic pigs. There are no vaccines to control Africa swine fever (ASF). Experimental vaccines have been developed using genetically modified live attenuated ASFVs obtained by specifically de...

  3. Combined administration of synthetic RNA and a conventional vaccine improves immune responses and protection against foot-and-mouth disease virus in swine.

    Science.gov (United States)

    Borrego, Belén; Blanco, Esther; Rodríguez Pulido, Miguel; Mateos, Francisco; Lorenzo, Gema; Cardillo, Sabrina; Smitsaart, Eliana; Sobrino, Francisco; Sáiz, Margarita

    2017-06-01

    Foot-and-mouth disease virus (FMDV) is the causative agent of a highly contagious disease and a major concern in animal health worldwide. We have previously reported the use of RNA transcripts mimicking structural domains in the non-coding regions of the FMDV RNA as potent type-I interferon (IFN) inducers showing antiviral effect in vivo, as well as their immunomodulatory properties in combination with an FMD vaccine in mice. Here, we describe the enhancing effect of RNA delivery on the immunogenicity and protection induced by a suboptimal dose of a conventional FMD vaccine in pigs. Animals receiving the RNA developed earlier and higher levels of neutralizing antibodies against homologous and heterologous isolates, compared to those immunized with the vaccine alone, and had higher anti-FMDV titers at late times post-vaccination. RNA delivery also induced higher specific T-cell response and protection levels against FMDV challenge. Peripheral blood mononuclear cells from pigs inoculated with RNA and the vaccine had a higher IFN-γ specific response than those from pigs receiving the vaccine alone. When challenged with FMDV, all three animals immunized with the conventional vaccine developed antibodies to the non-structural viral proteins 3ABC and two of them developed severe signs of disease. In the group receiving the vaccine together with the RNA, two pigs were fully protected while one showed delayed and mild signs of disease. Our results support the immunomodulatory effect of these RNA molecules in natural hosts and suggest their potential use for improvement of FMD vaccines strategies. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Resource Use and Costs of Dengue: Analysis of Data from Phase III Efficacy Studies of a Tetravalent Dengue Vaccine.

    Science.gov (United States)

    El Fezzazi, Hanna; Branchu, Marie; Carrasquilla, Gabriel; Pitisuttithum, Punnee; Perroud, Ana Paula; Frago, Carina; Coudeville, Laurent

    2017-12-01

    A tetravalent dengue vaccine (CYD-TDV) has recently been approved in 12 countries in southeast Asia and Latin America for individuals aged 9-45 years or 9-60 years (age indication approvals vary by country) living in endemic areas. Data on utilization of medical and nonmedical resources as well as time lost from school and work were collected during the active phase of two phase III efficacy studies performed in 10 countries in the Asia-Pacific region and Latin America (NCT01373281; NCT01374516). We compared dengue-related resource utilization and costs among vaccinated and nonvaccinated participants. Country-specific unit costs were derived from available literature. There were 901 virologically confirmed dengue episodes among participants aged ≥ 9 years ( N = 25,826): corresponding to 373 episodes in the CYD-TDV group ( N = 17,230) and 528 episodes in the control group ( N = 8,596). Fewer episodes in the CYD-TDV group resulted in hospitalization than in the control group (7.0% versus 13.3%; P = 0.002), but both had a similar average length of stay of 4 days. Overall, a two-thirds reduction in resource consumption and missed school/work days was observed in the CYD-TDV group relative to the control group. The estimated direct and indirect cost (2014 I$) associated with dengue episodes per participant in the CYD-TDV group was 73% lower than in the control group (I$6.72 versus I$25.08); representing a saving of I$I8.36 (95% confidence interval [CI]:17.05-19.78) per participant with vaccination. This is the first study providing information on dengue costs among vaccinated individuals and direct confirmation that vaccination has the potential to reduce dengue illness costs.

  5. Efficacy of vaccination at 4 and 6 weeks in the control of canine parvovirus.

    Science.gov (United States)

    De Cramer, K G M; Stylianides, E; van Vuuren, M

    2011-04-21

    Seroconversion after early vaccination at four weeks against canine parvovirus (CPV) using a high antigen titre vaccine was evaluated in 121 puppies from three breeds of dogs housed in kennels representative of the private practitioner's environment. The trial included 52 German shepherd pups, 25 Rottweiler pups and 44 Boerboel pups. From each group 11, 4, and 18 puppies acted as control dogs, respectively. Depending on the different groups, puppies were vaccinated at 4, 6, 9 and 12 weeks. The experimental group differed from the control group in that they received the high titre vaccine at 4 weeks of age, whereas the control group was not vaccinated at 4 weeks. Blood was collected from all pups prior to vaccination to measure maternally derived colostral antibody. The results indicated that vaccination at 4 weeks of age in pups with high maternally derived antibody levels, results in seroconversion rates that may lead to a reduction in the window of susceptibility with respect to CPV infection. The implications of the findings with respect to dogs in heavily contaminated environments are discussed. Copyright © 2010 Elsevier B.V. All rights reserved.

  6. Development and efficacy of an attenuated Vibrio harveyi vaccine candidate with cross protectivity against Vibrio alginolyticus.

    Science.gov (United States)

    Hu, Yong-hua; Deng, Tian; Sun, Bo-guang; Sun, Li

    2012-06-01

    Vibrio harveyi is a Gram-negative bacterial pathogen that can infect a wide range of marine animals. In previous studies, we have reported a virulent V. harveyi strain, T4D. In the present study, an attenuated mutant of T4D, T4DM, was obtained by selection of rifampicin resistance. Compared to the wild type, T4DM was different in whole-cell protein profile and much slower in growth rate when cultured in stress conditions caused by iron depletion. Virulence analysis showed that compared to T4D, T4DM exhibited a dramatically increased median lethal dose, impaired tissue dissemination capacity, defective hemolytic activity, and significantly reduced resistance against the killing effect of host serum. To examine the potential of T4DM as a live attenuated vaccine, Japanese flounder (Paralichthys olivaceus) were vaccinated with T4DM via intraperitoneal injection or immersion. The results showed that at one and two months post-vaccination, fish administered with T4DM via both approaches, in particular that of immersion, were effectively protected against not only V. harveyi but also Vibrio alginolyticus, another important fish pathogen. Microbiological analysis showed that following immersion vaccination, T4DM was recovered from the internal organs of the vaccinated fish in a time-dependent manner within the first 6 days post-vaccination. Serum antibodies against V. harveyi and V. alginolyticus were detected in T4DM-vaccinated fish, and, compared to serum from control fish, serum from T4DM-vaccinated fish was significantly enhanced in bactericidal activity. These results indicate that T4DM is an attenuated strain with residual infectivity and that T4DM can induce effective cross-species protection against both V. harveyi and V. alginolyticus when used as a live immersion vaccine. Copyright © 2012 Elsevier Ltd. All rights reserved.

  7. Protective efficacy of standard Edmonston-Zagreb measles vaccination in infants aged 4.5 months: interim analysis of a randomised clinical trial.

    Science.gov (United States)

    Martins, Cesário L; Garly, May-Lill; Balé, Carlito; Rodrigues, Amabelia; Ravn, Henrik; Whittle, Hilton C; Lisse, Ida M; Aaby, Peter

    2008-07-24

    To examine the protective efficacy of measles vaccination in infants in a low income country before 9 months of age. Randomised clinical trial. 1333 infants aged 4.5 months: 441 in treatment group and 892 in control group. Urban area in Guinea-Bissau. Measles vaccination using standard titre Edmonston-Zagreb vaccine at 4.5 months of age. Vaccine efficacy against measles infection, admission to hospital for measles, and measles mortality before standard vaccination at 9 months of age. 28% of the children tested at 4.5 months of age had protective levels of maternal antibodies against measles at enrolment. After early vaccination against measles 92% had measles antibodies at 9 months of age. A measles outbreak offered a unique situation for testing the efficacy of early measles vaccination. During the outbreak, 96 children developed measles; 19% of unvaccinated children had measles before 9 months of age. The monthly incidence of measles among the 441 children enrolled in the treatment arm was 0.7% and among the 892 enrolled in the control arm was 3.1%. Early vaccination with the Edmonston-Zagreb measles vaccine prevented infection; vaccine efficacy for children with serologically confirmed measles and definite clinical measles was 94% (95% confidence interval 77% to 99%), for admissions to hospital for measles was 100% (46% to 100%), and for measles mortality was 100% (-42% to 100%). The number needed to treat to prevent one case of measles between ages 4.5 months and 9 months during the epidemic was 7.2 (6.8 to 9.2). The treatment group tended to have lower overall mortality (mortality rate ratio 0.18, 0.02 to 1.36) although this was not significant. In low income countries, maternal antibody levels against measles may be low and severe outbreaks of measles can occur in infants before the recommended age of vaccination at 9 months. Outbreaks of measles may be curtailed by measles vaccination using the Edmonston-Zagreb vaccine as early as 4.5 months of age. TRIAL

  8. Recombinant gp350 vaccine for infectious mononucleosis: a phase 2, randomized, double-blind, placebo-controlled trial to evaluate the safety, immunogenicity, and efficacy of an Epstein-Barr virus vaccine in healthy young adults.

    Science.gov (United States)

    Sokal, Etienne M; Hoppenbrouwers, Karel; Vandermeulen, Corinne; Moutschen, Michel; Léonard, Philippe; Moreels, Andre; Haumont, Michèle; Bollen, Alex; Smets, Françoise; Denis, Martine

    2007-12-15

    To date, there is no commercially available vaccine to prevent infectious mononucleosis, a disease frequently induced by Epstein-Barr virus (EBV) infection in adolescents or adults devoid of preexisting immunity to the virus. A total of 181 EBV-seronegative, healthy, young adult volunteers were randomized in a double-blind fashion to receive either placebo or a recombinant EBV subunit glycoprotein 350 (gp350)/aluminum hydroxide and 3-O-desacyl-4'-monophosphoryl lipid A (AS04) candidate vaccine in a 3-dose regimen. The vaccine had demonstrable efficacy (mean efficacy rate, 78.0% [95% confidence interval {CI}, 1.0%-96.0%]) in preventing the development of infectious mononucleosis induced by EBV infection, but it had no efficacy in preventing asymptomatic EBV infection. One month after receipt of the final dose of gp350 vaccine, 98.7% of subjects showed seroconversion to anti-gp350 antibodies (95% CI, 85.5%-97.9%), and they remained anti-gp350 antibody positive for >18 months. Furthermore, there were no concerns regarding the safety or reactogenicity of the gp350/AS04 vaccine. These data support the clinical feasibility of using an EBV vaccine to prevent infectious mononucleosis. ClinicalTrials.gov identifier: NCT00430534.

  9. Development of Mycoplasma hyopneumoniae Recombinant Vaccines.

    Science.gov (United States)

    Marchioro, Silvana Beutinger; Simionatto, Simone; Dellagostin, Odir

    2016-01-01

    Mycoplasma hyopneumoniae is the etiological agent of swine enzootic pneumonia (EP), a disease that affects swine production worldwide. Vaccination is the most cost-effective strategy for the control and prevention of the disease. Research using genome-based approach has the potential to elucidate the biology and pathogenesis of M. hyopneumoniae and contribute to the development of more effective vaccines. Here, we describe the protocol for developing M. hyopneumoniae recombinant vaccines using reverse vaccinology approaches.

  10. Likely Correlation between Sources of Information and Acceptability of A/H1N1 Swine-Origin Influenza Virus Vaccine in Marseille, France

    Science.gov (United States)

    Ninove, Laetitia; Sartor, Catherine; Badiaga, Sékéné; Botelho, Elizabeth; Brouqui, Philippe; Zandotti, Christine; De Lamballerie, Xavier; La Scola, Bernard; Drancourt, Michel; Gould, Ernest A.; Charrel, Rémi N.; Raoult, Didier

    2010-01-01

    Background In France, there was a reluctance to accept vaccination against the A/H1N1 pandemic influenza virus despite government recommendation and investment in the vaccine programme. Methods and Findings We examined the willingness of different populations to accept A/H1N1vaccination (i) in a French hospital among 3315 employees immunized either by in-house medical personnel or mobile teams of MDs and (ii) in a shelter housing 250 homeless persons. Google was used to assess the volume of enquiries concerning incidence of influenza. We analyzed the information on vaccination provided by Google, the website of the major French newspapers, and PubMed. Two trust Surveys were used to assess public opinion on the trustworthiness of people in different professions. Paramedics were significantly more reluctant to accept immunisation than qualified medical staff. Acceptance was significantly increased when recommended directly by MDs. Anecdotal cases of directly observed severe infections were followed by enhanced acceptance of paramedical staff. Scientific literature was significantly more in favour of vaccination than Google and French newspaper websites. In the case of the newspaper websites, information correlated with their recognised political reputations, although they would presumably claim independence from political bias. The Trust Surveys showed that politicians were highly distrusted in contrast with doctors and pharmacists who were considered much more trustworthy. Conclusions The low uptake of the vaccine could reflect failure to convey high quality medical information and advice relating to the benefits of being vaccinated. We believe that the media and internet contributed to this problem by raising concerns within the general population and that failure to involve GPs in the control programme may have been a mistake. GPs are highly regarded by the public and can provide face-to-face professional advice and information. The top-down strategy of vaccine

  11. Conditions Influencing the Efficacy of Vaccination with Live Organisms against Leishmania major Infection

    Science.gov (United States)

    Tabbara, Khaled S.; Peters, Nathan C.; Afrin, Farhat; Mendez, Susana; Bertholet, Sylvie; Belkaid, Yasmine; Sacks, David L.

    2005-01-01

    Numerous experimental vaccines have been developed with the goal of generating long-term cell-mediated immunity to the obligate intracellular parasite Leishmania major, yet inoculation with live, wild-type L. major remains the only successful vaccine in humans. We examined the expression of immunity at the site of secondary, low-dose challenge in the ear dermis to determine the kinetics of parasite clearance and the early events associated with the protection conferred by vaccination with live L. major organisms in C57BL/6 mice. Particular attention was given to the route of vaccination. We observed that the rapidity, strength, and durability of the memory response following subcutaneous vaccination with live parasites in the footpad are even greater than previously appreciated. Antigen-specific gamma interferon (IFN-γ)-producing T cells infiltrate the secondary site by 1.5 weeks, and viable parasites are cleared as early as 2.5 weeks following rechallenge, followed by a rapid drop in IFN-γ+ CD4+ cell numbers in the site. In comparison, intradermal vaccination with live parasites in the ear generates immunity that is delayed in effector cell recruitment to the rechallenge site and in the clearance of parasites from the site. This compromised immunity was associated with a rapid recruitment of interleukin-10 (IL-10)-producing CD4+ T cells to the rechallenge site. Treatment with anti-IL-10-receptor or anti-CD25 antibody enhanced early parasite clearance in ear-vaccinated mice, indicating that chronic infection in the skin generates a population of regulatory cells capable of influencing the level of resistance to reinfection. A delicate balance of effector and regulatory T cells may be required to optimize the potency and durability of vaccines against Leishmaniasis and other intracellular pathogens. PMID:16040984

  12. Safety and efficacy of a xenogeneic DNA vaccine encoding for human tyrosinase as adjunctive treatment for oral malignant melanoma in dogs following surgical excision of the primary tumor.

    Science.gov (United States)

    Grosenbaugh, Deborah A; Leard, A Timothy; Bergman, Philip J; Klein, Mary K; Meleo, Karri; Susaneck, Steven; Hess, Paul R; Jankowski, Monika K; Jones, Pamela D; Leibman, Nicole F; Johnson, Maribeth H; Kurzman, Ilene D; Wolchok, Jedd D

    2011-12-01

    To evaluate the safety and efficacy of a vaccine containing plasmid DNA with an insert encoding human tyrosinase (ie, huTyr vaccine) as adjunctive treatment for oral malignant melanoma (MM) in dogs. 111 dogs (58 prospectively enrolled in a multicenter clinical trial and 53 historical controls) with stage II or III oral MM (modified World Health Organization staging scale, I to IV) in which locoregional disease control was achieved. 58 dogs received an initial series of 4 injections of huTyr vaccine (102 μg of DNA/injection) administered transdermally by use of a needle-free IM vaccination device. Dogs were monitored for adverse reactions. Surviving dogs received booster injections at 6-month intervals thereafter. Survival time for vaccinates was compared with that of historical control dogs via Kaplan-Meier survival analysis for the outcome of death. Kaplan-Meier analysis of survival time until death attributable to MM was determined to be significantly improved for dogs that received the huTyr vaccine, compared with that of historical controls. However, median survival time could not be determined for vaccinates because dogs as adjunctive treatment for oral MM. Response to DNA vaccination in dogs with oral MM may be useful in development of plasmid DNA vaccination protocols for human patients with similar disease.

  13. Rotavirus vaccines

    Science.gov (United States)

    Yen, Catherine; Tate, Jacqueline E; Hyde, Terri B; Cortese, Margaret M; Lopman, Benjamin A; Jiang, Baoming; Glass, Roger I; Parashar, Umesh D

    2014-01-01

    Rotavirus is the leading cause of severe diarrhea among children rotavirus vaccines have been efficacious and effective, with many countries reporting substantial declines in diarrheal and rotavirus-specific morbidity and mortality. However, the full public health impact of these vaccines has not been realized. Most countries, including those with the highest disease burden, have not yet introduced rotavirus vaccines into their national immunization programs. Research activities that may help inform vaccine introduction decisions include (1) establishing effectiveness, impact, and safety for rotavirus vaccines in low-income settings; (2) identifying potential strategies to improve performance of oral rotavirus vaccines in developing countries, such as zinc supplementation; and (3) pursuing alternate approaches to oral vaccines, such as parenteral immunization. Policy- and program-level barriers, such as financial implications of new vaccine introductions, should be addressed to ensure that countries are able to make informed decisions regarding rotavirus vaccine introduction. PMID:24755452

  14. Preclinical efficacy and safety of an anti-IL-1β vaccine for the treatment of type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Gunther Spohn

    2014-01-01

    Full Text Available Neutralization of the inflammatory cytokine interleukin-1β (IL-1β is a promising new strategy to prevent the β-cell destruction, which leads to type 2 diabetes. Here, we describe the preclinical development of a therapeutic vaccine against IL-1β consisting of a detoxified version of IL-1β chemically cross-linked to virus-like particles of the bacteriophage Qβ. The vaccine was well tolerated and induced robust antibody responses in mice, which neutralized the biological activity of IL-1β, as shown both in cellular assays and in challenge experiments in vivo. Antibody titers were long lasting but reversible over time and not associated with the development of potentially harmful T cell responses against IL-1β. Neutralization of IL-1β by vaccine-induced antibodies had no influence on the immune responses of mice to Listeria monocytogenes and Mycobacterium tuberculosis. In a diet-induced model of type 2 diabetes, immunized mice showed improved glucose tolerance, which was mediated by improved insulin secretion by pancreatic β-cells. Hence, immunization with IL-1β conjugated to virus-like particles has the potential to become a safe, efficacious, and cost-effective therapy for the prevention and long-term treatment of type 2 diabetes.

  15. Preclinical efficacy and safety of an anti-IL-1β vaccine for the treatment of type 2 diabetes

    Science.gov (United States)

    Spohn, Gunther; Schori, Christian; Keller, Iris; Sladko, Katja; Sina, Christina; Guler, Reto; Schwarz, Katrin; Johansen, Pål; Jennings, Gary T; Bachmann, Martin F

    2014-01-01

    Neutralization of the inflammatory cytokine interleukin-1β (IL-1β) is a promising new strategy to prevent the β-cell destruction, which leads to type 2 diabetes. Here, we describe the preclinical development of a therapeutic vaccine against IL-1β consisting of a detoxified version of IL-1β chemically cross-linked to virus-like particles of the bacteriophage Qβ. The vaccine was well tolerated and induced robust antibody responses in mice, which neutralized the biological activity of IL-1β, as shown both in cellular assays and in challenge experiments in vivo. Antibody titers were long lasting but reversible over time and not associated with the development of potentially harmful T cell responses against IL-1β. Neutralization of IL-1β by vaccine-induced antibodies had no influence on the immune responses of mice to Listeria monocytogenes and Mycobacterium tuberculosis. In a diet-induced model of type 2 diabetes, immunized mice showed improved glucose tolerance, which was mediated by improved insulin secretion by pancreatic β-cells. Hence, immunization with IL-1β conjugated to virus-like particles has the potential to become a safe, efficacious, and cost-effective therapy for the prevention and long-term treatment of type 2 diabetes. PMID:26015986

  16. "cART intensification by the HIV-1 Tat B clade vaccine: progress to phase III efficacy studies".

    Science.gov (United States)

    Cafaro, Aurelio; Sgadari, Cecilia; Picconi, Orietta; Tripiciano, Antonella; Moretti, Sonia; Francavilla, Vittorio; Pavone Cossut, Maria Rosaria; Buttò, Stefano; Cozzone, Giovanni; Ensoli, Fabrizio; Monini, Paolo; Ensoli, Barbara

    2018-02-01

    In spite of its success at suppressing HIV replication, combination antiretroviral therapy (cART) only partially reduces immune dysregulation and loss of immune functions. These cART-unmet needs appear to be due to persistent virus replication and cell-to-cell transmission in reservoirs, and are causes of increased patients' morbidity and mortality. Up to now, therapeutic interventions aimed at cART-intensification by attacking the virus reservoir have failed. Areas covered: We briefly review the rationale and clinical development of Tat therapeutic vaccine in cART-treated subjects in Italy and South Africa (SA). Vaccination with clade-B Tat induced cross-clade neutralizing antibodies, immune restoration, including CD4 + T cell increase particularly in low immunological responders, and reduction of proviral DNA. Phase III efficacy trials in SA are planned both in adult and pediatric populations. Expert commentary: We propose the Tat therapeutic vaccine as a pathogenesis-driven intervention that effectively intensifies cART and may lead to a functional cure and provide new perspectives for prevention and virus eradication strategies.

  17. Guillain-Barré Syndrome (GBS) and Flu Vaccine

    Science.gov (United States)

    ... Swine Variant Pandemic Other Guillain-Barré syndrome and Flu Vaccine Questions & Answers Language: English (US) Español Recommend ... it among people who have been vaccinated against flu? The background rate for GBS in the Unites ...

  18. Vector optimization and needle-free intradermal application of a broadly protective polyvalent influenza A DNA vaccine for pigs and humans

    DEFF Research Database (Denmark)

    Borggren, Marie; Nielsen, Jens; Bragstad, Karoline

    2015-01-01

    such as the induction of cellular and humoral immunity, inherent safety and rapid production time. We have previously developed a DNA vaccine encoding selected influenza proteins of pandemic origin and demonstrated broad protective immune responses in ferrets and pigs. In this study, we evaluated our DNA vaccine......The threat posed by the 2009 pandemic H1N1 virus emphasized the need for new influenza A virus vaccines inducing a broad cross-protective immune response for use in both humans and pigs. An effective and broad influenza vaccine for pigs would greatly benefit the pork industry and contribute...... to public health by diminishing the risk of emerging highly pathogenic reassortants. Current inactivated protein vaccines against swine influenza produce only short-lived immunity and have no efficacy against heterologous strains. DNA vaccines are a potential alternative with advantages...

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

    Directory of Open Access Journals (Sweden)

    Shufang Fan

    2009-05-01

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

  20. Longitudinal study to assess the safety and efficacy of a live-attenuated SHIV vaccine in long term immunized rhesus macaques

    International Nuclear Information System (INIS)

    Yankee, Thomas M.; Sheffer, Darlene; Liu Zhengian; Dhillon, Sukhbir; Jia Fenglan; Chebloune, Yahia; Stephens, Edward B.; Narayan, Opendra

    2009-01-01

    Live-attenuated viruses derived from SIV and SHIV have provided the most consistent protection against challenge with pathogenic viruses, but concerns regarding their long-term safety and efficacy have hampered their clinical usefulness. We report a longitudinal study in which we evaluated the long-term safety and efficacy of ΔvpuSHIV PPC , a live virus vaccine derived from SHIV PPC . Macaques were administered two inoculations of ΔvpuSHIV PPC , three years apart, and followed for eight years. None of the five vaccinated macaques developed an AIDS-like disease from the vaccine. At eight years, macaques were challenged with pathogenic SIV and SHIV. None of the four macaques with detectable cellular-mediated immunity prior to challenge had detectable viral RNA in the plasma. This study demonstrates that multiple inoculations of a live vaccine virus can be used safely and can significantly extend the efficacy of the vaccine, as compared to a single inoculation, which is efficacious for approximately three years

  1. Potentiating Effects of MPL on DSPC Bearing Cationic Liposomes Promote Recombinant GP63 Vaccine Efficacy: High Immunogenicity and Protection

    Science.gov (United States)

    Mazumder, Saumyabrata; Maji, Mithun; Ali, Nahid

    2011-01-01

    Background Vaccines that activate strong specific Th1-predominant immune responses are critically needed for many intracellular pathogens, including Leishmania. The requirement for sustained and efficient vaccination against leishmaniasis is to formulate the best combination of immunopotentiating adjuvant with the stable antigen (Ag) delivery system. The aim of the present study is to evaluate the effectiveness of an immunomodulator on liposomal Ag through subcutaneous (s.c.) route of immunization, and its usefulness during prime/boost against visceral leishmaniasis (VL) in BALB/c mice. Methodology/Principal Findings Towards this goal, we formulated recombinant GP63 (rGP63)-based vaccines either with monophosphoryl lipid A-trehalose dicorynomycolate (MPL-TDM) or entrapped within cationic liposomes or both. Combinatorial administration of liposomes with MPL-TDM during prime confers activation of dendritic cells, and induces an early robust T cell response. To investigate whether the combined formulation is required for optimum immune response during boost as well, we chose to evaluate the vaccine efficacy in mice primed with combined adjuvant system followed by boosting with either rGP63 alone, in association with MPL-TDM, liposomes or both. We provide evidences that the presence of either liposomal rGP63 or combined formulations during boost is necessary for effective Th1 immune responses (IFN-γ, IL-12, NO) before challenge infection. However, boosting with MPL-TDM in conjugation with liposomal rGP63 resulted in a greater number of IFN-γ producing effector T cells, significantly higher levels of splenocyte proliferation, and Th1 responses compared to mice boosted with liposomal rGP63, after virulent Leishmania donovani (L. donovani) challenge. Moreover, combined formulations offered superior protection against intracellular amastigote replication in macrophages in vitro, and hepatic and splenic parasite load in vivo. Conclusion Our results define the

  2. Non-invasive monitoring of Streptococcus pyogenes vaccine efficacy using biophotonic imaging.

    Directory of Open Access Journals (Sweden)

    Faraz M Alam

    Full Text Available Streptococcus pyogenes infection of the nasopharynx represents a key step in the pathogenic cycle of this organism and a major focus for vaccine development, requiring robust models to facilitate the screening of potentially protective antigens. One antigen that may be an important target for vaccination is the chemokine protease, SpyCEP, which is cell surface-associated and plays a role in pathogenesis. Biophotonic imaging (BPI can non-invasively characterize the spatial location and abundance of bioluminescent bacteria in vivo. We have developed a bioluminescent derivative of a pharyngeal S. pyogenes strain by transformation of an emm75 clinical isolate with the luxABCDE operon. Evaluation of isogenic recombinant strains in vitro and in vivo confirmed that bioluminescence conferred a growth deficit that manifests as a fitness cost during infection. Notwithstanding this, bioluminescence expression permitted non-invasive longitudinal quantitation of S. pyogenes within the murine nasopharynx albeit with a detection limit corresponding to approximately 10(5 bacterial colony forming units (CFU in this region. Vaccination of mice with heat killed streptococci, or with SpyCEP led to a specific IgG response in the serum. BPI demonstrated that both vaccine candidates reduced S. pyogenes bioluminescence emission over the course of nasopharyngeal infection. The work suggests the potential for BPI to be used in the non-invasive longitudinal evaluation of potential S. pyogenes vaccines.

  3. Improving immunogenicity and efficacy of vaccines for genital herpes containing herpes simplex virus glycoprotein D.

    Science.gov (United States)

    Awasthi, Sita; Shaw, Carolyn; Friedman, Harvey

    2014-12-01

    No vaccines are approved for prevention or treatment of genital herpes. The focus of genital herpes vaccine trials has been on prevention using herpes simplex virus type 2 (HSV-2) glycoprotein D (gD2) alone or combined with glycoprotein B. These prevention trials did not achieve their primary end points. However, subset analyses reported some positive outcomes in each study. The most recent trial was the Herpevac Trial for Women that used gD2 with monophosphoryl lipid A and alum as adjuvants in herpes simplex virus type 1 (HSV-1) and HSV-2 seronegative women. Unexpectedly, the vaccine prevented genital disease by HSV-1 but not HSV-2. Currently, HSV-1 causes more first episodes of genital herpes than HSV-2, highlighting the importance of protecting against HSV-1. The scientific community is conflicted between abandoning vaccine efforts that include gD2 and building upon the partial successes of previous trials. We favor building upon success and present approaches to improve outcomes of gD2-based subunit antigen vaccines.

  4. Likely correlation between sources of information and acceptability of A/H1N1 swine-origin influenza virus vaccine in Marseille, France.

    Directory of Open Access Journals (Sweden)

    Antoine Nougairède

    Full Text Available BACKGROUND: In France, there was a reluctance to accept vaccination against the A/H1N1 pandemic influenza virus despite government recommendation and investment in the vaccine programme. METHODS AND FINDINGS: We examined the willingness of different populations to accept A/H1N1 vaccination (i in a French hospital among 3315 employees immunized either by in-house medical personnel or mobile teams of MDs and (ii in a shelter housing 250 homeless persons. Google was used to assess the volume of enquiries concerning incidence of influenza. We analyzed the information on vaccination provided by Google, the website of the major French newspapers, and PubMed. Two trust Surveys were used to assess public opinion on the trustworthiness of people in different professions. Paramedics were significantly more reluctant to accept immunisation than qualified medical staff. Acceptance was significantly increased when recommended directly by MDs. Anecdotal cases of directly observed severe infections were followed by enhanced acceptance of paramedical staff. Scientific literature was significantly more in favour of vaccination than Google and French newspaper websites. In the case of the newspaper websites, information correlated with their recognised political reputations, although they would presumably claim independence from political bias. The Trust Surveys showed that politicians were highly dis-trusted in contrast with doctors and pharmacists who were considered much more trustworthy. CONCLUSIONS: The low uptake of the vaccine could reflect failure to convey high quality medical information and advice relating to the benefits of being vaccinated. We believe that the media and internet contributed to this problem by raising concerns within the general population and that failure to involve GPs in the control programme may have been a mistake. GPs are highly regarded by the public and can provide face-to-face professional advice and information. The top

  5. Efficacy of two H5N9-inactivated vaccines against challenge with a recent H5N1 highly pathogenic avian influenza isolate from a chicken in Thailand.

    Science.gov (United States)

    Bublot, Michel; Le Gros, François-Xavier; Nieddu, Daniela; Pritchard, Nikki; Mickle, Thomas R; Swayne, David E

    2007-03-01

    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.

  6. Study of the safety, immunogenicity and efficacy of attenuated and killed Leishmania (Leishmania major vaccines in a rhesus monkey (Macaca mulatta model of the human disease

    Directory of Open Access Journals (Sweden)

    VF Amaral

    2002-10-01

    Full Text Available We have compared the efficacy of two Leishmania (Leishmania major vaccines, one genetically attenuated (DHFR-TS deficient organisms, the other inactivated [autoclaved promastigotes (ALM with bacillus Calmete-Guérin (BCG], in protecting rhesus macaques (Macaca mulatta against infection with virulent L. (L. major. Positive antigen-specific recall proliferative response was observed in vaccinees (79% in attenuated parasite-vaccinated monkeys, versus 75% in ALM-plus-BCG-vaccinated animals, although none of these animals exhibited either augmented in vitro gamma interferon (IFN-g production or positive delayed-type hypersensitivity (DTH response to the leishmanin skin test prior to the challenge. Following challenge, there were significant differences in blastogenic responses (p < 0.05 between attenuated-vaccinated monkeys and naïve controls. In both vaccinated groups very low levels of antibody were found before challenge, which increased after infective challenge. Protective immunity did not follow vaccination, in that monkeys exhibited skin lesion at the site of challenge in all the groups. The most striking result was the lack of pathogenicity of the attenuated parasite, which persisted in infected animals for up to three months, but were incapable of causing disease under the conditions employed. We concluded that both vaccine protocols used in this study are safe in primates, but require further improvement for vaccine application.

  7. Pilot scale production of highly efficacious and stable enterovirus 71 vaccine candidates.

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    Ai-Hsiang Chou

    Full Text Available BACKGROUND: Enterovirus 71 (EV71 has caused several epidemics of hand, foot and mouth diseases (HFMD in Asia and now is being recognized as an important neurotropic virus. Effective medications and prophylactic vaccine against EV71 infection are urgently needed. Based on the success of inactivated poliovirus vaccine, a prototype chemically inactivated EV71 vaccine candidate has been developed and currently in human phase 1 clinical trial. PRINCIPAL FINDING: In this report, we present the development of a serum-free cell-based EV71 vaccine. The optimization at each step of the manufacturing process was investigated, characterized and quantified. In the up-stream process development, different commercially available cell culture media either containing serum or serum-free was screened for cell growth and virus yield using the roller-bottle technology. VP-SFM serum-free medium was selected based on the Vero cell growth profile and EV71 virus production. After the up-stream processes (virus harvest, diafiltration and concentration, a combination of gel-filtration liquid chromatography and/or sucrose-gradient ultracentrifugation down-stream purification processes were investigated at a pilot scale of 40 liters each. Although the combination of chromatography and sucrose-gradient ultracentrifugation produced extremely pure EV71 infectious virus particles, the overall yield of vaccine was 7-10% as determined by a VP2-based quantitative ELISA. Using chromatography as the downstream purification, the virus yield was 30-43%. To retain the integrity of virus neutralization epitopes and the stability of the vaccine product, the best virus inactivation was found to be 0.025% formalin-treatment at 37 °C for 3 to 6 days. Furthermore, the formalin-inactivated virion vaccine candidate was found to be stable for >18 months at 4 °C and a microgram of viral proteins formulated with alum adjuvant could induce strong virus-neutralizing antibody responses in mice

  8. Pilot scale production of highly efficacious and stable enterovirus 71 vaccine candidates.

    Science.gov (United States)

    Chou, Ai-Hsiang; Liu, Chia-Chyi; Chang, Cheng-Peng; Guo, Meng-Shin; Hsieh, Shih-Yang; Yang, Wen-Hsueh; Chao, Hsin-Ju; Wu, Chien-Long; Huang, Ju-Lan; Lee, Min-Shi; Hu, Alan Yung-Chi; Lin, Sue-Chen; Huang, Yu-Yun; Hu, Mei-Hua; Chow, Yen-Hung; Chiang, Jen-Ron; Chang, Jui-Yuan; Chong, Pele

    2012-01-01

    Enterovirus 71 (EV71) has caused several epidemics of hand, foot and mouth diseases (HFMD) in Asia and now is being recognized as an important neurotropic virus. Effective medications and prophylactic vaccine against EV71 infection are urgently needed. Based on the success of inactivated poliovirus vaccine, a prototype chemically inactivated EV71 vaccine candidate has been developed and currently in human phase 1 clinical trial. In this report, we present the development of a serum-free cell-based EV71 vaccine. The optimization at each step of the manufacturing process was investigated, characterized and quantified. In the up-stream process development, different commercially available cell culture media either containing serum or serum-free was screened for cell growth and virus yield using the roller-bottle technology. VP-SFM serum-free medium was selected based on the Vero cell growth profile and EV71 virus production. After the up-stream processes (virus harvest, diafiltration and concentration), a combination of gel-filtration liquid chromatography and/or sucrose-gradient ultracentrifugation down-stream purification processes were investigated at a pilot scale of 40 liters each. Although the combination of chromatography and sucrose-gradient ultracentrifugation produced extremely pure EV71 infectious virus particles, the overall yield of vaccine was 7-10% as determined by a VP2-based quantitative ELISA. Using chromatography as the downstream purification, the virus yield was 30-43%. To retain the integrity of virus neutralization epitopes and the stability of the vaccine product, the best virus inactivation was found to be 0.025% formalin-treatment at 37 °C for 3 to 6 days. Furthermore, the formalin-inactivated virion vaccine candidate was found to be stable for >18 months at 4 °C and a microgram of viral proteins formulated with alum adjuvant could induce strong virus-neutralizing antibody responses in mice, rats, rabbits, and non-human primates. These

  9. Efficacy, safety and immunogenicity of a human rotavirus vaccine (RIX4414) in Hong Kong children up to three years of age: a randomized, controlled trial.

    Science.gov (United States)

    Lau, Yu-Lung; Nelson, E Anthony S; Poon, Kin-Hung; Chan, Paul K S; Chiu, Susan; Sung, Rita; Leung, Chi Wai; Ng, Daniel; Ma, Yee Man; Chan, Desmond; Lee, Tsz Leung; Tang, Joyce; Kwan, Yat Wah; Ip, Patricia; Ho, Marco; Fung, Lai-Wah Eva; Tang, Haiwen; Suryakiran, P V; Han, Htay Htay; Bock, Hans

    2013-04-26

    A phase III, double-blind, randomized, controlled trial was conducted in Hong Kong to evaluate the efficacy, safety and immunogenicity of a human rotavirus vaccine, RIX4414 (Rotarix) against severe rotavirus gastroenteritis in children up to three years of age. Healthy infants aged 6-12 weeks were enrolled between 08-December-2003 and 31-August-2005 and received two oral doses of either RIX4414 vaccine (N=1513) or placebo (N=1512) given 2 months apart. Vaccine efficacy was assessed from two weeks post-Dose 2 until the children were two and three years of age. Anti-rotavirus IgA seroconversion rate was calculated pre-vaccination and 1-2 months post-Dose 2 using ELISA (cut-off=20 U/mL) for 100 infants. Safety was assessed until the children were two years of age; serious adverse events (SAEs) were recorded throughout the study period. In children aged two and three years of life, vaccine efficacy against severe rotavirus gastroenteritis was 95.6% (95% CI: 73.1%-99.9%) and 96.1% (95% CI: 76.5%-99.9%), respectively. The seroconversion rate 1-2 months after the second dose of RIX4414 was 97.5% (95% CI: 86.8%-99.9%). At least one SAE was recorded in 439 and 477 infants who were administered RIX4414 and placebo, respectively (p-value=0.130). Six intussusception cases were reported (RIX4414=4; placebo=2) and none was assessed to be vaccine-related. RIX4414 was efficacious, immunogenic and safe in the prevention of rotavirus gastroenteritis for at least two years post-vaccination in Hong Kong children. Copyright © 2013 Elsevier Ltd. All rights reserved.

  10. Efficacy of an Adenovirus-based Anti-cocaine Vaccine to Reduce Cocaine Self-administration and Reacqusition using a Choice Procedure in Rhesus Macaques

    Science.gov (United States)

    Evans, Suzette M.; Foltin, Richard W.; Hicks, Martin J.; Rosenberg, Jonathan B.; De, Bishnu P.; Janda, Kim D.; Kaminsky, Stephen M.; Crystal, Ronald G.

    2016-01-01

    Immunopharmacotherapy offers an approach for treating cocaine abuse by specifically targeting the cocaine molecule and preventing its access to the CNS. dAd5GNE is a novel cocaine vaccine that attenuates the stimulant and the reinforcing effects of cocaine in rats. The goal of this study was to extend and validate dAd5GNE vaccine efficacy in non-human primates. Six experimentally naïve adult female rhesus monkeys (Macaca mulatta) were trained to self-administer 0.1 mg/kg/injection intravenous (i.v.) cocaine or receive candy; then 4 monkeys were administered the vaccine and 2 monkeys were administered vehicle intramuscularly, with additional vaccine boosts throughout the study. The reinforcing effects of cocaine were measured during self-administration, extinction, and reacquisition (relapse) phases. Serum antibody titers in the vaccinated monkeys remained high throughout the study. There was no change in the preference for cocaine over candy over a 20-week period in 5 of the 6 monkeys; only one of the 4 (25%) vaccinated monkeys showed a decrease in cocaine choice. All 6 monkeys extinguished responding for cocaine during saline extinction testing; vaccinated monkeys tended to take longer to extinguish responding than control monkeys (17.5 vs. 7.0 sessions). Vaccination substantially retarded reacquisition of cocaine self-administration; control monkeys resumed cocaine self-administration within 6–41 sessions and 1 vaccinated monkey resumed cocaine self-administration in 19 sessions. The other 3 vaccinated monkeys required between 57–94 sessions to resume cocaine self-administration even in the context of employing several manipulations to encourage cocaine reacquisition. These data suggest that the dAdGNE vaccine may have therapeutic potential for humans who achieve cocaine abstinence as part of a relapse prevention strategy. PMID:27697554

  11. Characterization and protective efficacy in an animal model of a novel truncated rotavirus VP8 subunit parenteral vaccine candidate.

    Science.gov (United States)

    Xue, Miaoge; Yu, Linqi; Che, Yaojian; Lin, Haijun; Zeng, Yuanjun; Fang, Mujin; Li, Tingdong; Ge, Shengxiang; Xia, Ningshao

    2015-05-21

    The cell-attachment protein VP8* of rotavirus is a potential candidate parenteral vaccine. However, the yield of full-length VP8 protein (VP8*, residues 1-231) expressed in Escherichia coli was low, and a truncated VP8 protein (ΔVP8*, residues 65-231) cannot elicit efficient protective immunity in a mouse model. In this study, tow novel truncated VP8 proteins, VP8-1 (residues 26-231) and VP8-2 (residues 51-231), were expressed in E. coli and evaluated for immunogenicity and protective efficacy, compared with VP8* and ΔVP8*. As well as ΔVP8*, the protein VP8-1 and VP8-2 were successfully expressed in high yield and purified in homogeneous dimeric forms, while the protein VP8* was expressed with lower yield and prone to aggregation and degradation in solution. Although the immunogenicity of the protein VP8*, VP8-1, VP8-2 and ΔVP8* was comparable, immunization of VP8* and VP8-1 elicited significantly higher neutralizing antibody titers than that of VP8-2 and ΔVP8* in mice. Furthermore, when assessed using a mouse maternal antibody model, the efficacy of VP8-1 to protect against rotavirus-induced diarrhea in pups was comparable to that of VP8*, both were dramatically higher than that of VP8-2 and ΔVP8*. Taken together, the novel truncated protein VP8-1, with increased yield, improved homogeneity and high protective efficacy, is a viable candidate for further development of a parenterally administrated prophylactic vaccine against rotavirus infection. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Efficacy and safety of pentavalent rotavirus vaccine in Japan: a randomized, double-blind, placebo-controlled, multicenter trial.

    Science.gov (United States)

    Iwata, Satoshi; Nakata, Shuji; Ukae, Susumu; Koizumi, Yoshitugu; Morita, Yasuyuki; Kuroki, Haruo; Tanaka, Yoshiyuki; Shizuya, Toshiyuki; Schödel, Florian; Brown, Michelle L; Lawrence, Jody

    2013-08-01

    Rotavirus is the most common cause of severe gastroenteritis in children under 5 y of age. Estimates of disease burden in Japan suggest that between 26,500 and 78,000 children in this age group need hospitalization each year, resulting in a direct medical cost of 10 to 24 billion Yen. Since being introduced in routine infant immunization schedules in the United States in 2006, the oral live pentavalent rotavirus vaccine RV5 (RotaTeq™) has contributed to dramatic reductions in the incidence of rotavirus gastroenteritis (RVGE) and in health care resource utilization. This was a multicenter, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of a 3-dose regimen of RV5 in healthy infants, age 6 to 12 weeks, at 32 sites across Japan. The results indicate that RV5 was significantly efficacious in preventing any severity [74.5% (95% confidence interval [CI]: 39.9%, 90.6%; pvaccine. The observed cases of RVGE included rotavirus types G1 (n=19), G3 (n=9), G9 (n=5) and one unspecified G serotype with P1A[8]. No G2 or G4 RVGE cases were observed, and this study was not powered to evaluate efficacy against individual serotypes. RV5 was generally safe and well tolerated in Japanese infants. These results are comparable to those observed in clinical studies conducted in other developed countries. Introduction of the vaccine in Japan may reduce disease burden and associated health care costs.

  13. 76 FR 79203 - Prospective Grant of Exclusive License: Avian Influenza Vaccines for Domesticated Poultry/Wild...

    Science.gov (United States)

    2011-12-21

    ... Exclusive License: Avian Influenza Vaccines for Domesticated Poultry/Wild Birds To Be Provided to the... serotypes H5N1, H1N1, H3N2, and H3N8 for poultry, swine and equine. Particularly one vaccine, a trivalent... influenza vaccines are specifically designed for poultry, swine and equine recipients, with the following...

  14. Immunological efficacy of Vaccination against Measles in Children with Down syndrome

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    S. P. Kaplina

    2011-01-01

    Full Text Available The data of current vaccination process of cellular, humoral immunity and specific antibody formation in 41 children with Down syndrome at the age of 1 year to 6 years old is observed. To prevent easles used measles vaccine (n=12, divaccine -measles-mumps (n=21 and or Priorix vaccine (n=8. The comparison group consisted of 63 children without Down syndrome. The post-vaccination period in 97,6% of children with Down syndrome cases are asymptomatic, only 2,4% of children mentioned layering of intercurrent diseases. The immunological status in children with Down syndrome is characterized by a significant decrease in the  umber leucocytes, lymphocytes, CD3+, CD4+, CD8+ and absolute number of CD20+, but functional activity of the cells is preserved. By 30 days after immunization they have increased leucocytes, lymphocytes, CD 95+cells. The number of antibodies significantly increased (6,63±0,33 compared to 5,79±0,32 log2, р < 0,05.

  15. Evaluation of efficacy of LaSota ® vaccine against circulating ...

    African Journals Online (AJOL)

    Groups III and IV were vaccinated once through oral and ocular routes, respectively, at the age of 10 days. Group V served as a negative control. Immune response against NDV was measured by the level of antibodies using Haemagglutination Inhibition (HI) test and resistance to challenge with virulent strain of NDV.

  16. Genetically modified vaccines augment the efficacy of cancer surgery and chemotherapy

    Czech Academy of Sciences Publication Activity Database

    Bubeník, Jan

    2009-01-01

    Roč. 55, č. 6 (2009), s. 199-200 ISSN 0015-5500 Institutional research plan: CEZ:AV0Z50520514 Keywords : genetically modified vaccines * cancer surgery and chemotherapy Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 0.924, year: 2009

  17. Analysis of V2 antibody responses induced in vaccinees in the ALVAC/AIDSVAX HIV-1 vaccine efficacy trial.

    Directory of Open Access Journals (Sweden)

    Susan Zolla-Pazner

    Full Text Available The RV144 clinical trial of a prime/boost immunizing regimen using recombinant canary pox (ALVAC-HIV and two gp120 proteins (AIDSVAX B and E was previously shown to have a 31.2% efficacy rate. Plasma specimens from vaccine and placebo recipients were used in an extensive set of assays to identify correlates of HIV-1 infection risk. Of six primary variables that were studied, only one displayed a significant inverse correlation with risk of infection: the antibody (Ab response to a fusion protein containing the V1 and V2 regions of gp120 (gp70-V1V2. This finding prompted a thorough examination of the results generated with the complete panel of 13 assays measuring various V2 Abs in the stored plasma used in the initial pilot studies and those used in the subsequent case-control study. The studies revealed that the ALVAC-HIV/AIDSVAX vaccine induced V2-specific Abs that cross-react with multiple HIV-1 subgroups and recognize both conformational and linear epitopes. The conformational epitope was present on gp70-V1V2, while the predominant linear V2 epitope mapped to residues 165-178, immediately N-terminal to the putative α4β7 binding motif in the mid-loop region of V2. Odds ratios (ORs were calculated to compare the risk of infection with data from 12 V2 assays, and in 11 of these, the ORs were ≤1, reaching statistical significance for two of the variables: Ab responses to gp70-V1V2 and to overlapping V2 linear peptides. It remains to be determined whether anti-V2 Ab responses were directly responsible for the reduced infection rate in RV144 and whether anti-V2 Abs will prove to be important with other candidate HIV vaccines that show efficacy, however, the results support continued dissection of Ab responses to the V2 region which may illuminate mechanisms of protection from HIV-1 infection and may facilitate the development of an effective HIV-1 vaccine.

  18. Shikonin enhances efficacy of a gene-based cancer vaccine via induction of RANTES

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    Chen Hui-Ming

    2012-04-01

    Full Text Available Abstract Background Shikonin, a phytochemical purified from Lithospermum erythrorhizon, has been shown to confer diverse pharmacological activities, including accelerating granuloma formation, wound healing, anti-inflammation and others, and is explored for immune-modifier activities for vaccination in this study. Transdermal gene-based vaccine is an attractive approach for delivery of DNA transgenes encoding specific tumor antigens to host skin tissues. Skin dendritic cells (DCs, a potent antigen-presenting cell type, is known to play a critical role in transmitting and orchestrating tumor antigen-specific immunities against cancers. The present study hence employs these various components for experimentation. Method The mRNA and protein expression of RANTES were detected by RT-PCR and ELISA, respectively. The regional expression of RANTES and tissue damage in test skin were evaluated via immunohistochemistry assay. Fluorescein isothiocyanate sensitization assay was performed to trace the trafficking of DCs from the skin vaccination site to draining lymph nodes. Adjuvantic effect of shikonin on gene gun-delivered human gp100 (hgp100 DNA cancer vaccine was studied in a human gp100-transfected B16 (B16/hgp100 tumor model. Results Among various phytochemicals tested, shikonin induced the highest level of expression of RANTES in normal skin tissues. In comparison, mouse RANTES cDNA gene transfection induced a higher level of mRANTES expression for a longer period, but caused more extensive skin damage. Topical application of shikonin onto the immunization site before gene gun-mediated vaccination augmented the population of skin DCs migrating into the draining lymph nodes. A hgp100 cDNA gene vaccination regimen with shikonin pretreatment as an adjuvant in a B16/hgp100 tumor model increased cytotoxic T lymphocyte activities in splenocytes and lymph node cells on target tumor cells. Conclusion Together, our findings suggest that shikonin can

  19. Phase 1/2a Trial of Plasmodium vivax Malaria Vaccine Candidate VMP001/AS01B in Malaria-Naive Adults: Safety, Immunogenicity, and Efficacy.

    Directory of Open Access Journals (Sweden)

    Jason W Bennett

    2016-02-01

    Full Text Available A vaccine to prevent infection and disease caused by Plasmodium vivax is needed both to reduce the morbidity caused by this parasite and as a key component in efforts to eradicate malaria worldwide. Vivax malaria protein 1 (VMP001, a novel chimeric protein that incorporates the amino- and carboxy- terminal regions of the circumsporozoite protein (CSP and a truncated repeat region that contains repeat sequences from both the VK210 (type 1 and the VK247 (type 2 parasites, was developed as a vaccine candidate for global use.We conducted a first-in-human Phase 1 dose escalation vaccine study with controlled human malaria infection (CHMI of VMP001 formulated in the GSK Adjuvant System AS01B. A total of 30 volunteers divided into 3 groups (10 per group were given 3 intramuscular injections of 15 μg, 30 μg, or 60 μg respectively of VMP001, all formulated in 500 μL of AS01B at each immunization. All vaccinated volunteers participated in a P. vivax CHMI 14 days following the third immunization. Six non-vaccinated subjects served as infectivity controls.The vaccine was shown to be well tolerated and immunogenic. All volunteers generated robust humoral and cellular immune responses to the vaccine antigen. Vaccination did not induce sterile protection; however, a small but significant delay in time to parasitemia was seen in 59% of vaccinated subjects compared to the control group. An association was identified between levels of anti-type 1 repeat antibodies and prepatent period.This trial was the first to assess the efficacy of a P. vivax CSP vaccine candidate by CHMI. The association of type 1 repeat-specific antibody responses with delay in the prepatency period suggests that augmenting the immune responses to this domain may improve strain-specific vaccine efficacy. The availability of a P. vivax CHMI model will accelerate the process of P. vivax vaccine development, allowing better selection of candidate vaccines for advancement to field trials.

  20. Efficacy of a 60Co irradiated vaccine for experimentally infected calves with dictyocaulus viviparus

    International Nuclear Information System (INIS)

    Zurita, Edgar; Paredes, Julio; Fernandez, Ardey

    1991-01-01

    Dictyocaulus viviparus larvae in non-infected stage (L.1) were cultured in vitro to their infective stage (L.3) and were irradiated with 40 Krad from 6 0 C o and used as a vaccine. The oral experimental vaccine dose was 1000 L.3/animal. Three groups were formed with 8 calves in each one: group No. 1 and group No. 2 were vaccinated at 10 weeks of age. Four weeks later group No. 1 was infected with non-irradiated 60 L.3/Kg. of animal weight 'challenge dose'. After four weeks of post-vaccination group No. 2 was revaccinated and 4 weeks later it was infected with the 'challenge dose' as the previous group. Eight calves constituted group No. 3, four in each group; they were infected with only the challenge dose respectively. Information data on respiratory and cardiac frequency, temperature, weight, and L.1 count/g. of feces were obtained from each animal three times a week. After five weeks of post-challenge all animals were slaughtered to observe anatomopathologic lessions in the heart and lungs; the number of adult Dictyocaulus viviparus present in the respiratory tract were search 't'. Student test was used for the statistical analysis. The weight increment difference between animals of group No. 1 related control group was 7Kg.; and 11.25 Kg/animal in group No. 2 respectively. The percentage of protection confered by the vaccine to the subjects in group No. 1 relative to the respectivecontrol group, was 83.2; that for the group No. 2 was 88.5 per cent. Post-morten examination revealed severe anatomopathologic lessions in the control groups; only few lessions were observed in group No. 1 and practically none in group No. 2

  1. Coverage, efficacy or dosing interval: which factor predominantly influences the impact of routine childhood vaccination for the prevention of varicella? A model-based study for Italy

    Directory of Open Access Journals (Sweden)

    Katsiaryna Holl

    2016-10-01

    Full Text Available Abstract Background Varicella is a highly infectious disease with a significant public health and economic burden, which can be prevented with childhood routine varicella vaccination. Vaccination strategies differ by country. Some factors are known to play an important role (number of doses, coverage, dosing interval, efficacy and catch-up programmes, however, their relative impact on the reduction of varicella in the population remains unclear. This paper aims to help policy makers prioritise the critical factors to achieve the most successful vaccination programme with the available budget. Methods Scenarios assessed the impact of different vaccination strategies on reduction of varicella disease in the population. A dynamic transmission model was used and adapted to fit Italian demographics and population mixing patterns. Inputs included coverage, number of doses, dosing intervals, first-dose efficacy and availability of catch-up programmes, based on strategies currently used or likely to be used in different countries. The time horizon was 30 years. Results Both one- and two-dose routine varicella vaccination strategies prevented a comparable number of varicella cases with complications, but two-doses provided broader protection due to prevention of a higher number of milder varicella cases. A catch-up programme in susceptible adolescents aged 10–14 years old reduced varicella cases by 27–43 % in older children, which are often more severe than in younger children. Coverage, for all strategies, sustained at high levels achieved the largest reduction in varicella. In general, a 20 % increase in coverage resulted in a further 27–31 % reduction in varicella cases. When high coverage is reached, the impact of dosing interval and first-dose vaccine efficacy had a relatively lower impact on disease prevention in the population. Compared to the long (11 years dosing interval, the short (5 months and medium (5 years interval schedules

  2. Modelling the Growth of Swine Flu

    Science.gov (United States)

    Thomson, Ian

    2010-01-01

    The spread of swine flu has been a cause of great concern globally. With no vaccine developed as yet, (at time of writing in July 2009) and given the fact that modern-day humans can travel speedily across the world, there are fears that this disease may spread out of control. The worst-case scenario would be one of unfettered exponential growth.…

  3. Overexpression of a Mycobacterium ulcerans Ag85B-EsxH Fusion Protein in Recombinant BCG Improves Experimental Buruli Ulcer Vaccine Efficacy.

    Directory of Open Access Journals (Sweden)

    Bryan E Hart

    2016-12-01

    Full Text Available Buruli ulcer (BU vaccine design faces similar challenges to those observed during development of prophylactic tuberculosis treatments. Multiple BU vaccine candidates, based upon Mycobacterium bovis BCG, altered Mycobacterium ulcerans (MU cells, recombinant MU DNA, or MU protein prime-boosts, have shown promise by conferring transient protection to mice against the pathology of MU challenge. Recently, we have shown that a recombinant BCG vaccine expressing MU-Ag85A (BCG MU-Ag85A displayed the highest level of protection to date, by significantly extending the survival time of MU challenged mice compared to BCG vaccination alone. Here we describe the generation, immunogenicity testing, and evaluation of protection conferred by a recombinant BCG strain which overexpresses a fusion of two alternative MU antigens, Ag85B and the MU ortholog of tuberculosis TB10.4, EsxH. Vaccination with BCG MU-Ag85B-EsxH induces proliferation of Ag85 specific CD4+ T cells in greater numbers than BCG or BCG MU-Ag85A and produces IFNγ+ splenocytes responsive to whole MU and recombinant antigens. In addition, anti-Ag85A and Ag85B IgG humoral responses are significantly enhanced after administration of the fusion vaccine compared to BCG or BCG MU-Ag85A. Finally, mice challenged with MU following a single subcutaneous vaccination with BCG MU-Ag85B-EsxH display significantly less bacterial burden at 6 and 12 weeks post-infection, reduced histopathological tissue damage, and significantly longer survival times compared to vaccination with either BCG or BCG MU-Ag85A. These results further support the potential of BCG as a foundation for BU vaccine design, whereby discovery and recombinant expression of novel immunogenic antigens could lead to greater anti-MU efficacy using this highly safe and ubiquitous vaccine.

  4. Field efficacy study of a novel ready-to-use vaccine against mycoplasma hyopneumoniae and porcine circovirus type 2 in a Greek farm.

    Science.gov (United States)

    Tzika, Eleni D; Tassis, Panagiotis D; Koulialis, Dimitrios; Papatsiros, Vassileios G; Nell, Tom; Brellou, Georgia; Tsakmakidis, Ioannis

    2015-01-01

    The primary objective of this study was to assess the efficacy, under field conditions, of a novel ready-to use Mycoplasma hyopneumoniae (M hyo) and Porcine circovirus type 2 (PCV2) combination vaccine given to piglets as one vaccination (1-shot) at 3 weeks of age. The study was carried out according to a controlled, randomised, and blinded design in a Greek pig herd with clinical M. hyo and subclinical PCV2 infection. Moreover, based on serology at the time of vaccination, the average PCV2 titre was 9.15 log 2 and represented the level of maternally derived antibodies (MDA). In total 602 healthy suckling piglets, originating from 4 weekly farrowing batches were allocated randomly, within litters, to one of two groups. The pigs in one group were vaccinated with the test product and the other pigs were injected with saline. Vaccination significantly reduced lesions of craneo-ventral pulmonary consolidation in vaccinated group [expressed as lung lesion score (LLS)] (Mixed model ANOVA: p  < 0.0001). The mean LLS was 17.1 in the controls and 10.6 in the treatment group, respectively. The average daily weight gain (ADWG) during the finishing (54 g better in the treatment group) and whole study period (34 g better in vaccinated animals) was significantly greater in vaccinated than control pigs. The vaccinated pigs had a significant reduction of PCV2 viraemia when compared with the controls. The test product was considered effective in the face of average MDA, based on significantly reduced severity of LLS and PCV2 viral load, as well as improved ADWG in vaccinated versus control pigs.

  5. Oral vaccination of fish

    OpenAIRE

    Embregts, Carmen W.E.; Forlenza, Maria

    2016-01-01

    The limited number of oral vaccines currently approved for use in humans and veterinary species clearly illustrates that development of efficacious and safe oral vaccines has been a challenge not only for fish immunologists. The insufficient efficacy of oral vaccines is partly due to antigen breakdown in the harsh gastric environment, but also to the high tolerogenic gut environment and to inadequate vaccine design. In this review we discuss current approaches used to develop oral vaccines fo...

  6. Efficacy of a Trivalent Hand, Foot, and Mouth Disease Vaccine against Enterovirus 71 and Coxsackieviruses A16 and A6 in Mice

    Directory of Open Access Journals (Sweden)

    Elizabeth A. Caine

    2015-11-01

    Full Text Available Hand, foot, and mouth disease (HFMD has recently emerged as a major public health concern across the Asian-Pacific region. Enterovirus 71 (EV71 and Coxsackievirus A16 (CVA16 are the primary causative agents of HFMD, but other members of the Enterovirus A species, including Coxsackievirus A6 (CVA6, can cause disease. The lack of small animal models for these viruses have hampered the development of a licensed HFMD vaccine or antivirals. We have previously reported on the development of a mouse model for EV71 and demonstrated the protective efficacy of an inactivated EV71 vaccine candidate. Here, mouse-adapted strains of CVA16 and CVA6 were produced by sequential passage of the viruses through mice deficient in interferon (IFN α/β (A129 and α/β and γ (AG129 receptors. Adapted viruses were capable of infecting 3 week-old A129 (CVA6 and 12 week-old AG129 (CVA16 mice. Accordingly, these models were used in active and passive immunization studies to test the efficacy of a trivalent vaccine candidate containing inactivated EV71, CVA16, and CVA6. Full protection from lethal challenge against EV71 and CVA16 was observed in trivalent vaccinated groups. In contrast, monovalent vaccinated groups with non-homologous challenges failed to cross protect. Protection from CVA6 challenge was accomplished through a passive transfer study involving serum raised against the trivalent vaccine. These animal models will be useful for future studies on HFMD related pathogenesis and the efficacy of vaccine candidates.

  7. Efficacy of a Trivalent Hand, Foot, and Mouth Disease Vaccine against Enterovirus 71 and Coxsackieviruses A16 and A6 in Mice.

    Science.gov (United States)

    Caine, Elizabeth A; Fuchs, Jeremy; Das, Subash C; Partidos, Charalambos D; Osorio, Jorge E

    2015-11-17

    Hand, foot, and mouth disease (HFMD) has recently emerged as a major public health concern across the Asian-Pacific region. Enterovirus 71 (EV71) and Coxsackievirus A16 (CVA16) are the primary causative agents of HFMD, but other members of the Enterovirus A species, including Coxsackievirus A6 (CVA6), can cause disease. The lack of small animal models for these viruses have hampered the development of a licensed HFMD vaccine or antivirals. We have previously reported on the development of a mouse model for EV71 and demonstrated the protective efficacy of an inactivated EV71 vaccine candidate. Here, mouse-adapted strains of CVA16 and CVA6 were produced by sequential passage of the viruses through mice deficient in interferon (IFN) α/β (A129) and α/β and γ (AG129) receptors. Adapted viruses were capable of infecting 3 week-old A129 (CVA6) and 12 week-old AG129 (CVA16) mice. Accordingly, these models were used in active and passive immunization studies to test the efficacy of a trivalent vaccine candidate containing inactivated EV71, CVA16, and CVA6. Full protection from lethal challenge against EV71 and CVA16 was observed in trivalent vaccinated groups. In contrast, monovalent vaccinated groups with non-homologous challenges failed to cross protect. Protection from CVA6 challenge was accomplished through a passive transfer study involving serum raised against the trivalent vaccine. These animal models will be useful for future studies on HFMD related pathogenesis and the efficacy of vaccine candidates.

  8. Chimeric classical swine fever (CSF)-Japanese encephalitis (JE) viral replicon as a non-transmissible vaccine candidate against CSF and JE infections.

    Science.gov (United States)

    Yang, Zhenhua; Wu, Rui; Li, Robert W; Li, Ling; Xiong, Zhongliang; Zhao, Haizhong; Guo, Deyin; Pan, Zishu

    2012-04-01

    A trans-complemented chimeric CSF-JE virus replicon was constructed using an infectious cDNA clone of the CSF virus (CSFV) Alfort/187 strain. The CSFV E2 gene was deleted, and a fragment containing the region encoding a truncated envelope protein (tE, amino acid 292-402, domain III) of JE virus (JEV) was inserted into the resultant plasmid, pA187delE2, to generate the recombinant cDNA clone pA187delE2/JEV-tE. Porcine kidney 15 (PK15) cells that constitutively express the CSFV E2p7 proteins were then transfected with in vitro-transcribed RNA from pA187delE2/JEV-tE. As a result, the chimeric CSF-JE virus replicon particle (VRP), rv187delE2/JEV-tE, was rescued. In a mouse model, immunization with the chimeric CSF-JE VRP induced strong production of JEV-specific antibody and conferred protection against a lethal JEV challenge. Pigs immunized with CSF-JE VRP displayed strong anti-CSFV and anti-JEV antibody responses and protection against CSFV and JEV challenge infections. Our evidence suggests that E2-complemented CSF-JE VRP not only has potential as a live-attenuated non-transmissible vaccine candidate against CSF and JE but also serves as a potential DIVA (Differentiating Infected from Vaccinated Animals) vaccine for CSF in pigs. Together, our data suggest that the non-transmissible chimeric VRP expressing foreign antigenic proteins may represent a promising strategy for bivalent DIVA vaccine design. Copyright © 2012 Elsevier B.V. All rights reserved.

  9. Association of TLR7 variants with AIDS-like disease and AIDS vaccine efficacy in rhesus macaques.

    Directory of Open Access Journals (Sweden)

    Roman A Siddiqui

    Full Text Available In HIV infection, TLR7-triggered IFN-α production exerts a direct antiviral effect through the inhibition of viral replication, but may also be involved in immune pathogenesis leading to AIDS. TLR7 could also be an important mediator of vaccine efficacy. In this study, we analyzed polymorphisms in the X-linked TLR7 gene in the rhesus macaque model of AIDS. Upon resequencing of the TLR7 gene in 36 rhesus macaques of Indian origin, 12 polymorphic sites were detected. Next, we identified three tightly linked single nucleotide polymorphisms (SNP as being associated with survival time. Genotyping of 119 untreated, simian immunodeficiency virus (SIV-infected male rhesus macaques, including an 'MHC adjusted' subset, revealed that the three TLR7 SNPs are also significantly associated with set-point viral load. Surprisingly, this effect was not observed in 72 immunized SIV-infected male monkeys. We hypothesize (i that SNP c.13G>A in the leader peptide is causative for the observed genotype-phenotype association and that (ii the underlying mechanism is related to RNA secondary structure formation. Therefore, we investigated a fourth SNP (c.-17C>T, located 17 bp upstream of the ATG translation initiation codon, that is also potentially capable of influencing RNA structure. In c.13A carriers, neither set-point viral load nor survival time were related to the c.-17C>T genotype. In c.13G carriers, by contrast, the c.-17C allele was significantly associated with prolonged survival. Again, no such association was detected among immunized SIV-infected macaques. Our results highlight the dual role of TLR7 in immunodeficiency virus infection and vaccination and imply that it may be important to control human AIDS vaccine trials, not only for MHC genotype, but also for TLR7 genotype.

  10. Immune Suppression in Tumors as a Surmountable Obstacle to Clinical Efficacy of Cancer Vaccines

    International Nuclear Information System (INIS)

    Wieërs, Grégoire; Demotte, Nathalie; Godelaine, Danièle; Bruggen, Pierre van der

    2011-01-01

    Human tumors are usually not spontaneously eliminated by the immune system and therapeutic vaccination of cancer patients with defined antigens is followed by tumor regressions only in a small minority of the patients. The poor vaccination effectiveness could be explained by an immunosuppressive tumor microenvironment. Because T cells that infiltrate tumor metastases have an impaired ability to lyse target cells or to secrete cytokine, many researchers are trying to decipher the underlying immunosuppressive mechanisms. We will review these here, in particular those considered as potential therapeutic targets. A special attention will be given to galectins, a family of carbohydrate binding proteins. These lectins have often been implicated in inflammation and cancer and may be useful targets for the development of new anti-cancer therapies

  11. Randomised, double-blind, safety and efficacy of a killed oral vaccine for enterotoxigenic E. Coli diarrhoea of travellers to Guatemala and Mexico.

    Science.gov (United States)

    Sack, David A; Shimko, Janet; Torres, Olga; Bourgeois, August L; Francia, Domingo Sanchez; Gustafsson, Björn; Kärnell, Anders; Nyquist, Iréne; Svennerholm, Ann-Mari

    2007-05-30

    We tested the efficacy of a killed oral vaccine for enterotoxigenic Escherichia coli (ETEC) diarrhoea to determine if two doses of vaccine with colonization factor antigens (CF) and cholera B subunit would protect against ETEC diarrhoea of travellers. Six hundred seventy-two healthy travellers going to Mexico or Guatemala were studied in a prospective, randomised, placebo-controlled trial. The primary outcome was a vaccine preventable outcome (VPO), defined as an episode of ETEC diarrhoea with an ETEC organism producing heat labile toxin (LT) or CF homologous with the vaccine, without other known causes. The vaccine was safe and stimulated anti-heat labile toxin antibodies. There was a significant decrease in more severe VPO episodes (PE=77%, p=0.039) as defined by symptoms that interfered with daily activities or more than five loose stools in a day, although the total number of VPO events did not differ significantly in the vaccine and placebo groups. We conclude that the new oral ETEC vaccine reduces the rate of more severe episodes of traveller's diarrhoea (TD) due to VPO-ETEC, but it did not reduce the overall rate of ETEC diarrhoea or of travellers' diarrhoea due to other causes.

  12. ChAd63-MVA-vectored blood-stage malaria vaccines targeting MSP1 and AMA1: assessment of efficacy against mosquito bite challenge in humans.

    Science.gov (United States)

    Sheehy, Susanne H; Duncan, Christopher J A; Elias, Sean C; Choudhary, Prateek; Biswas, Sumi; Halstead, Fenella D; Collins, Katharine A; Edwards, Nick J; Douglas, Alexander D; Anagnostou, Nicholas A; Ewer, Katie J; Havelock, Tom; Mahungu, Tabitha; Bliss, Carly M; Miura, Kazutoyo; Poulton, Ian D; Lillie, Patrick J; Antrobus, Richard D; Berrie, Eleanor; Moyle, Sarah; Gantlett, Katherine; Colloca, Stefano; Cortese, Riccardo; Long, Carole A; Sinden, Robert E; Gilbert, Sarah C; Lawrie, Alison M; Doherty, Tom; Faust, Saul N; Nicosia, Alfredo; Hill, Adrian V S; Draper, Simon J

    2012-12-01

    The induction of cellular immunity, in conjunction with antibodies, may be essential for vaccines to protect against blood-stage infection with the human malaria parasite Plasmodium falciparum. We have shown that prime-boost delivery of P. falciparum blood-stage antigens by chimpanzee adenovirus 63 (ChAd63) followed by the attenuated orthopoxvirus MVA is safe and immunogenic in healthy adults. Here, we report on vaccine efficacy against controlled human malaria infection delivered by mosquito bites. The blood-stage malaria vaccines were administered alone, or together (MSP1+AMA1), or with a pre-erythrocytic malaria vaccine candidate (MSP1+ME-TRAP). In this first human use of coadministered ChAd63-MVA regimes, we demonstrate immune interference whereby responses against merozoite surface protein 1 (MSP1) are dominant over apical membrane antigen 1 (AMA1) and ME-TRAP. We also show that induction of strong cellular immunity against MSP1 and AMA1 is safe, but does not impact on parasite growth rates in the blood. In a subset of vaccinated volunteers, a delay in time to diagnosis was observed and sterilizing protection was observed in one volunteer coimmunized with MSP1+AMA1-results consistent with vaccine-induced pre-erythrocytic, rather than blood-stage, immunity. These data call into question the utility of T cell-inducing blood-stage malaria vaccines and suggest that the focus should remain on high-titer antibody induction against susceptible antigen targets.

  13. Sinclair swine melanoma

    International Nuclear Information System (INIS)

    Hook, R.R.; Berkelhammer, J.; Hamby, C.V.

    1986-01-01

    Sinclair(S-1) miniature swine spontaneously develop melanomas which have many biologic and histologic features in common with human superficial spreading melanoma. Host control of this neoplasm was indicated by the high incidence of spontaneous regression, a decrease in tumor development with age and a decrease in progressive growth of the tumor as age of tumor development increases. Immunologic mechanisms were implicated in host control by histologic observation of a mononuclear inflammatory infiltration of tumors which lead to depigmentation and fibrosis. In vitro immunologic studies revealed that leukocytes from melanoma swine were sensitized specifically to a tumor associated antigen like substance present in extracts of cutaneous melanomas and cultured swine melanoma cells and that melanoma swine leukocytes were cytotoxic for swine melanoma cells. Furthermore, these studies suggested the existence of a common cross reactive, melanoma associated antigen shared by human and swine melanomas. Antigenic analyses of swine melanomas with mouse monoclonal antibodies developed to a single swine melanoma cell culture and with rabbit antisera developed to pooled extracts of cutaneous melanomas demonstrated the presence of tumor associated antigens in swine melanoma cell culture and cutaneous melanomas. The failure of mouse monoclonal antibodies to detect antigens in cutaneous melanoma extracts and the failure of rabbit antisera to detect antigens in melanoma cell culture extracts suggested a differential in antigen expression between swine melanoma cells grown in vitro and in vivo

  14. Efficacy of a DNA Vaccine Carrying Eimeria maxima Gam56 Antigen Gene against Coccidiosis in Chickens

    Science.gov (United States)

    Xu, Jinjun; Zhang, Yan

    2013-01-01

    To control coccidiosis without using prophylactic medications, a DNA vaccine targeting the gametophyte antigen Gam56 from Eimeria maxima in chickens was constructed, and the immunogenicity and protective effects were evaluated. The ORF of Gam56 gene was cloned into an eukaryotic expression vector pcDNA3.1(zeo)+. Expression of Gam56 protein in COS-7 cells transfected with recombinant plasmid pcDNA-Gam56 was confirmed by indirect immunofluorescence assay. The DNA vaccine was injected intramuscularly to yellow feathered broilers of 1-week old at 3 dosages (25, 50, and 100 µg/chick). Injection was repeated once 1 week later. One week after the second injection, birds were challenged orally with 5×104 sporulated oocysts of E. maxima, then weighed and killed at day 8 post challenge. Blood samples were collected and examined for specific peripheral blood lymphocyte proliferation activity and serum antibody levels. Compared with control groups, the administration of pcDNA-Gam56 vaccine markedly increased the lymphocyte proliferation activity (P<0.05) at day 7 and 14 after the first immunization. The level of lymphocyte proliferation started to decrease on day 21 after the first immunization. A similar trend was seen in specific antibody levels. Among the 3 pcDNA-Gam56 immunized groups, the median dosage group displayed the highest lymphocyte proliferation and antibody levels (P<0.05). The median dosage group had the greatest relative body weight gain (89.7%), and the greatest oocyst shedding reduction (53.7%). These results indicate that median dosage of DNA vaccine had good immunogenicity and immune protection effects, and may be used in field applications for coccidiosis control. PMID:23710081

  15. Immunotherapeutic efficacy of vaccines generated by fusion of dendritic cells and HPV16-associated tumour cells

    Czech Academy of Sciences Publication Activity Database

    Bubeník, Jan; Šímová, Jana; Bieblová, Jana; Reiniš, Milan; Indrová, Marie

    2005-01-01

    Roč. 16, Suppl. 1 (2005), s. 101 ISSN 1107-3756. [World Congress on Advances in Oncology /10./ and International Symposium on Molecular Medicine /8./. 05.10.13-05.10.15, Hersonissos] R&D Projects: GA ČR(CZ) GA301/04/0492; GA MZd(CZ) NR8004 Institutional research plan: CEZ:AV0Z50520514 Keywords : HPV16 * dendritic cells * vaccines Subject RIV: EC - Immunology

  16. Superior Efficacy of a Human Immunodeficiency Virus Vaccine Combined with Antiretroviral Prevention in Simian-Human Immunodeficiency Virus-Challenged Nonhuman Primates.

    Science.gov (United States)

    Le Grand, Roger; Dereuddre-Bosquet, Nathalie; Dispinseri, Stefania; Gosse, Leslie; Desjardins, Delphine; Shen, Xiaoying; Tolazzi, Monica; Ochsenbauer, Christina; Saidi, Hela; Tomaras, Georgia; Prague, Mélanie; Barnett, Susan W; Thiebaut, Rodolphe; Cope, Alethea; Scarlatti, Gabriella; Shattock, Robin J

    2016-06-01

    increased susceptibility to a simian-HIV vaginal challenge), while the microbicide reduced the infection risk compared to that of vaccinated and naive animals. Importantly, the combined interventions provided the greatest level of protection, which was sustained following withdrawal of the microbicide. The data suggest that provision of ARV prophylaxis during vaccination reduces the potential for unexpected increased risks of infection following immunization and augments vaccine efficacy. These findings are important for the potential adoption of ARV prophylaxis as the baseline intervention for future HIV/AIDS vaccines. Copyright © 2016 Le Grand et al.

  17. Efficacy and safety of vi-tetanus toxoid conjugated typhoid vaccine (PedaTyph™) in Indian children: School based cluster randomized study.

    Science.gov (United States)

    Mitra, Monjori; Shah, Nitin; Ghosh, Apurba; Chatterjee, Suparna; Kaur, Iqbal; Bhattacharya, Nisha; Basu, Suparna

    2016-04-02

    Vi polysaccharide typhoid vaccines cannot be used in children vaccine prepared by binding Vi to tetanus toxoids (Vi-TT) induces protective levels even in children safety following vaccination with a Vi-TT vaccine in children 6 months to 12 years of age. Overall, 1765 subjects were recruited from two registered municipal urban slums of southern Kolkata. Most of the children of the slum dwellers attended the schools in the locality which was selected with permission from the school authority. Schools were randomly divided into vaccinated (Test group) and unvaccinated group (Control group). Children and their siblings of test group received 2-doses of PedaTyph™ vaccine at 6 weeks interval. Control group received vaccines as per national guidelines. Adverse events (AEs) were examined after 30 minutes, 1 month and clinical events were observed till 12 months post-vaccination. Incidence of culture positive typhoid fever in the control group was 1.27% vis-a-vis none in vaccine group during 12 months. In subgroup evaluated for immunogenicity, an antibody titer value of 1.8 EU/ml (95% CI: 1.5 EU/ml, 2.2 EU/ml), 32 EU/ml (95% CI: 27.0 EU/ml, 39.0 EU/ml) and 14 EU/ml (95% CI: 12.0 EU/ml, 17.0 EU/ml) at baseline, 6 weeks and 12 months, respectively was observed. Sero-conversion among the sub-group was 100% after 6 weeks of post-vaccination and 83% after 12 months considering 4-fold rise from baseline. The efficacy of vaccine was 100 % (95% CI: 97.6%, 100%) in the first year of follow-up with minimal AEs post vaccination. Vi conjugate typhoid vaccine conferred 100% protection against typhoid fever in 1765 children 6 months to 12 years of age with high immunogenicity in a subgroup from the vaccine arm.

  18. Evaluation of quadrivalent HPV 6/11/16/18 vaccine efficacy against cervical and anogenital disease in subjects with serological evidence of prior vaccine type HPV infection

    DEFF Research Database (Denmark)

    Olsson, Sven-Eric; Kjaer, Susanne K; Sigurdsson, Kristján

    2009-01-01

    Objective: In the quadrivalent (types 6/11/16/18) HPV vaccine (GARDASIL((R))/SILGARD((R))) clinical program, 73% of women aged 16-26 were naïve to all vaccine HPV types. In these women, prophylactic administration of the vaccine was highly effective in preventing HPV 6/11/16/18-related cervical...

  19. Immuno-efficacy of DNA vaccines encoding PLP1 and ROP18 against experimental Toxoplasma gondii infection in mice.

    Science.gov (United States)

    Chen, Yajun; Yu, Miao; Hemandez, J A; Li, Jiexi; Yuan, Zi-Guo; Yan, Haikuo

    2018-05-01

    We constructed a new plasmid pIRESneo/ROP18/PLP1 that was injected intramuscularly into Kunming mice to evaluate its immune efficacy. The immunized mice exhibited significantly increased serum IgG2a levels, lymphocyte counts and Th1-type cytokine (IL-2, IL-12 and IFN-γ) levels. Moreover, the immunized mice exhibited longer survival times (44.7 ± 2.1 days for ROP18/PLP1 and 47.2 ± 2.9 days for ROP18/PLP1 + IL-18) and lower brain cyst burden (68.9% for ROP18/PLP1 and 72.4% for ROP18/PLP1 + IL-18) than control mice after T. gondii challenge. Our results demonstrate that the multiple-gene DNA vaccine including both ROP18 and PLP1 elicits greater protection against T. gondii challenge and stronger immunogenicity than single-gene vaccines. Copyright © 2018 Elsevier Inc. All rights reserved.

  20. Immunogenicity and protective efficacy of yeast extracts containing rotavirus-like particles: a potential veterinary vaccine.

    Science.gov (United States)

    Rodríguez-Limas, William A; Pastor, Ana Ruth; Esquivel-Soto, Ernesto; Esquivel-Guadarrama, Fernando; Ramírez, Octavio T; Palomares, Laura A

    2014-05-19

    Rotavirus is the most common cause of severe diarrhea in many animal species of economic interest. A simple, safe and cost-effective vaccine is required for the control and prevention of rotavirus in animals. In this study, we evaluated the use of Saccharomyces cerevisiae extracts containing rotavirus-like particles (RLP) as a vaccine candidate in an adult mice model. Two doses of 1mg of yeast extract containing rotavirus proteins (between 0.3 and 3 μg) resulted in an immunological response capable of reducing the replication of rotavirus after infection. Viral shedding in all mice groups diminished in comparison with the control group when challenged with 100 50% diarrhea doses (DD50) of murine rotavirus strain EDIM. Interestingly, when immunizing intranasally protection against rotavirus infection was observed even when no increase in rotavirus-specific antibody titers was evident, suggesting that cellular responses were responsible of protection. Our results indicate that raw yeast extracts containing rotavirus proteins and RLP are a simple, cost-effective alternative for veterinary vaccines against rotavirus. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Short-Term Efficacy of CBD-Enriched Hemp Oil in Girls with Dysautonomic Syndrome after Human Papillomavirus Vaccination.

    Science.gov (United States)

    Palmieri, Beniamino; Laurino, Carmen; Vadalà, Maria

    2017-02-01

    Cannabidiol (CBD)-based treatments for several diseases, including Tourette's syndrome, multiple sclerosis, epilepsy, movement disorders and glaucoma, are proving to be beneficial and the scientific clinical background of the drug is continuously evolving. To investigate the short-term effect of CBD-enriched hemp oil for relieving symptoms and improving the life quality (QOL) in young girls with adverse drug effects (ADRs) following human papillomavirus (HPV) vaccine. In this anecdotal, retrospective, "compassionate-use", observational, open-label study, 12 females (age 12-24 years) with severe somatoform and dysautonomic syndrome following HPV vaccination were given sublingual CBD-rich hemp oil drops, 25 mg/kg per day supplemented by 2-5 mg/ml CBD once a week until a maximum dose of 150 mg/ml CBD per day was reached over a 3 month period. Patients' quality of life was evaluated using the medical outcome short-form health survey questionnaire (SF-36). Two patients dropped out due to iatrogenic adverse events and another two patients stopped the treatment early due to lack of any improvement. SF-36 showed significant benefits in the physical component score (P oil also significantly reduced body pain according to the SF-36 assessment. No significant differences from the start of treatment to several months post-treatment were detected in role limitations due to emotional reactions (P = 0.02). This study demonstrated the safety and tolerability of CBD-rich hemp oil and the primary efficacy endpoint. Randomized controlled trials are warranted to characterize the safety profile and efficacy of this compound.

  2. Mimotope-based vaccines of Leishmania infantum antigens and their protective efficacy against visceral leishmaniasis.

    Directory of Open Access Journals (Sweden)

    Lourena Emanuele Costa

    Full Text Available BACKGROUND: The development of cost-effective prophylactic strategies to prevent leishmaniasis has become a high-priority. The present study has used the phage display technology to identify new immunogens, which were evaluated as vaccines in the murine model of visceral leishmaniasis (VL. Epitope-based immunogens, represented by phage-fused peptides that mimic Leishmania infantum antigens, were selected according to their affinity to antibodies from asymptomatic and symptomatic VL dogs' sera. METHODOLOGY/MAIN FINDINGS: Twenty phage clones were selected after three selection cycles, and were evaluated by means of in vitro assays of the immune stimulation of spleen cells derived from naive and chronically infected with L. infantum BALB/c mice. Clones that were able to induce specific Th1 immune response, represented by high levels of IFN-γ and low levels of IL-4 were selected, and based on their selectivity and specificity, two clones, namely B10 and C01, were further employed in the vaccination protocols. BALB/c mice vaccinated with clones plus saponin showed both a high and specific production of IFN-γ, IL-12, and GM-CSF after in vitro stimulation with individual clones or L. infantum extracts. Additionally, these animals, when compared to control groups (saline, saponin, wild-type phage plus saponin, or non-relevant phage clone plus saponin, showed significant reductions in the parasite burden in the liver, spleen, bone marrow, and paws' draining lymph nodes. Protection was associated with an IL-12-dependent production of IFN-γ, mainly by CD8+ T cells, against parasite proteins. These animals also presented decreased parasite-mediated IL-4 and IL-10 responses, and increased levels of parasite-specific IgG2a antibodies. CONCLUSIONS/SIGNIFICANCE: This study describes two phage clones that mimic L. infantum antigens, which were directly used as immunogens in vaccines and presented Th1-type immune responses, and that significantly reduced the

  3. Efficacy and effectiveness of an rVSV-vectored vaccine in preventing Ebola virus disease: final results from the Guinea ring vaccination, open-label, cluster-randomised trial (Ebola Ça Suffit!).

    Science.gov (United States)

    Henao-Restrepo, Ana Maria; Camacho, Anton; Longini, Ira M; Watson, Conall H; Edmunds, W John; Egger, Matthias; Carroll, Miles W; Dean, Natalie E; Diatta, Ibrahima; Doumbia, Moussa; Draguez, Bertrand; Duraffour, Sophie; Enwere, Godwin; Grais, Rebecca; Gunther, Stephan; Gsell, Pierre-Stéphane; Hossmann, Stefanie; Watle, Sara Viksmoen; Kondé, Mandy Kader; Kéïta, Sakoba; Kone, Souleymane; Kuisma, Eewa; Levine, Myron M; Mandal, Sema; Mauget, Thomas; Norheim, Gunnstein; Riveros, Ximena; Soumah, Aboubacar; Trelle, Sven; Vicari, Andrea S; Røttingen, John-Arne; Kieny, Marie-Paule

    2017-02-04

    rVSV-ZEBOV is a recombinant, replication competent vesicular stomatitis virus-based candidate vaccine expressing a surface glycoprotein of Zaire Ebolavirus. We tested the effect of rVSV-ZEBOV in preventing Ebola virus disease in contacts and contacts of contacts of recently confirmed cases in Guinea, west Africa. We did an open-label, cluster-randomised ring vaccination trial (Ebola ça Suffit!) in the communities of Conakry and eight surrounding prefectures in the Basse-Guinée region of Guinea, and in Tomkolili and Bombali in Sierra Leone. We assessed the efficacy of a single intramuscular dose of rVSV-ZEBOV (2×10 7 plaque-forming units administered in the deltoid muscle) in the prevention of laboratory confirmed Ebola virus disease. After confirmation of a case of Ebola virus disease, we definitively enumerated on a list a ring (cluster) of all their contacts and contacts of contacts including named contacts and contacts of contacts who were absent at the time of the trial team visit. The list was archived, then we randomly assigned clusters (1:1) to either immediate vaccination or delayed vaccination (21 days later) of all eligible individuals (eg, those aged ≥18 years and not pregnant, breastfeeding, or severely ill). An independent statistician generated the assignment sequence using block randomisation with randomly varying blocks, stratified by location (urban vs rural) and size of rings (≤20 individuals vs >20 individuals). Ebola response teams and laboratory workers were unaware of assignments. After a recommendation by an independent data and safety monitoring board, randomisation was stopped and immediate vaccination was also offered to children aged 6-17 years and all identified rings. The prespecified primary outcome was a laboratory confirmed case of Ebola virus disease with onset 10 days or more from randomisation. The primary analysis compared the incidence of Ebola virus disease in eligible and vaccinated individuals assigned to immediate

  4. Occurrence and severity of lung lesions in slaughter pigs vaccinated against Mycoplasma hyopneumoniae with different strategies.

    Science.gov (United States)

    Hillen, Sonja; von Berg, Stephan; Köhler, Kernt; Reinacher, Manfred; Willems, Hermann; Reiner, Gerald

    2014-03-01

    Different vaccination strategies against Mycoplasma hyopneumoniae have been adopted worldwide. Reports from the field indicate varying levels of protection among currently available vaccines. The goal of the present study was to compare the efficacies of three widespread commercial vaccination strategies against M. hyopneumoniae under field conditions. 20 farms were included. 14 farms used different single dose vaccines (vaccine 1 [V1], 8 herds; vaccine 2 [V2], 6 herds); another 6 farms (V3) used a two dose vaccination strategy. Gross lesions of 854 lungs and histopathology from 140 lungs were quantified, and a quantitative PCR was applied to detect M. hyopneumoniae and porcine circovirus 2 (PCV2) DNA in lung tissue (n=140). In addition, porcine reproductive and respiratory disease virus (PRRSV), swine influenza virus (SIV), Actinobacillus pleuropneumoniae, Haemophilus parasuis and Pasteurella multocida were tested by qualitative PCR. 53% of lungs were positive for M. hyopneumoniae. 55.9% of lungs showed macroscopic enzootic pneumonia (EP)-like lesions. Lung lesion scores (Phyopneumoniae-loads (Phyopneumoniae indicating that the applied diagnostic tools are valuable in confirming the prevalence and severity of M. hyopneumoniae infections. Comparing different vaccination strategies against M. hyopneumoniae indicates varying levels of protection. M. hyopneumoniae is still a major problem despite the widely applied vaccination. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Efficacy and safety of a pentavalent live human-bovine reassortant rotavirus vaccine (RV5) in healthy Chinese infants: A randomized, double-blind, placebo-controlled trial.

    Science.gov (United States)

    Mo, Zhaojun; Mo, Yi; Li, Mingqiang; Tao, Junhui; Yang, Xu; Kong, Jilian; Wei, Dingkai; Fu, Botao; Liao, Xueyan; Chu, Jianli; Qiu, Yuanzheng; Hille, Darcy A; Nelson, Micki; Kaplan, Susan S

    2017-10-13

    A randomized, double-blind, placebo-controlled multicenter trial was conducted in healthy Chinese infants to assess the efficacy and safety of a pentavalent live human-bovine reassortant rotavirus vaccine (RotaTeq™, RV5) against rotavirus gastroenteritis (RVGE). 4040 participants aged 6-12weeks were enrolled and randomly assigned to either 3 oral doses of RV5 (n=2020) or placebo (n=2020), administered ∼4weeks apart. The participants also received OPV and DTaP in a concomitant or staggered fashion. The primary objective was to evaluate vaccine efficacy (VE) against naturally-occurring RVGE at least 14days following the third dose. Key secondary objectives included: VE against naturally-occurring severe RVGE and VE against severe and any-severity RVGE caused by rotavirus serotypes contained in the vaccine, occurring at least 14days after the third dose. All adverse events (AEs) were collected for 30days following each dose. Serious AEs (SAEs) and intussusception cases were collected during the entire study. (ClinicalTrials.gov registry: NCT02062385). VE against RVGE of any-severity caused by any serotype was 69.3% (95% CI: 54.5, 79.7). The secondary efficacy analysis showed an efficacy of: 78.9% (95% CI: 59.1, 90.1) against severe RVGE caused by any serotype; 69.9% (95% CI: 55.2, 80.3) and 78.9% (95% CI: 59.1, 90.1) against any-severity and severe RVGE caused by serotypes contained in the vaccine, respectively. Within 30days following any vaccination, 53.5% (1079/2015) and 53.3% (1077/2019) of participants reported at least one AE, and 5.8% (116/2015) and 5.7% (116/2019) reported SAEs in the vaccine and placebo groups, respectively. No SAEs were considered vaccine-related in recipients of RV5. Two intussusception cases were reported in recipients of RV5 who recovered after receiving treatment. Neither was considered vaccine-related. In Chinese infants, RV5 was efficacious against any-severity and severe RVGE caused by any serotype and generally well

  6. Efficacy, safety and effectiveness of licensed rotavirus vaccines: a systematic review and meta-analysis for Latin America and the Caribbean.

    Science.gov (United States)

    Velázquez, Raúl F; Linhares, Alexandre C; Muñoz, Sergio; Seron, Pamela; Lorca, Pedro; DeAntonio, Rodrigo; Ortega-Barria, Eduardo

    2017-01-13

    RotaTeq™ (RV5; Merck & Co. Inc., USA) and Rotarix™ (RV1, GlaxoSmithKline, Belgium) vaccines, developed to prevent rotavirus diarrhea in children under five years old, were both introduced into national immunization programs in 2006. As many countries in Latin America and the Caribbean have included either RV5 or RV1 in their routine childhood vaccination programs, we conducted a systematic review and meta-analysis to analyze efficacy, safety and effectiveness data from the region. We conducted a systematic search in PubMed, EMBASE, Scielo, Lilacs and the Cochrane Central Register, for controlled efficacy, safety and effectiveness studies published between January 2000 until December 2011, on RV5 and RV1 across Latin America (where both vaccines are available since 2006). The primary outcome measures were: rotavirus-related gastroenteritis of any severity; rotavirus emergency department visits and hospitalization; and severe adverse events. The results of the meta-analysis for efficacy show that RV1 reduced the risk of any-severity rotavirus-related gastroenteritis by 65% (relative risk (RR) 0.35, 95% confidence interval (CI) 0.25; 0.50), and of severe gastroenteritis by 82% (RR 0.18, 95%CI 0.12; 0.26) versus placebo. In trials, both vaccines significantly reduced the risk of hospitalization and emergency visits by 85% (RR 0.15, 95%CI 0.09; 0.25) for RV1 and by 90% (RR 0.099, 95%CI 0.012; 0.77) for RV5. Vaccination with RV5 or RV1 did not increase the risk of death, intussusception, or other severe adverse events which were previously associated with the first licensed rotavirus vaccine. Real-world effectiveness studies showed that both vaccines reduced rotavirus hospitalization in the region by around 45-50% for RV5 (for 1 to 3 doses, respectively), and, by around 50-80% for RV1 (for 1 to 2 doses, respectively). For RV1, effectiveness against hospitalization was highest (around 80-96%) for children vaccinated before 12 months of age, compared with 5

  7. Efficacy and safety of simultaneous vaccination with two modified live virus vaccines against porcine reproductive and respiratory syndrome virus types 1 and 2 in pigs

    DEFF Research Database (Denmark)

    Kristensen, Charlotte S.; Kvisgaard, Lise Kirstine; Pawlowski, Maciej

    2018-01-01

    from groups 1–4 were mingled in new groups and challenged (DPC 0) with PRRSV-1, subtype 1, PRRSV-1, subtype 2 or PRRSV-2. On DPC 13/14 all pigs were necropsied. Samples were collected after vaccination and challenge. PRRSV was detected in all vaccinated pigs and the majority of the pigs were positive...... there was limited effect on the viral load in serum following challenge with the PRRSV-1 strains. Vaccination against PRRSV-1 had less impact on viremia following challenge. The protective effects of simultaneous vaccination with PRRSV Type 1 and 2 MLV vaccines and single PRRS MLV vaccination were comparable. None....... Thus, simultaneous administration of the two vaccines is an option in herds with both PRRSV types....

  8. Engineering vaccines against hemorrhagic septicemia in ruminants ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    2018-01-12

    Jan 12, 2018 ... ... disease in cattle and buffaloes; globally the disease ranks second in ... of stimulating protective immune responses against all known variants of the bacteria. ... Accelerating vaccine development for African swine fever virus ...

  9. A study of vaccine-induced immune pressure on breakthrough infections in the Phambili phase 2b HIV-1 vaccine efficacy trial

    Science.gov (United States)

    Rolland, M.; Magaret, C.A.; Rademeyer, C.; Fiore-Gartland, A.; Edlefsen, P.T.; DeCamp, A.; Ahmed, H.; Ngandu, N.; Larsen, B.B.; Frahm, N.; Marais, J.; Thebus, R.; Geraghty, D.; Hural, J.; Corey, L.; Kublin, J.; Gray, G.; McElrath, M.J.; Mullins, J.I.; Gilbert, P.B.; Williamson, C.

    2016-01-01

    Introduction The Merck Adenovirus-5 Gag/Pol/Nef HIV-1 subtype-B vaccine evaluated in predominately subtype B epidemic regions (Step Study), while not preventing infection, exerted vaccine-induced immune pressure on HIV-1 breakthrough infections. Here we investigated if the same vaccine exerted immune pressure when tested in the Phambili Phase 2b study in a subtype C epidemic. Materials and methods A sieve analysis, which compares breakthrough viruses from placebo and vaccine arms, was performed on 277 near full-length genomes generated from 23 vaccine and 20 placebo recipients. Vaccine coverage was estimated by computing the percentage of 9-mers that were exact matches to the vaccine insert. Results There was significantly greater protein distances from the vaccine immunogen sequence in Gag (p = 0.045) and Nef (p = 0.021) in viruses infecting vaccine recipients compared to placebo recipients. Twenty-seven putative sites of vaccine-induced pressure were identified (p sieve effect in Step was driven by HLA A*02:01; an allele which was found in low frequency in Phambili participants compared to Step participants. Furthermore, the coverage of the vaccine against subtype C Phambili viruses was 31%, 46% and 14% for Gag, Pol and Nef, respectively, compared to subtype B Step virus coverage of 56%, 61% and 26%, respectively. Discussion This study presents evidence of sieve effects in Gag and Nef; however could not confirm effects on specific amino acid sites. We propose that this weaker signal of vaccine immune pressure detected in the Phambili study compared to the Step study may have been influenced by differences in host genetics (HLA allele frequency) and reduced impact of vaccine-induced immune responses due to mismatch between the viral subtype in the vaccine and infecting subtypes. PMID:27756485

  10. Protective efficacy of a single immunization with capripoxvirus-vectored recombinant peste des petits ruminants vaccines in presence of pre-existing immunity.

    Science.gov (United States)

    Caufour, Philippe; Rufael, Tesfaye; Lamien, Charles Euloge; Lancelot, Renaud; Kidane, Menbere; Awel, Dino; Sertse, Tefera; Kwiatek, Olivier; Libeau, Geneviève; Sahle, Mesfin; Diallo, Adama; Albina, Emmanuel

    2014-06-24

    Sheeppox, goatpox and peste des petits ruminants (PPR) are highly contagious ruminant diseases widely distributed in Africa, the Middle East and Asia. Capripoxvirus (CPV)-vectored recombinant PPR vaccines (rCPV-PPR vaccines), which have been developed and shown to protect against both Capripox (CP) and PPR, would be critical tools in the control of these important diseases. In most parts of the world, these disease distributions overlap each other leaving concerns about the potential impact that pre-existing immunity against either disease may have on the protective efficacy of these bivalent rCPV-PPR vaccines. Currently, this question has not been indisputably addressed. Therefore, we undertook this study, under experimental conditions designed for the context of mass vaccination campaigns of small ruminants, using the two CPV recombinants (Kenya sheep-1 (KS-1) strain-based constructs) developed previously in our laboratory. Pre-existing immunity was first induced by immunization either with an attenuated CPV vaccine strain (KS-1) or the attenuated PPRV vaccine strain (Nigeria 75/1) and animals were thereafter inoculated once subcutaneously with a mixture of CPV recombinants expressing either the hemagglutinin (H) or the fusion (F) protein gene of PPRV (10(3) TCID50/animal of each). Finally, these animals were challenged with a virulent CPV strain followed by a virulent PPRV strain 3 weeks later. Our study demonstrated full protection against CP for vaccinated animals with prior exposure to PPRV and a partial protection against PPR for vaccinated animals with prior exposure to CPV. The latter animals exhibited a mild clinical form of PPR and did not show any post-challenge anamnestic neutralizing antibody response against PPRV. The implications of these results are discussed herein and suggestions made for future research regarding the development of CPV-vectored vaccines. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Clinical efficacy and safety of a novel tetravalent dengue vaccine in healthy children in Asia: a phase 3, randomised, observer-masked, placebo-controlled trial.

    Science.gov (United States)

    Capeding, Maria Rosario; Tran, Ngoc Huu; Hadinegoro, Sri Rezeki S; Ismail, Hussain Imam H J Muhammad; Chotpitayasunondh, Tawee; Chua, Mary Noreen; Luong, Chan Quang; Rusmil, Kusnandi; Wirawan, Dewa Nyoman; Nallusamy, Revathy; Pitisuttithum, Punnee; Thisyakorn, Usa; Yoon, In-Kyu; van der Vliet, Diane; Langevin, Edith; Laot, Thelma; Hutagalung, Yanee; Frago, Carina; Boaz, Mark; Wartel, T Anh; Tornieporth, Nadia G; Saville, Melanie; Bouckenooghe, Alain

    2014-10-11

    An estimated 100 million people have symptomatic dengue infection every year. This is the first report of a phase 3 vaccine efficacy trial of a candidate dengue vaccine. We aimed to assess the efficacy of the CYD dengue vaccine against symptomatic, virologically confirmed dengue in children. We did an observer-masked, randomised controlled, multicentre, phase 3 trial in five countries in the Asia-Pacific region. Between June 3, and Dec 1, 2011, healthy children aged 2-14 years were randomly assigned (2:1), by computer-generated permuted blocks of six with an interactive voice or web response system, to receive three injections of a recombinant, live, attenuated, tetravalent dengue vaccine (CYD-TDV), or placebo, at months 0, 6, and 12. Randomisation was stratified by age and site. Participants were followed up until month 25. Trial staff responsible for the preparation and administration of injections were unmasked to group allocation, but were not included in the follow-up of the participants; allocation was concealed from the study sponsor, investigators, and parents and guardians. Our primary objective was to assess protective efficacy against symptomatic, virologically confirmed dengue, irrespective of disease severity or serotype, that took place more than 28 days after the third injection. The primary endpoint was for the lower bound of the 95% CI of vaccine efficacy to be greater than 25%. Analysis was by intention to treat and per procotol. This trial is registered with ClinicalTrials.gov, number NCT01373281. We randomly assigned 10,275 children to receive either vaccine (n=6851) or placebo (n=3424), of whom 6710 (98%) and 3350 (98%), respectively, were included in the primary analysis. 250 cases of virologically confirmed dengue took place more than 28 days after the third injection (117 [47%] in the vaccine group and 133 [53%] in the control group). The primary endpoint was achieved with 56·5% (95% CI 43·8-66·4) efficacy. We recorded 647 serious adverse

  12. Specific microtubule-depolymerizing agents augment efficacy of dendritic cell-based cancer vaccines

    Directory of Open Access Journals (Sweden)

    Chang Wei-Ting

    2011-06-01

    Full Text Available Abstract Background Damage-associated molecular patterns (DAMPs are associated with immunogenic cell death and have the ability to enhance maturation and antigen presentation of dendritic cells (DCs. Specific microtubule-depolymerizing agents (MDAs such as colchicine have been shown to confer anti-cancer activity and also trigger activation of DCs. Methods In this study, we evaluated the ability of three MDAs (colchicine and two 2-phenyl-4-quinolone analogues to induce immunogenic cell death in test tumor cells, activate DCs, and augment T-cell proliferation activity. These MDAs were further evaluated for use as an adjuvant in a tumor cell lysate-pulsed DC vaccine. Results The three test phytochemicals considerably increased the expression of DAMPs including HSP70, HSP90 and HMGB1, but had no effect on expression of calreticulin (CRT. DC vaccines pulsed with MDA-treated tumor cell lysates had a significant effect on tumor growth, showed cytotoxic T-lymphocyte activity against tumors, and increased the survival rate of test mice. In vivo antibody depletion experiments suggested that CD8+ and NK cells, but not CD4+ cells, were the main effector cells responsible for the observed anti-tumor activity. In addition, culture of DCs with GM-CSF and IL-4 during the pulsing and stimulation period significantly increased the production of IL-12 and decreased production of IL-10. MDAs also induced phenotypic maturation of DCs and augmented CD4+ and CD8+ T-cell proliferation when co-cultured with DCs. Conclusions Specific MDAs including the clinical drug, colchicine, can induce immunogenic cell death in tumor cells, and DCs pulsed with MDA-treated tumor cell lysates (TCLs can generate potent anti-tumor immunity in mice. This approach may warrant future clinical evaluation as a cancer vaccine.

  13. Efficacy of human papillomavirus l1 protein vaccines (cervarix and gardasil in reducing the risk of cervical intraepithelial neoplasia: A meta-analysis

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Haghshenas

    2017-01-01

    Full Text Available Human papillomavirus (HPV can induce cervical intraepithelial neoplasia (CIN. Vaccination against HPV can play an important role in CIN prevention. This study aims to estimate the efficacy of L1 protein vaccines (Cervarix and Gardasil in CIN 1, 2, 3 risk reduction using meta-analysis. Relevant articles were identified by two independent researchers searching international databanks. After application of inclusion/exclusion criteria and quality assessment, eligible articles were entered into the final meta-analysis. Inverse variance method and fixed effect model were used to combine the results of the primary studies. The heterogeneity between the results was assessed using Cochrane and I2 indices. Of 11,530 evidence identified during the primary search, three papers were found eligible for meta-analysis, including 7213 participants in the intervention groups and 7170 healthy controls. The efficacy (95% confidence interval of HPV 6, 11, 16, 18 monovalent and quadrivalent vaccines against CIN 1, CIN 2, and CIN 3 were estimated as of 95% (88–98, 97% (85–99, and 95% (78–99, respectively. This study showed that L1 protein vaccines Cervarix and Gardasil are highly protective vaccines playing an effective role in the prevention of HPV 6, 11, 16, 18 which are responsible for CIN 1, CIN 2, and CIN 3.

  14. The GMZ2 malaria vaccine: from concept to efficacy in humans

    DEFF Research Database (Denmark)

    Theisen, Michael; Adu, Bright; Mordmueller, Benjamin

    2017-01-01

    Introduction: GMZ2 is a recombinant protein consisting of conserved domains of GLURP and MSP3, two asexual blood-stage antigens of Plasmodium falciparum, and is designed with the aim of mimicking naturally acquired anti-malarial immunity. The rationale for combining these two antigens is based...... to review the progress and future prospects for clinical development of GMZ2 sub-unit vaccine. We will focus on discovery, naturally acquired immunity, functional activity of specific antibodies, sequence diversity, production, pre-clinical and clinical studies. Expert commentary: GMZ2 is well tolerated...

  15. Self-assembling protein nanoparticles with built-in flagellin domains increases protective efficacy of a Plasmodium falciparum based vaccine.

    Science.gov (United States)

    Kaba, Stephen A; Karch, Christopher P; Seth, Labdhi; Ferlez, Karen M B; Storme, Casey K; Pesavento, Danielle M; Laughlin, Paige Y; Bergmann-Leitner, Elke S; Burkhard, Peter; Lanar, David E

    2018-02-01

    To eliminate the problems associated with the use of extraneous adjuvants we have designed a Self-Assembling Protein Nanoparticle (SAPN) containing epitopes from the Plasmodium falciparum circumsporozoite protein (PfCSP) (designated FMP014) and portions of the TLR5 agonist flagellin (designated FMP014 D0D1 ) as an intrinsic adjuvant. By combining different molar ratios of FMP014 to FMP014 D0D1 monomers before self-assembly, we generated multiple nanoparticles and investigated their biophysical characteristics, immunogenicity and protective efficacy. Immunization with the construct formulated with the ratio 58:2 of FMP014 to FMP014 D0D1 had the highest protective efficacy against a challenge with a transgenic P. berghei sporozoite expressing PfCSP. Increasing the proportion of flagellin per particle resulted in an inverse relationship with levels of both antibody titers and protection. The cytokine profiles of the various immunization groups were evaluated and quantitative amounts of the cytokines IL-2, IFN-γ, IL-12/p70 (Th1); IL4, IL5 (Th2); TNF-α, IL1β, IL-6, KC/GRO (pro-inflammatory), and IL-10 (immunomodulatory) were measured. The relationship of the cytokines to each other revealed a strong immunomodulatory effect depending on the proportion of flagellin in the construct. Our results demonstrate that SAPNs with flagellin may be a promising strategy for the development and delivery of a safe vaccine for infectious diseases. Published by Elsevier Ltd.

  16. Final efficacy, immunogenicity, and safety analyses of a nine-valent human papillomavirus vaccine in women aged 16-26 years

    DEFF Research Database (Denmark)

    Huh, Warner K; Joura, Elmar A; Giuliano, Anna R

    2017-01-01

    BACKGROUND: Primary analyses of a study in young women aged 16-26 years showed efficacy of the nine-valent human papillomavirus (9vHPV; HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58) vaccine against infections and disease related to HPV 31, 33, 45, 52, and 58, and non-inferior HPV 6, 11, 16, and 18...... antibody responses when compared with quadrivalent HPV (qHPV; HPV 6, 11, 16, and 18) vaccine. We aimed to report efficacy of the 9vHPV vaccine for up to 6 years following first administration and antibody responses over 5 years. METHODS: We undertook this randomised, double-blind, efficacy, immunogenicity......, and safety study of the 9vHPV vaccine study at 105 study sites in 18 countries. Women aged 16-26 years old who were healthy, with no history of abnormal cervical cytology, no previous abnormal cervical biopsy results, and no more than four lifetime sexual partners were randomly assigned (1:1) by central...

  17. Characterization of three porcine reproductive and respiratory syndrome virus isolates from a single swine farm bearing strong homology to a vaccine strain.

    Science.gov (United States)

    Jiang, Yi-feng; Xia, Tian-qi; Zhou, Yan-jun; Yu, Ling-xue; Yang, Shen; Huang, Qin-feng; Li, Li-wei; Gao, Fei; Qu, Ze-hui; Tong, Wu; Tong, Guang-zhi

    2015-09-30

    Three porcine reproductive and respiratory syndrome viruses (PRRSV), NT1, NT2, and NT3, were isolated from three dying piglets from a single pig farm in Jiangsu Province, China. Whole genome sequencing revealed that the three isolates share the highest homology with JXA1-P80, an attenuated vaccine strain developed by serial passage of highly pathogenic PRRSV JXA1 in MARC-145 cells. More than ten amino acids residues in ORF1a, ORF1b, GP4, and GP5 that were thought to be unique to JXA1 attenuated on MARC-145 cells were each found in the corresponding locations of NT1, NT2, and NT3. In virulence assays, piglets infected with NT1, NT2, or NT3 exhibited clinical signs of disease, including high fever, anorexia, and respiratory distress, leading to the death of the majority of the piglets within two weeks. Collectively, these data indicate that NT1, NT2, and NT3 are highly pathogenic PRRSVs and they are likely to be revertants of the vaccine strain JXA1-P80. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Human rotavirus vaccine (RIX4414) efficacy in the first two years of life: a randomized, placebo-controlled trial in China.

    Science.gov (United States)

    Li, Rong-cheng; Huang, Teng; Li, Yanping; Luo, Dong; Tao, Junhui; Fu, Botao; Si, Guoai; Nong, Yi; Mo, Zhaojun; Liao, XueYan; Luan, Ivy; Tang, Haiwen; Rathi, Niraj; Karkada, Naveen; Han, Htay Htay

    2014-01-01

    Rotaviruses (RV) are a major cause of severe gastroenteritis (GE) in children agedefficacy of two oral doses of the human rotavirus vaccine (RIX4414) in infants during the first two years of life (113808/NCT01171963). Healthy infants aged 6-16 weeks were randomized (1:1) to receive two oral doses of either the RIX4414 vaccine/placebo according to a 0, 1 month schedule. Vaccine efficacy (VE) against severe RVGE was assessed from two weeks post-Dose 2 up until the end of the second RV season and calculated with its 95% confidence intervals (CI). The primary efficacy objective was met if the lower limit of the 95% CI on VE was ≥10%. Unsolicited symptoms reported during the 31-d post-vaccination follow-up period and serious adverse events (SAEs) reported throughout the study were assessed. Of 3333 enrolled infants, 3148 were included in the according-to-protocol efficacy cohort. Over two consecutive RV seasons, fewer severe RVGE episodes were reported in the RIX4414 group (n=21) vs. the placebo group (n=75). VE against severe RVGE was 72% (95% CI: 54.1-83.6); the lower limit of the 95% CI on VE was >10%. The number of unsolicited symptoms and SAEs reported was similar between both groups. Thirteen deaths (RIX4414=6; placebo=7) occurred during the study. All SAEs and deaths in the RIX4414 group were considered unrelated to vaccination. Two oral doses of RIX4414 vaccine provided a substantial level of protection against severe RVGE in Chinese children during the first two years of life.

  19. A Plasmodium Promiscuous T Cell Epitope Delivered within the Ad5 Hexon Protein Enhances the Protective Efficacy of a Protein Based Malaria Vaccine.

    Directory of Open Access Journals (Sweden)

    Jairo Andres Fonseca

    Full Text Available A malaria vaccine is a public health priority. In order to produce an effective vaccine, a multistage approach targeting both the blood and the liver stage infection is desirable. The vaccine candidates also need to induce balanced immune responses including antibodies, CD4+ and CD8+ T cells. Protein-based subunit vaccines like RTS,S are able to induce strong antibody response but poor cellular reactivity. Adenoviral vectors have been effective inducing protective CD8+ T cell responses in several models including malaria; nonetheless this vaccine platform exhibits a limited induction of humoral immune responses. Two approaches have been used to improve the humoral immunogenicity of recombinant adenovirus vectors, the use of heterologous prime-boost regimens with recombinant proteins or the genetic modification of the hypervariable regions (HVR of the capsid protein hexon to express B cell epitopes of interest. In this study, we describe the development of capsid modified Ad5 vectors that express a promiscuous Plasmodium yoelii T helper epitope denominated PyT53 within the hexon HVR2 region. Several regimens were tested in mice to determine the relevance of the hexon modification in enhancing protective immune responses induced by the previously described protein-based multi-stage experimental vaccine PyCMP. A heterologous prime-boost immunization regime that combines a hexon modified vector with transgenic expression of PyCMP followed by protein immunizations resulted in the induction of robust antibody and cellular immune responses in comparison to a similar regimen that includes a vector with unmodified hexon. These differences in immunogenicity translated into a better protective efficacy against both the hepatic and red blood cell stages of P. yoelii. To our knowledge, this is the first time that a hexon modification is used to deliver a promiscuous T cell epitope. Our data support the use of such modification to enhance the immunogenicity

  20. Comparative efficacy and immunogenicity of replication-defective, recombinant glycoprotein, and DNA vaccines for herpes simplex virus 2 infections in mice and guinea pigs.

    Science.gov (United States)

    Hoshino, Yo; Dalai, Sarat K; Wang, Kening; Pesnicak, Lesley; Lau, Tsz Y; Knipe, David M; Cohen, Jeffrey I; Straus, Stephen E

    2005-01-01

    Many candidate vaccines are effective in animal models of genital herpes simplex virus type 2 (HSV-2) infection. Among them, clinical trials showed moderate protection from genital disease with recombinant HSV-2 glycoprotein D (gD2) in alum-monophosphoryl lipid A adjuvant only in HSV women seronegative for both HSV-1 and HSV-2, encouraging development of additional vaccine options. Therefore, we undertook direct comparative studies of the prophylactic and therapeutic efficacies and immunogenicities of three different classes of candidate vaccines given in four regimens to two species of animals: recombinant gD2, a plasmid expressing gD2, and dl5-29, a replication-defective strain of HSV-2 with the essential genes UL5 and UL29 deleted. Both dl5-29 and gD2 were highly effective in attenuating acute and recurrent disease and reducing latent viral load, and both were superior to the plasmid vaccine alone or the plasmid vaccine followed by one dose of dl5-29. dl5-29 was also effective in treating established infections. Moreover, latent dl5-29 virus could not be detected by PCR in sacral ganglia from guinea pigs vaccinated intravaginally. Finally, dl5-29 was superior to gD2 in inducing higher neutralizing antibody titers and the more rapid accumulation of HSV-2-specific CD8+ T cells in trigeminal ganglia after challenge with wild-type virus. Given its efficacy, its defectiveness for latency, and its ability to induce rapid, virus-specific CD8(+)-T-cell responses, the dl5-29 vaccine may be a good candidate for early-phase human trials.

  1. Comparative evaluation of live marker vaccine candidates "CP7_E2alf" and "flc11" along with C-strain "Riems" after oral vaccination

    NARCIS (Netherlands)

    Blome, S.; Aebischer, A.; Lange, E.; Hofmann, M.; Leifer, I.; Loeffen, W.L.A.; Koenen, F.; Beer, M.

    2012-01-01

    Due to the tremendous socio-economic impact of classical swine fever (CSF) outbreaks, emergency vaccination scenarios are continuously under discussion. Unfortunately, all currently available vaccines show restrictions either in terms of marker capacities or immunogenicity. Recent research efforts

  2. Oral vaccination of fish

    NARCIS (Netherlands)

    Embregts, Carmen W.E.; Forlenza, Maria

    2016-01-01

    The limited number of oral vaccines currently approved for use in humans and veterinary species clearly illustrates that development of efficacious and safe oral vaccines has been a challenge not only for fish immunologists. The insufficient efficacy of oral vaccines is partly due to antigen

  3. Immunogenicity and protective efficacy of a single-dose live non-pathogenic Escherichia coli oral vaccine against F4-positive enterotoxigenic Escherichia coli challenge in pigs.

    Science.gov (United States)

    Fairbrother, John Morris; Nadeau, Éric; Bélanger, Louise; Tremblay, Cindy-Love; Tremblay, Danielle; Brunelle, Mélanie; Wolf, Regina; Hellmann, Klaus; Hidalgo, Álvaro

    2017-01-05

    Enterotoxigenic Escherichia coli strains expressing F4 (K88) fimbriae (F4-ETEC) are one of the most important causes of post-weaning diarrhea (PWD) in pigs. F4, a major antigen, plays an important role in the early steps of the infection. Herein, the efficacy of a live oral vaccine consisting of a non-pathogenic E. coli strain expressing F4 for protection of pigs against PWD was evaluated. Three blinded, placebo-controlled, block design, parallel-group confirmatory experiments were conducted, using an F4-ETEC PWD challenge model, each with a different vaccination-challenge interval (3, 7, and 21days). The pigs were vaccinated via the drinking water with a single dose of the Coliprotec® F4 vaccine one day post-weaning. Efficacy was assessed by evaluating diarrhea, clinical observations, intestinal fluid accumulation, weight gain, intestinal colonization and fecal shedding of F4-ETEC. The immune response was evaluated by measuring serum and intestinal F4-specific antibodies. The administration of the vaccine resulted in a significant reduction of the incidence of moderate to severe diarrhea, ileal colonization by F4-ETEC, and fecal shedding of F4-ETEC after the heterologous challenge at 7 and 21days post-vaccination. The 7-day onset of protection was associated with an increase of serum anti-F4 IgM whereas the 21-day duration of protection was associated with an increase of both serum anti-F4 IgM and IgA. Significant correlations between levels of serum and intestinal secretory anti-F4 antibodies were detected. Maternally derived F4-specific serum antibodies did not interfere with the vaccine efficacy. The evaluation of protection following a challenge three days after vaccination showed a reduction of the severity and the duration of diarrhea and of fecal shedding of F4-ETEC. The 7-day onset and the 21-day duration of protection induced by Coliprotec® F4 vaccine administered once in drinking water to pigs of at least 18days of age were confirmed by protection

  4. Efficacy of a Monovalent Human-Bovine (116E) Rotavirus Vaccine in Indian Infants: A Randomised Double Blind Placebo Controlled Trial

    Science.gov (United States)

    Bhandari, Nita; Rongsen-Chandola, Temsunaro; Bavdekar, Ashish; John, Jacob; Antony, Kalpana; Taneja, Sunita; Goyal, Nidhi; Kawade, Anand; Kang, Gagandeep; Rathore, Sudeep Singh; Juvekar, Sanjay; Muliyil, Jayaprakash; Arya, Alok; Shaikh, Hanif; Abraham, Vinod; Vrati, Sudhanshu; Proschan, Michael; Kohberger, Robert; Thiry, Georges; Glass, Roger; Greenberg, Harry B; Curlin, George; Mohan, Krishna; Harshavardhan, GVJA; Prasad, Sai; Rao, TS; Boslego, John; Bhan, Maharaj Kishan

    2015-01-01

    Background Rotavirus is the most common cause of severe dehydrating gastroenteritis in developing countries. Safe, effective, and affordable rotavirus vaccines are needed for developing countries. Methods In a double-blind placebo controlled multicentre trial, 6799 infants aged 6 to 7 weeks were randomised to receive three doses of an oral human-bovine natural reassortant vaccine (116E) or placebo at ages 6, 10, and 14 weeks. Primary outcome was severe (≥11 on the Vesikari scale) rotavirus gastroenteritis. Efficacy outcomes and adverse events were ascertained through active surveillance. Findings At analyses, the median age was 17·2 months; over 96% subjects received all three doses of the vaccine/placebo and ~1% were lost to follow up. 4532 and 2267 subjects were randomly assigned to receive vaccine and placebo, respectively. The per protocol analyses included 4354 subjects in the vaccine and 2187 subjects in the placebo group. 71 events of severe rotavirus gastroenteritis were reported in 4752 person years among the vaccinees compared to 76 events in 2360 person years in the placebo recipients; vaccine efficacy against severe rotavirus gastroenteritis was 53·6% (95% CI 35·0–66·9; Protavirus gastroenteritis episode was 55 (95% CI 37–97). The incidence of severe rotavirus gastroenteritis/100 person years was 1·5 in vaccine and 3·2 in placebo group and an incidence rate ratio of 0·46 (95% CI 0·33–0·65). The absolute rate reduction for severe rotavirus gastroenteritis was 1·7 (95% CI 2·5–0·9). Efficacy against severe gastroenteritis of any aetiology was 18·6% (95% CI 1·9–32·3); it was 24·1% (95% CI 5·8–38·7) in the first year of life. The prevalence of immediate, solicited, and serious adverse events were similar in both groups. There were six cases of intussusception amongst 4532 vaccinees and two amongst 2267 placebo recipients (P=0·73). All intussusception cases occurred after the third dose. Among vaccine and placebo recipients

  5. Improving the Th1 cellular efficacy of the lead Yersinia pestis rF1-V subunit vaccine using SA-4-1BBL as a novel adjuvant.

    Science.gov (United States)

    Dinc, Gunes; Pennington, Jarrod M; Yolcu, Esma S; Lawrenz, Matthew B; Shirwan, Haval

    2014-09-03

    The lead candidate plague subunit vaccine is the recombinant fusion protein rF1-V adjuvanted with alum. While alum generates Th2 regulated robust humoral responses, immune protection against Yersinia pestis has been shown to also involve Th1 driven cellular responses. Therefore, the rF1-V-based subunit vaccine may benefit from an adjuvant system that generates a mixed Th1 and humoral immune response. We herein assessed the efficacy of a novel SA-4-1BBL costimulatory molecule as a Th1 adjuvant to improve cellular responses generated by the rF1-V vaccine. SA-4-1BBL as a single adjuvant had better efficacy than alum in generating CD4(+) and CD8(+) T cells producing TNFα and IFNγ, signature cytokines for Th1 responses. The combination of SA-4-1BBL with alum further increased this Th1 response as compared with the individual adjuvants. Analysis of the humoral response revealed that SA-4-1BBL as a single adjuvant did not generate a significant Ab response against rF1-V, and SA-4-1BBL in combination with alum did not improve Ab titers. However, the combined adjuvants significantly increased the ratio of Th1 regulated IgG2c in C57BL/6 mice to the Th2 regulated IgG1. Finally, a single vaccination with rF1-V adjuvanted with SA-4-1BBL+alum had better protective efficacy than vaccines containing individual adjuvants. Taken together, these results demonstrate that SA-4-1BBL improves the protective efficacy of the alum adjuvanted lead rF1-V subunit vaccine by generating a more balanced Th1 cellular and humoral immune response. As such, this adjuvant platform may prove efficacious not only for the rF1-V vaccine but also against other infections that require both cellular and humoral immune responses for protection. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. Safety, immunogenicity, and efficacy of quadrivalent human papillomavirus (types 6, 11, 16, 18) recombinant vaccine in women aged 24-45 years: a randomised, double-blind trial.

    Science.gov (United States)

    Muñoz, Nubia; Manalastas, Ricardo; Pitisuttithum, Punee; Tresukosol, Damrong; Monsonego, Joseph; Ault, Kevin; Clavel, Christine; Luna, Joaquin; Myers, Evan; Hood, Sara; Bautista, Oliver; Bryan, Janine; Taddeo, Frank J; Esser, Mark T; Vuocolo, Scott; Haupt, Richard M; Barr, Eliav; Saah, Alfred

    2009-06-06

    Although the peak incidence of human papillomavirus (HPV) infection occurs in most populations within 5-10 years of first sexual experience, all women remain at risk for acquisition of HPV infections. We tested the safety, immunogenicity, and efficacy of the quadrivalent HPV (types 6, 11, 16, 18) L1 virus-like-particle vaccine in women aged 24-45 years. Women aged 24-45 years with no history of genital warts or cervical disease were enrolled from community health centres, academic health centres, and primary health-care providers into an ongoing multicentre, parallel, randomised, placebo-controlled, double-blind study. Participants were allocated by computer-generated schedule to receive quadrivalent HPV vaccine (n=1911) or placebo (n=1908) at day 1, and months 2 and 6. All study site investigators and personnel, study participants, monitors, and central laboratory personnel were blinded to treatment allocation. Coprimary efficacy endpoints were 6 months' or more duration of infection and cervical and external genital disease due to HPV 6, 11, 16, 18; and due to HPV 16 and 18 alone. Primary efficacy analyses were done in a per-protocol population, but intention-to-treat analyses were also undertaken. This study is registered with ClinicalTrials.gov, number NCT00090220. 1910 women received at least one dose of vaccine and 1907 at least one dose of placebo. In the per-protocol population, efficacy against the first coprimary endpoint (disease or infection related to HPV 6, 11, 16, and 18) was 90.5% (95% CI 73.7-97.5, four of 1615 cases in the vaccine group vs 41/1607 in the placebo group) and 83.1% (50.6-95.8, four of 1601 cases vs 23/1579 cases) against the second coprimary endpoint (disease or infection related to HPV 16 and 18 alone). In the intention-to-treat population, efficacy against the first coprimary endpoint was 30.9% (95% CI 11.1-46.5, 108/1886 cases vs 154/1883 cases) and against the second coprimary endpoint was 22.6% (-2.9 to 41.9, 90/1886 cases vs

  7. Efficacy of pentavalent rotavirus vaccine against severe rotavirus gastroenteritis in infants in developing countries in sub-Saharan Africa: a randomised, double-blind, placebo-controlled trial.

    Science.gov (United States)

    Armah, George E; Sow, Samba O; Breiman, Robert F; Dallas, Michael J; Tapia, Milagritos D; Feikin, Daniel R; Binka, Fred N; Steele, A Duncan; Laserson, Kayla F; Ansah, Nana A; Levine, Myron M; Lewis, Kristen; Coia, Michele L; Attah-Poku, Margaret; Ojwando, Joel; Rivers, Stephen B; Victor, John C; Nyambane, Geoffrey; Hodgson, Abraham; Schödel, Florian; Ciarlet, Max; Neuzil, Kathleen M

    2010-08-21

    Rotavirus gastroenteritis causes many deaths in infants in sub-Saharan Africa. Because rotavirus vaccines have proven effective in developed countries but had not been tested in developing countries, we assessed efficacy of a pentavalent rotavirus vaccine against severe disease in Ghana, Kenya, and Mali between April, 2007, and March, 2009. In our multicentre, double-blind, placebo-controlled trial, undertaken in rural areas of Ghana and Kenya and an urban area of Mali, we randomly assigned infants aged 4-12 weeks without symptoms of gastrointestinal disorders in a 1:1 ratio to receive three oral doses of pentavalent rotavirus vaccine 2 mL or placebo at around 6 weeks, 10 weeks, and 14 weeks of age. Infants with HIV infection were not excluded. Randomisation was done by computer-generated randomisation sequence in blocks of six. We obtained data for gastrointestinal symptoms from parents on presentation to health-care facilities and clinical data were obtained prospectively by clinicians. The primary endpoint was severe rotavirus gastroenteritis (Vesikari score >or=11), detected by enzyme immunoassay, arising 14 days or more after the third dose of placebo or vaccine to end of study (March 31, 2009; around 21 months of age). Analysis was per protocol; infants who received scheduled doses of vaccine or placebo without intervening laboratory-confirmed naturally occurring rotavirus disease earlier than 14 days after the third dose and had complete clinical and laboratory results were included in the analysis. This study is registered with ClinicalTrials.gov, number NCT00362648. 5468 infants were randomly assigned to receive pentavalent rotavirus vaccine (n=2733) or placebo (n=2735). 2357 infants assigned to vaccine and 2348 assigned to placebo were included in the per-protocol analysis. 79 cases of severe rotavirus gastroenteritis were reported in 2610.6 person-years in the vaccine group, compared with 129 cases in 2585.9 person-years in the placebo group, resulting

  8. Inability to induce consistent T-cell responses recognizing conserved regions within HIIV-1 antigens: a potential mechanism for lack of vaccine efficacy in the step study

    Energy Technology Data Exchange (ETDEWEB)

    Korber, Bette [Los Alamos National Laboratory; Szinger, James [Los Alamos National Laboratory

    2009-01-01

    T cell based vaccines are based upon the induction of CD8+ T cell memory responses that would be effective in inhibiting infection and subsequent replication of an infecting HIV-1 strain, a process that requires a high probability of matching the epitope induced by vaccination with the infecting viral strain. We compared the frequency and specificity of the CTL epitopes elicited by the replication defective AdS gag/pol/nef vaccine used in the STEP trial with the likelihood of encountering those epitopes among recently sequenced Clade B isolates of HIV-1. On average vaccination elicited only one epitope per gene. Importantly, the highly conserved epitopes in gag, pol, and nef (> 80% of strains in the current collection of the Los Alamos database [www.hiv.lanl.gov]) were rarely elicited by vaccination. Moreover there was a statistically significant skewing of the T cell response to relative variable epitopes of each gene; only 20% of persons possessed > 3 T cell responses to epitopes likely to be found in circulating strains in the CladeB populations in which the Step trial was conducted. This inability to elicit T cell responses likely to be found in circulating viral strains is a likely factor in the lack of efficacy of the vaccine utilized in the STEP trial. Modeling of the epitope specific responses elicited by vaccination, we project that a median of 8-10 CD8+ T cell epitopes are required to provide >80% likelihood of eliciting at least 3 CD8+ T cell epitopes that would be found on a circulating population of viruses. Development of vaccine regimens which elicit either a greater breadth of responses or elicit responses to conserved regions of the HIV-1 genome are needed to fully evaluate the concept of whether induction of T cell immunity can alter HIV-1 in vivo.

  9. Modeling the impact of climate and landscape on the efficacy of white tailed deer vaccination for cattle tick control in northeastern Mexico.

    Directory of Open Access Journals (Sweden)

    Agustín Estrada-Peña

    Full Text Available Cattle ticks are distributed worldwide and affect animal health and livestock production. White tailed deer (WTD sustain and spread cattle tick populations. The aim of this study was to model the efficacy of anti-tick vaccination of WTD to control tick infestations in the absence of cattle vaccination in a territory where both host species coexist and sustain cattle tick populations. Agent-based models that included land cover/landscape properties (patch size, distances to patches and climatic conditions were built in a GIS environment to simulate WTD vaccine effectiveness under conditions where unvaccinated cattle shared the landscape. Published and validated information on tick life cycle was used to build models describing tick mortality and developmental rates. Data from simulations were applied to a large territory in northeastern Mexico where cattle ticks are endemic and WTD and cattle share substantial portions of the habitat. WTD movements were simulated together with tick population dynamics considering the actual landscape and climatic features. The size of the vegetation patches and the distance between patches were critical for the successful control of tick infestations after WTD vaccination. The presence of well-connected, large vegetation patches proved essential for tick control, since the tick could persist in areas of highly fragmented habitat. The continued application of one yearly vaccination on days 1-70 for three years reduced tick abundance/animal/patch by a factor of 40 and 60 for R. annulatus and R. microplus, respectively when compared to non-vaccinated controls. The study showed that vaccination of WTD alone during three consecutive years could result in the reduction of cattle tick populations in northeastern Mexico. Furthermore, the results of the simulations suggested the possibility of using vaccines to prevent the spread and thus the re-introduction of cattle ticks into tick-free areas.

  10. A comparison of the oral application and injection routes using the Onderstepoort Biological Products Fowl Typhoid vaccine, its safety, efficacy and duration of protection in commercial laying hens : article

    Directory of Open Access Journals (Sweden)

    C. Purchase

    2008-05-01

    Full Text Available This study was undertaken to establish whether the Onderstepoort Biological Products Fowl Typhoid (OBPft vaccine registered as an injectable vaccine was effective and safe when administered orally to commercial layers. Its efficacy and duration of protection were compared with application by intramuscular injection. Commercial brown layer hens were used as they were found to be highly susceptible to Salmonella gallinarum infections. In the vaccine safety trial birds were euthanased at timed intervals spanning 4 weeks post-vaccination. Necropsies were performed and samples were taken and tested. No clinical signs or mortalities could be attributed to the OBPft vaccine nor could active shedding of the vaccine strain be detected. Slight pathological changes were noted with both routes of vaccination; however, these changes were transient, returning to normal within the observation period. The injected groups showed a better serological response with the rapid serum plate agglutination (RSPA test than the orally vaccinated groups. In the duration of protection trial, birds were challenged at 3-8-week intervals post-vaccination. All unvaccinated birds died. Protection 8 and 16 weeks after vaccination was above 60 %, by 24 weeks after challenge, the vaccine protection was below 30 %. It was found that there was no significant difference (P < 0.05 in the protection offered by either the oral or injected route of vaccination with the OBPft vaccine.

  11. Safety and efficacy of a new octavalent combined Erysipelas, Parvo and Leptospira vaccine in gilts against Leptospira interrogans serovar Pomona associated disease and foetal death.

    Science.gov (United States)

    Jacobs, A A C; Harks, F; Hoeijmakers, M; Collell, M; Segers, R P A M

    2015-07-31

    The safety and protective efficacy of a new octavalent combination vaccine containing inactivated Erysipelothrix rhusiopathiae, Parvovirus, and Leptospira interrogans (sensu lato) serogroups Canicola, Icterohaemorrhagiae, Australis (Bratislava), Grippotyphosa, Pomona and Tarassovi - Porcilis(®) Ery+Parvo+Lepto - was evaluated in laboratory studies and under field conditions. The safety (2× overdose and repeated dose) was tested in 26 gilts. In this study, neither vaccine related temperature increase nor other systemic reactions were observed after intramuscular vaccination. No local reactions were observed except for one animal that had a small local reaction (2cm diameter) that lasted for 5 days after the third vaccination. Efficacy was tested in 40 gilts. A group of 20 gilts was vaccinated at 20 and 24 weeks of age with Porcilis(®) Ery+Parvo+Lepto and a group of 20 age- and source-matched animals served as the control group. The gilts were inseminated at 41 weeks or 66 weeks of age and were challenged with serovar Pomona 10 weeks after insemination, corresponding to 6 months (n=2×10) and 12 months (n=2×10) after the last vaccination. After both the 6- and 12-month challenges the control animals developed clinical signs (fever, lethargy and anorexia) and leptospiraemia as determined by positive blood culture. In addition, both the 6- and 12-month challenges resulted in death of 21% and 27% of the total number of foetuses in the control groups, respectively. Clinical signs and leptospiraemia were statistically significantly lower in vaccinated gilts after both the 6- and 12-month challenges. In addition, foetal death was statistically significantly lower (3% and 2%, respectively) in vaccinated gilts after both the 6- and 12 month challenges. The vaccine was tested further under field conditions on a Portuguese farm with a history of an increasing abortion rate associated with a Leptospira serovar Pomona infection (confirmed by PCR and serology). This study was

  12. Silencing of Foxp3 enhances the antitumor efficacy of GM-CSF genetically modified tumor cell vaccine against B16 melanoma

    Directory of Open Access Journals (Sweden)

    Miguel A

    2017-01-01

    Full Text Available Antonio Miguel,1 Luis Sendra,1 Verónica Noé,2 Carles J Ciudad,2 Francisco Dasí,3,4 David Hervas,5 María José Herrero,1,6 Salvador F Aliño17 1Department of Pharmacology, Faculty of Medicine, University of Valencia, 2Department of Biochemistry and Molecular Biology, Faculty of Pharmacy, University of Barcelona, 3Research University Hospital of Valencia, INCLIVA Health Research Institute, 4Department of Physiology, Faculty of Medicine, University of Valencia Foundation, 5Biostatistics Unit, 6Pharmacogenetics Unit, Instituto de Investigación Sanitaria La Fe (IIS La Fe, 7Clinical Pharmacology Unit, ACM Hospital Universitario y Politécnico La Fe, Valencia, Spain Abstract: The antitumor response after therapeutic vaccination has a limited effect and seems to be related to the presence of T regulatory cells (Treg, which express the immunoregulatory molecules CTLA4 and Foxp3. The blockage of CTLA4 using antibodies has shown an effective antitumor response conducing to the approval of the human anti-CTLA4 antibody ipilimumab by the US Food and Drug Administration. On the other hand, Foxp3 is crucial for Treg development. For this reason, it is an attractive target for cancer treatment. This study aims to evaluate whether combining therapeutic vaccination with CTLA4 or Foxp3 gene silencing enhances the antitumor response. First, the “in vitro” cell entrance and gene silencing efficacy of two tools, 2'-O-methyl phosphorotioate-modified oligonucleotides (2'-OMe-PS-ASOs and polypurine reverse Hoogsteen hairpins (PPRHs, were evaluated in EL4 cells and cultured primary lymphocytes. Following B16 tumor transplant, C57BL6 mice were vaccinated with irradiated B16 tumor cells engineered to produce granulocyte-macrophage colony-stimulating factor (GM-CSF and were intraperitoneally treated with CTLA4 and Foxp3 2'-OMe-PS-ASO before and after vaccination. Tumor growth, mice survival, and CTLA4 and Foxp3 expression in blood cells were measured. The following

  13. Estimating the Efficacy of a Commercial Phase I Inactivated Vaccine in Decreasing the Prevalence of Coxiella burnetii Infection and Shedding in Red Deer (Cervus elaphus

    Directory of Open Access Journals (Sweden)

    David González-Barrio

    2017-12-01

    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

  14. Efficacy of novel lipid-formulated whole bacterial cell vaccines against Mycobacterium avium subsp paratuberculosis in sheep

    NARCIS (Netherlands)

    Griffin, J.F.T.; Hughes, A.D.; Liggett, S.; Farquhar, P.A.; Mackintosh, C.G.; Bakker, D.

    2009-01-01

    Mycobacterium avium subsp. paratuberculosis [MAP], the Causative agent of enteric Johne's disease, incurs significant economic losses to the livestock industry. Prophylactic vaccination can be employed as a control means, however mineral oil-based vaccines Currently in practice have limited

  15. Efficacy of severe acute respiratory syndrome vaccine based on a nonhuman primate adenovirus in the presence of immunity against human adenovirus.

    Science.gov (United States)

    Zhi, Yan; Figueredo, Joanita; Kobinger, Gary P; Hagan, Heather; Calcedo, Roberto; Miller, James R; Gao, Guangping; Wilson, James M

    2006-05-01

    Replication-deficient human adenovirus type 5 (AdH5) vectors can induce strong transgene product-specific cellular and humoral responses. However, many adult humans have neutralizing antibodies (NAbs) against AdH5 as a result of natural infection with this virus. Therefore, a chimpanzee adenovirus C7 (AdC7) vector was developed to circumvent interference by preexisting immunity to AdH5. This study evaluated the impact of preexisting immunity to human adenovirus on the efficacy of adenovirus-based vaccines against the coronavirus that causes severe acute respiratory syndrome (SARS-CoV). Efficacy was assessed after intramuscular injection of the vector into mice and was measured as the frequency of SARS-CoV-specific T cells and NAbs against SARS-CoV. Immunogenicity of the AdH5-based vaccine was significantly attenuated or completely abolished when the preexisting anti-AdH5 NAb titer was higher than 40. Because 27% of human serum samples from the United States tested so far have an anti-AdH5 NAb titer higher than 40, our results suggested that a significant percentage of humans with preexisting anti-AdH5 immunity would not be candidates for vaccination with an AdH5-based genetic vaccine. In contrast, preexisting anti-AdH5 NAbs have a minimal effect on the potency of the AdC7-based genetic vaccine. Taken together, our studies warrant the further development of AdC7 as a vaccine carrier for human trials.

  16. Comparative Safety and Efficacy Profile of a Novel Oil in Water Vaccine Adjuvant Comprising Vitamins A and E and a Catechin in Protective Anti-Influenza Immunity

    Directory of Open Access Journals (Sweden)

    Sapna Patel

    2017-05-01

    Full Text Available Non-replicating vaccines, such as those based on recombinant proteins, require adjuvants and delivery systems, which have thus far depended on mimicking pathogen danger signals and strong pro-inflammatory responses. In search of a safer and more efficacious alternative, we tested whether vaccinations with influenza recombinant hemagglutinin (HA mixed with a novel vegetable oil in water emulsion adjuvant (Natural Immune-enhancing Delivery System, NIDS, based on the immune-enhancing synergy of vitamins A and E and a catechin, could protect against intra-nasal challenge with live influenza virus. Vaccinations of inbred Brag Albino strain c (BALB/c mice, with HA mixed with NIDS compared to other adjuvants, i.e., a squalene oil in water emulsion (Sq. oil, and the Toll Like Receptor 3 (TLR3 agonist Poly (I:C, induced significantly lower select innate pro-inflammatory responses in serum, but induced significantly higher adaptive antibody and splenic T Helper 1 (TH1 or TH2, but not TH17, responses. Vaccinations with NIDS protected against infection, as measured by clinical scores, lung viral loads, and serum hemagglutination inhibition titers. The NIDS exhibited a strong dose sparing effect and the adjuvant action of NIDS was intact in the outbred CD1 mice. Importantly, vaccinations with the Sq. oil, but not NIDS, induced a significantly higher Serum Amyloid P component, an acute phase reactant secreted by hepatocytes, and total serum IgE. Thus, the NIDS may be used as a clinically safer and more efficacious vaccine adjuvant against influenza, and potentially other infectious diseases.

  17. Inactivated Enterovirus 71 Vaccine Produced by 200-L Scale Serum-Free Microcarrier Bioreactor System Provides Cross-Protective Efficacy in Human SCARB2 Transgenic Mouse.

    Science.gov (United States)

    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

    2015-01-01

    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.

  18. Safety, immunogencity, and efficacy of a cold-adapted A/Ann Arbor/6/60 (H2N2) vaccine in mice and ferrets

    International Nuclear Information System (INIS)

    Chen, Grace L.; Lamirande, Elaine W.; Jin Hong; Kemble, George; Subbarao, Kanta

    2010-01-01

    We studied the attenuation, immunogenicity and efficacy of the cold-adapted A/Ann Arbor/6/60 (AA ca) (H2N2) virus in mice and ferrets to evaluate its use in the event of an H2 influenza pandemic. The AA ca virus was restricted in replication in the respiratory tract of mice and ferrets. In mice, 2 doses of vaccine elicited a > 4-fold rise in hemagglutination-inhibition (HAI) titer and resulted in complete inhibition of viral replication following lethal homologous wild-type virus challenge. In ferrets, a single dose of the vaccine elicited a > 4-fold rise in HAI titer and conferred complete protection against homologous wild-type virus challenge in the upper respiratory tract. In both mice and ferrets, the AA ca virus provided significant protection from challenge with heterologous H2 virus challenge in the respiratory tract. The AA ca vaccine is safe, immunogenic, and efficacious against homologous and heterologous challenge in mice and ferrets, supporting the evaluation of this vaccine in clinical trials.

  19. Efficacy, immunogenicity, and safety of two doses of a tetravalent rotavirus vaccine RRV-TV in Ghana with the first dose administered during the neonatal period.

    Science.gov (United States)

    Armah, George E; Kapikian, Albert Z; Vesikari, Timo; Cunliffe, Nigel; Jacobson, Robert M; Burlington, D Bruce; Ruiz, Leonard P

    2013-08-01

    Oral rhesus/rhesus-human reassortant rotavirus tetravalent vaccine (RRV-TV) was licensed in 1998 but withdrawn in 1999 due to a rare association with intussusception, which occurred disproportionately in infants receiving their first dose at ≥90 days of age. This study examined RRV-TV for the prevention of rotavirus gastroenteritis (RV-GE) in Ghana, West Africa, with infants receiving the first dose during the neonatal period and the second before 60 days of age. In a double-blinded, randomized, placebo-controlled trial in Navrongo, Ghana, we recruited neonates to receive 2 doses of RRV-TV or placebo and followed them to age 12 months. In the intention-to-treat population of 998 infants, we measured a vaccine efficacy of 63.1% against RV-GE of any severity associated with any of the 4 serotypes represented in the vaccine and 60.7% against RV-GE associated with any rotavirus serotype. RRV-TV in a 2-dose schedule with the first dose during the neonatal period is efficacious in preventing RV-GE in rural Ghana. Neonatal dosing results in early protection and may be the optimum schedule to avoid or significantly reduce intussusception, now reported to be associated in international settings with the 2 most widely marketed, licensed, live virus, oral rotavirus vaccines.

  20. Efficacy of RTS,S/AS01E malaria vaccine and exploratory analysis on anti-circumsporozoite antibody titres and protection in children aged 5-17 months in Kenya and Tanzania: a randomised controlled trial

    DEFF Research Database (Denmark)

    Olotu, Ally; Lusingu, John; Leach, Amanda

    2011-01-01

    RTS,S/AS01E is the lead candidate malaria vaccine. We recently showed efficacy against clinical falciparum malaria in 5-17 month old children, during an average of 8 months follow-up. We aimed to assess the efficacy of RTS,S/AS01E during 15 months of follow-up.......RTS,S/AS01E is the lead candidate malaria vaccine. We recently showed efficacy against clinical falciparum malaria in 5-17 month old children, during an average of 8 months follow-up. We aimed to assess the efficacy of RTS,S/AS01E during 15 months of follow-up....

  1. Efficacy of a monovalent human-bovine (116E) rotavirus vaccine in Indian infants: a randomised, double-blind, placebo-controlled trial.

    Science.gov (United States)

    Bhandari, Nita; Rongsen-Chandola, Temsunaro; Bavdekar, Ashish; John, Jacob; Antony, Kalpana; Taneja, Sunita; Goyal, Nidhi; Kawade, Anand; Kang, Gagandeep; Rathore, Sudeep Singh; Juvekar, Sanjay; Muliyil, Jayaprakash; Arya, Alok; Shaikh, Hanif; Abraham, Vinod; Vrati, Sudhanshu; Proschan, Michael; Kohberger, Robert; Thiry, Georges; Glass, Roger; Greenberg, Harry B; Curlin, George; Mohan, Krishna; Harshavardhan, G V J A; Prasad, Sai; Rao, T S; Boslego, John; Bhan, Maharaj Kishan

    2014-06-21

    Rotavirus is the most common cause of severe dehydrating gastroenteritis in developing countries. Safe, effective, and affordable rotavirus vaccines are needed in these countries. We aimed to assess the efficacy and tolerability of a monovalent human-bovine rotavirus vaccine for severe rotavirus gastroenteritis in low-resource urban and rural settings in India. We did a randomised double-blind, placebo-controlled, multicentre trial at three sites in Delhi (urban), Pune (rural), and Vellore (urban and rural) between March 11, 2011, and Nov 5, 2012. Infants aged 6-7 weeks were randomly assigned (2:1), via a central interactive voice or web response system with a block size of 12, to receive either three doses of oral human-bovine natural reassortant vaccine (116E) or placebo at ages 6-7 weeks, 10 weeks, and 14 weeks. Infants' families, study investigators, paediatricians in referral hospitals, laboratory staff, and committee members were all masked to treatment allocation. The primary outcome was incidence of severe rotavirus gastroenteritis (≥11 on the Vesikari scale). Efficacy outcomes and adverse events were ascertained through active surveillance. Analysis was by intention to treat and per protocol. The trial is registered with Clinical Trial Registry-India (CTRI/2010/091/000102) and ClinicalTrials.gov (NCT01305109). 4532 infants were assigned to receive the 116E vaccine and 2267 to receive placebo, of whom 4354 (96%) and 2187 (96%) infants, respectively, were included in the primary per-protocol efficacy analysis. 71 events of severe rotavirus gastroenteritis were reported in 4752 person-years in infants in the vaccine group compared with 76 events in 2360 person-years in those in the placebo group; vaccine efficacy against severe rotavirus gastroenteritis was 53·6% (95% CI 35·0-66·9; p=0·0013) and 56·4% (36·6-70·1; protavirus gastroenteritis episode was 55 (95% CI 37-97). The incidence of severe rotavirus gastroenteritis per 100 person-years was 1·5

  2. miR-125b-1 and miR-378a are predictive biomarkers for the efficacy of vaccine treatment against colorectal cancer.

    Science.gov (United States)

    Tanaka, Hironori; Hazama, Shoichi; Iida, Michihisa; Tsunedomi, Ryouichi; Takenouchi, Hiroko; Nakajima, Masao; Tokumitsu, Yukio; Kanekiyo, Shinsuke; Shindo, Yoshitaro; Tomochika, Shinobu; Tokuhisa, Yoshihiro; Sakamoto, Kazuhiko; Suzuki, Nobuaki; Takeda, Shigeru; Yamamoto, Shigeru; Yoshino, Shigefumi; Ueno, Tomio; Hamamoto, Yoshihiko; Fujita, Yusuke; Tanaka, Hiroaki; Tahara, Ko; Shimizu, Ryoichi; Okuno, Kiyotaka; Fujita, Koji; Kuroda, Masahiko; Nakamura, Yusuke; Nagano, Hiroaki

    2017-11-01

    Many clinical trials of peptide vaccines have been conducted. However, these vaccines have provided clinical benefits in only a small fraction of patients. The purpose of the present study was to explore microRNAs (miRNAs) as novel predictive biomarkers for the efficacy of vaccine treatment against colorectal cancer. First, we carried out microarray analysis of pretreatment cancer tissues in a phase I study, in which peptide vaccines alone were given. Candidate miRNAs were selected by comparison of the better prognosis group with the poorer prognosis group. Next, we conducted microarray analysis of cancer tissues in a phase II study, in which peptide vaccines combined with chemotherapy were given. Candidate miRNAs were further selected by a similar comparison of prognosis. Subsequently, we carried out reverse-transcription PCR analysis of phase II cases, separating cancer tissues into cancer cells and stromal tissue using laser capture microdissection. Treatment effect in relation to overall survival (OS) and miRNA expression was analyzed. Three miRNA predictors were negatively associated with OS: miR-125b-1 in cancer cells (P = 0.040), and miR-378a in both cancer cells (P = 0.009) and stromal cells (P colorectal cancer. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  3. MDA5 can be exploited as efficacious genetic adjuvant for DNA vaccination against lethal H5N1 influenza virus infection in chickens.

    Directory of Open Access Journals (Sweden)

    Matthias Liniger

    Full Text Available Chickens lack the retinoic acid-inducible gene I (RIG-I and sense avian influenza virus (AIV infections by means of the melanoma differentiation-associated gene 5 product (chMDA5. Plasmid-driven expression of the N-terminal half of chMDA5 containing the caspase activation and recruitment domains [chMDA5(1-483] triggers interferon-β responses in chicken cells. We hypothesized that mimicking virus infection by chMDA5(1-483 expression may enhance vaccine-induced adaptive immunity. In order to test this, the potential genetic adjuvant properties of chMDA5(1-483 were evaluated in vivo in combination with a suboptimal quantity of a plasmid DNA vaccine expressing haemagglutinin (HA of H5N1 AIV. Co-administration of the HA plasmid with plasmid DNA for chMDA5(1-483 expression resulted in approximately 10-fold higher HA-specific antibody responses than injection of the HA plasmid mixed with empty vector DNA as control. Accordingly, compared with HA DNA vaccination alone, the chMDA5(1-483-adjuvanted HA DNA vaccine mediated enhanced protection against a lethal H5N1 challenge infection in chickens, with reduced clinical signs and cloacal virus shedding. These data demonstrate that innate immune activation by expression of signaling domains of RIG-I-like receptors can be exploited to enhance vaccine efficacy.

  4. Safety and preliminary evidence of biologic efficacy of a mammaglobin-a DNA vaccine in patients with stable metastatic breast cancer.

    Science.gov (United States)

    Tiriveedhi, Venkataswarup; Tucker, Natalia; Herndon, John; Li, Lijin; Sturmoski, Mark; Ellis, Matthew; Ma, Cynthia; Naughton, Michael; Lockhart, A Craig; Gao, Feng; Fleming, Timothy; Goedegebuure, Peter; Mohanakumar, Thalachallour; Gillanders, William E

    2014-12-01

    Mammaglobin-A (MAM-A) is overexpressed in 40% to 80% of primary breast cancers. We initiated a phase I clinical trial of a MAM-A DNA vaccine to evaluate its safety and biologic efficacy. Patients with breast cancer with stable metastatic disease were eligible for enrollment. Safety was monitored with clinical and laboratory assessments. The CD8 T-cell response was measured by ELISPOT, flow cytometry, and cytotoxicity assays. Progression-free survival (PFS) was described using the Kaplan-Meier product limit estimator. Fourteen subjects have been treated with the MAM-A DNA vaccine and no significant adverse events have been observed. Eight of 14 subjects were HLA-A2(+), and the CD8 T-cell response to vaccination was studied in detail. Flow cytometry demonstrated a significant increase in the frequency of MAM-A-specific CD8 T cells after vaccination (0.9% ± 0.5% vs. 3.8% ± 1.2%; P cells (41 ± 32 vs. 215 ± 67 spm; P cell responses, and preliminary evidence suggests improved PFS. Additional studies are required to define the potential of the MAM-A DNA vaccine for breast cancer prevention and/or therapy. ©2014 American Association for Cancer Research.

  5. A deletion within glycoprotein L of Marek's disease virus (MDV) field isolates correlates with a decrease in bivalent MDV vaccine efficacy in contact-exposed chickens.

    Science.gov (United States)

    Tavlarides-Hontz, Phaedra; Kumar, Pankaj M; Amortegui, Juliana Rojas; Osterrieder, Nikolaus; Parcells, Mark S

    2009-06-01

    We examined the functional role of a naturally occurring deletion within the glycoprotein L (gL) gene of Marek's disease virus (MDV) field isolates. We previously showed that this mutation incrementally increased the virulence of an MDV in contact-exposed SPF leghorn chickens, when chickens shedding this virus were co-infected with herpesvirus of turkeys (HVT). In our present study, we examined this mutation using two stocks of the very virulent plus (vv+)MDV strain TK, one of which harbored this deletion (TK1a) while the other did not (TK2a). We report that TK1a replicating in vaccinated chickens overcame bivalent (HVT/SB1) vaccine protection in contact-exposed chickens. Treatment groups exposed to vaccinated chickens inoculated with a 1:1 mix of TK1a and TK2a showed decreased bivalent vaccine efficacy, and this decrease correlated with the prevalence of the gL deletion indicative of TK1a. These results were also found using quadruplicate treatment groups and bivalently vaccinated chickens obtained from a commercial hatchery. As this deletion was found in 25 out of 25 recent field isolates from Delaware, Maryland, North Carolina, Pennsylvania, and Virginia, we concluded that there is a strong selection for this mutation, which appears to have evolved in HVT or bivalently vaccinated chickens. This is the first report of a mutation in a vv+MDV field strain for which a putative biological phenotype has been discerned. Moreover, this mutation in gL has apparently been selected in MDV field isolates through Marek's disease vaccination.

  6. Using a Human Challenge Model of Infection to Measure Vaccine Efficacy: A Randomised, Controlled Trial Comparing the Typhoid Vaccines M01ZH09 with Placebo and Ty21a.

    Directory of Open Access Journals (Sweden)

    Thomas C Darton

    2016-08-01

    Full Text Available Typhoid persists as a major cause of global morbidity. While several licensed vaccines to prevent typhoid are available, they are of only moderate efficacy and unsuitable for use in children less than two years of age. Development of new efficacious vaccines is complicated by the human host-restriction of Salmonella enterica serovar Typhi (S. Typhi and lack of clear correlates of protection. In this study, we aimed to evaluate the protective efficacy of a single dose of the oral vaccine candidate, M01ZH09, in susceptible volunteers by direct typhoid challenge.We performed a randomised, double-blind, placebo-controlled trial in healthy adult participants at a single centre in Oxford (UK. Participants were allocated to receive one dose of double-blinded M01ZH09 or placebo or 3-doses of open-label Ty21a. Twenty-eight days after vaccination, participants were challenged with 104CFU S. Typhi Quailes strain. The efficacy of M01ZH09 compared with placebo (primary outcome was assessed as the percentage of participants reaching pre-defined endpoints constituting typhoid diagnosis (fever and/or bacteraemia during the 14 days after challenge. Ninety-nine participants were randomised to receive M01ZH09 (n = 33, placebo (n = 33 or 3-doses of Ty21a (n = 33. After challenge, typhoid was diagnosed in 18/31 (58.1% [95% CI 39.1 to 75.5] M01ZH09, 20/30 (66.7% [47.2 to 87.2] placebo, and 13/30 (43.3% [25.5 to 62.6] Ty21a vaccine recipients. Vaccine efficacy (VE for one dose of M01ZH09 was 13% [95% CI -29 to 41] and 35% [-5 to 60] for 3-doses of Ty21a. Retrospective multivariable analyses demonstrated that pre-existing anti-Vi antibody significantly reduced susceptibility to infection after challenge; a 1 log increase in anti-Vi IgG resulting in a 71% decrease in the hazard ratio of typhoid diagnosis ([95% CI 30 to 88%], p = 0.006 during the 14 day challenge period. Limitations to the study included the requirement to limit the challenge period prior to treatment to

  7. Using a Human Challenge Model of Infection to Measure Vaccine Efficacy: A Randomised, Controlled Trial Comparing the Typhoid Vaccines M01ZH09 with Placebo and Ty21a.

    Science.gov (United States)

    Darton, Thomas C; Jones, Claire; Blohmke, Christoph J; Waddington, Claire S; Zhou, Liqing; Peters, Anna; Haworth, Kathryn; Sie, Rebecca; Green, Christopher A; Jeppesen, Catherine A; Moore, Maria; Thompson, Ben A V; John, Tessa; Kingsley, Robert A; Yu, Ly-Mee; Voysey, Merryn; Hindle, Zoe; Lockhart, Stephen; Sztein, Marcelo B; Dougan, Gordon; Angus, Brian; Levine, Myron M; Pollard, Andrew J

    2016-08-01

    Typhoid persists as a major cause of global morbidity. While several licensed vaccines to prevent typhoid are available, they are of only moderate efficacy and unsuitable for use in children less than two years of age. Development of new efficacious vaccines is complicated by the human host-restriction of Salmonella enterica serovar Typhi (S. Typhi) and lack of clear correlates of protection. In this study, we aimed to evaluate the protective efficacy of a single dose of the oral vaccine candidate, M01ZH09, in susceptible volunteers by direct typhoid challenge. We performed a randomised, double-blind, placebo-controlled trial in healthy adult participants at a single centre in Oxford (UK). Participants were allocated to receive one dose of double-blinded M01ZH09 or placebo or 3-doses of open-label Ty21a. Twenty-eight days after vaccination, participants were challenged with 104CFU S. Typhi Quailes strain. The efficacy of M01ZH09 compared with placebo (primary outcome) was assessed as the percentage of participants reaching pre-defined endpoints constituting typhoid diagnosis (fever and/or bacteraemia) during the 14 days after challenge. Ninety-nine participants were randomised to receive M01ZH09 (n = 33), placebo (n = 33) or 3-doses of Ty21a (n = 33). After challenge, typhoid was diagnosed in 18/31 (58.1% [95% CI 39.1 to 75.5]) M01ZH09, 20/30 (66.7% [47.2 to 87.2]) placebo, and 13/30 (43.3% [25.5 to 62.6]) Ty21a vaccine recipients. Vaccine efficacy (VE) for one dose of M01ZH09 was 13% [95% CI -29 to 41] and 35% [-5 to 60] for 3-doses of Ty21a. Retrospective multivariable analyses demonstrated that pre-existing anti-Vi antibody significantly reduced susceptibility to infection after challenge; a 1 log increase in anti-Vi IgG resulting in a 71% decrease in the hazard ratio of typhoid diagnosis ([95% CI 30 to 88%], p = 0.006) during the 14 day challenge period. Limitations to the study included the requirement to limit the challenge period prior to treatment to 2

  8. Field trial of efficacy of the Leish-tec® vaccine against canine leishmaniasis caused by Leishmania infantum in an endemic area with high transmission rates.

    Directory of Open Access Journals (Sweden)

    Gabriel Grimaldi

    Full Text Available Because domestic dogs are reservoir hosts for visceral leishmaniasis (VL in Brazil, one of the approaches used to reduce human disease incidence is to cull infected dogs. However, the results of controlled intervention trials based on serological screening of dogs and killing of seropositive animals are equivocal. A prophylactic vaccine to protect dogs from being infectious to the sand fly vector could be an effective strategy to provide sustained control. Here, we investigated whether a currently licensed commercial subunit rA2 protein-saponin vaccine (Leish-tec® had an additional effect to dog culling on reducing the canine infectious populations.This prospective study was conducted in an L. infantum highly endemic area of southeast Brazil. At the onset of the intervention, all of the eligible dogs received through subcutaneous route a three-dose vaccine course at 21-day intervals and a booster on month 12. For the purpose of comparison, newly recruited healthy dogs were included as the exposed control group. To ascertain vaccine-induced protection, dogs were screened on clinical and serological criteria every 6 months for a 2-year follow-up period. Antibody-based tests and histopathological examination of post-mortem tissue specimens from euthanized animals were used as a marker of infection. The standardized vaccine regime, apart from being safe, was immunogenic as immunized animals responded with a pronounced production of anti-A2-specific IgG antibodies. It should be noted the mean seroconversion time for infection obtained among immunized exposed dogs (~ 18 months, which was twice as high as that for unvaccinated ones (~ 9 months. After two transmission cycles completed, the cumulative incidence of infection did differ significantly (P = 0.016 between the vaccinated (27% and unvaccinated (42% dogs. However, the expected efficacy for the vaccine in inducing clinical protection was not evident since 43% of vaccine recipients developed

  9. Analysis by rotavirus gene 6 reverse transcriptase-polymerase chain reaction assay of rotavirus-positive gastroenteritis cases observed during the vaccination phase of the Rotavirus Efficacy and Safety Trial (REST)

    Science.gov (United States)

    Matson, David O; Vesikari, Timo; Dennehy, Penelope; Dallas, Michael D; Goveia, Michelle G; Itzler, Robbin F; Ciarlet, Max

    2014-01-01

    During the vaccination phase of the Rotavirus Efficacy and Safety Trial (REST), the period between the administration of dose 1 through 13 days after the administration of dose 3, there were more wild-type rotavirus gastroenteritis (RVGE) cases among vaccine recipients compared with placebo recipients using the protocol-specified microbiological plaque assay in the clinical-efficacy cohort, a subset of subjects where vaccine efficacy against RVGE of any severity was assessed. In this study, a rotavirus genome segment 6-based reverse transcriptase–polymerase chain reaction assay was applied post hoc to clarify the accuracy of type categorization of all these RVGE cases in vaccine recipients during the vaccination phase of REST. The assay characterized 147 (90%) of 163 re-assayed RVGE cases or rotavirus-associated health care contacts as type-determinable: either wild-type or vaccine-type rotavirus strains. In the clinical-efficacy cohort (N = 5673), 19 (18.8%) of 101 samples from RVGE cases contained wild-type rotavirus, 70 (69.3%) vaccine virus, and 12 (11.9%) were indeterminable. In the large-scale cohort (N = 68,038), 10 (34.5%) of 29 samples from RVGE-related health care contacts contained wild-type rotavirus strains, 15 (51.7%) vaccine-type rotavirus strains, and 4 (13.8%) were indeterminable. Of the 33 samples from RVGE cases in placebo recipients, all were confirmed to contain wild-type rotaviruses. Altogether, this post-hoc re-evaluation showed that the majority (75%) of type-determinable RVGE cases or health care contacts that occurred during the vaccination phase of REST in vaccine recipients were associated with vaccine-type rotavirus strains rather than wild-type rotavirus strains. PMID:25424931

  10. Analysis by rotavirus gene 6 reverse transcriptase-polymerase chain reaction assay of rotavirus-positive gastroenteritis cases observed during the vaccination phase of the Rotavirus Efficacy and Safety Trial (REST).

    Science.gov (United States)

    Matson, David O; Vesikari, Timo; Dennehy, Penelope; Dallas, Michael D; Goveia, Michelle G; Itzler, Robbin F; Ciarlet, Max

    2014-01-01

    During the vaccination phase of the Rotavirus Efficacy and Safety Trial (REST), the period between the administration of dose 1 through 13 days after the administration of dose 3, there were more wild-type rotavirus gastroenteritis (RVGE) cases among vaccine recipients compared with placebo recipients using the protocol-specified microbiological plaque assay in the clinical-efficacy cohort, a subset of subjects where vaccine efficacy against RVGE of any severity was assessed. In this study, a rotavirus genome segment 6-based reverse transcriptase-polymerase chain reaction assay was applied post hoc to clarify the accuracy of type categorization of all these RVGE cases in vaccine recipients during the vaccination phase of REST. The assay characterized 147 (90%) of 163 re-assayed RVGE cases or rotavirus-associated health care contacts as type-determinable: either wild-type or vaccine-type rotavirus strains. In the clinical-efficacy cohort (N = 5673), 19 (18.8%) of 101 samples from RVGE cases contained wild-type rotavirus, 70 (69.3%) vaccine virus, and 12 (11.9%) were indeterminable. In the large-scale cohort (N = 68,038), 10 (34.5%) of 29 samples from RVGE-related health care contacts contained wild-type rotavirus strains, 15 (51.7%) vaccine-type rotavirus strains, and 4 (13.8%) were indeterminable. Of the 33 samples from RVGE cases in placebo recipients, all were confirmed to contain wild-type rotaviruses. Altogether, this post-hoc re-evaluation showed that the majority (75%) of type-determinable RVGE cases or health care contacts that occurred during the vaccination phase of REST in vaccine recipients were associated with vaccine-type rotavirus strains rather than wild-type rotavirus strains.

  11. 9 CFR 85.10 - Interstate movement of swine semen and swine embryos for insemination of or implantation into swine.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Interstate movement of swine semen and... ANIMALS (INCLUDING POULTRY) AND ANIMAL PRODUCTS PSEUDORABIES § 85.10 Interstate movement of swine semen and swine embryos for insemination of or implantation into swine. Swine semen and swine embryos moved...

  12. Safety, efficacy, and immunogenicity of an inactivated influenza vaccine in healthy adults: a randomized, placebo-controlled trial over two influenza seasons

    Directory of Open Access Journals (Sweden)

    Bouveret Nancy

    2010-03-01

    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

  13. The efficacy of a multivalent calicivirus, herpesvirus and parvovirus vaccine and a rabies vaccine is not affected when administered in combination

    Directory of Open Access Journals (Sweden)

    Stephen Wilson

    2015-01-01

    In conclusion, the data show that combining these two separate vaccines in one administration has limited impact on their ability to generate serological responses, and that these responses are still of a magnitude previously demonstrated to be protective.

  14. Immunogenicity and protective efficacy of Semliki forest virus replicon-based DNA vaccines encoding goatpox virus structural proteins

    International Nuclear Information System (INIS)

    Zheng Min; Jin Ningyi; Liu Qi; Huo Xiaowei; Li Yang; Hu Bo; Ma Haili; Zhu Zhanbo; Cong Yanzhao; Li Xiao; Jin Minglan; Zhu Guangze

    2009-01-01

    Goatpox, caused by goatpox virus (GTPV), is an acute feverish and contagious disease in goats often associated with high morbidity and high mortality. To resolve potential safety risks and vaccination side effects of existing live attenuated goatpox vaccine (AV41), two Semliki forest virus (SFV) replicon-based bicistronic expression DNA vaccines (pCSm-AAL and pCSm-BAA) which encode GTPV structural proteins corresponding to the Vaccinia virus proteins A27, L1, A33, and B5, respectively, were constructed. Then, theirs ability to induce humoral and cellular response in mice and goats, and protect goats against virulent virus challenge were evaluated. The results showed that, vaccination with pCSm-AAL and pCSm-BAA in combination could elicit strong humoral and cellular responses in mice and goats, provide partial protection against viral challenge in goats, and reduce disease symptoms. Additionally, priming vaccination with the above-mentioned DNA vaccines could significantly reduce the goats' side reactions from boosting vaccinations with current live vaccine (AV41), which include skin lesions at the inoculation site and fevers. Data obtained in this study could not only facilitate improvement of the current goatpox vaccination strategy, but also provide valuable guidance to suitable candidates for evaluation and development of orthopoxvirus vaccines.

  15. A field efficacy and safety trial in the Netherlands in pigs vaccinated at 3 weeks of age with a ready-to-use porcine circovirus type 2 and Mycoplasma hyopneumoniae combined vaccine

    Directory of Open Access Journals (Sweden)

    Luuk Kaalberg

    2017-11-01

    Full Text Available Abstract Background Respiratory diseases impair the health and welfare of growing pigs and impacts farmers’ gains worldwide. Their control through a preventative medical approach has to be tailored according to the pathogens identified at farm level. In the Netherlands, several studies have emphasized the prominent role of Mycoplasma hyopneumoniae, Porcine Circovirus type 2 and Porcine Reproductive and Respiratory Syndrome Virus in such respiratory conditions. Further to the arrival on the Dutch market of the first commercially available bivalent vaccine against PCV2 and M. hyopneumoniae, Porcilis® PCV M. Hyo, a trial was designed to evaluate its safety and efficacy under local field conditions. Material and methods In a conventional farrow-to-finish 170-sow farm with a history of respiratory diseases and demonstrated circulation of both M. hyopneumoniae and PCV2, 812 piglets were randomised and included at weaning in either of the three following groups: PCVM (vaccinated with Porcilis® PCV M. Hyo, FLEX (vaccinated with CircoFLEX® and MycoFLEX® or NC (negative control, injected with placebo. Piglets were vaccinated at 3 weeks of age (day 0 and a subset was bled and weighed at regular intervals up to slaughter. Lung slaughter checks were only performed on 64% of the pigs included on day 0. Results and implication No side effect of injection was observed in any of the three groups. Average daily weight gain was improved in both vaccinated groups as compared to the NC group, over the finishing period as well as from wean-to-finish. The PCVM group had a significantly lower PCV2 viremia area under the curve than the two other groups, and a significant reduction in the severity of the pneumonia-like lesions was observed at slaughter in the pigs of the PCVM group. A conservative estimate of the economic benefit of that vaccine was 2.84 € per finisher. This trial confirms that the vaccine is efficacious against the health and growth effects of

  16. A field efficacy and safety trial in the Netherlands in pigs vaccinated at 3 weeks of age with a ready-to-use porcine circovirus type 2 and Mycoplasma hyopneumoniae combined vaccine.

    Science.gov (United States)

    Kaalberg, Luuk; Geurts, Victor; Jolie, Rika

    2017-01-01

    Respiratory diseases impair the health and welfare of growing pigs and impacts farmers' gains worldwide. Their control through a preventative medical approach has to be tailored according to the pathogens identified at farm level. In the Netherlands, several studies have emphasized the prominent role of Mycoplasma hyopneumoniae , Porcine Circovirus type 2 and Porcine Reproductive and Respiratory Syndrome Virus in such respiratory conditions. Further to the arrival on the Dutch market of the first commercially available bivalent vaccine against PCV2 and M. hyopneumoniae , Porcilis® PCV M. Hyo, a trial was designed to evaluate its safety and efficacy under local field conditions. In a conventional farrow-to-finish 170-sow farm with a history of respiratory diseases and demonstrated circulation of both M. hyopneumoniae and PCV2, 812 piglets were randomised and included at weaning in either of the three following groups: PCVM (vaccinated with Porcilis® PCV M. Hyo), FLEX (vaccinated with CircoFLEX® and MycoFLEX®) or NC (negative control, injected with placebo). Piglets were vaccinated at 3 weeks of age (day 0) and a subset was bled and weighed at regular intervals up to slaughter. Lung slaughter checks were only performed on 64% of the pigs included on day 0. No side effect of injection was observed in any of the three groups. Average daily weight gain was improved in both vaccinated groups as compared to the NC group, over the finishing period as well as from wean-to-finish. The PCVM group had a significantly lower PCV2 viremia area under the curve than the two other groups, and a significant reduction in the severity of the pneumonia-like lesions was observed at slaughter in the pigs of the PCVM group. A conservative estimate of the economic benefit of that vaccine was 2.84 € per finisher. This trial confirms that the vaccine is efficacious against the health and growth effects of PCV2 and M. hyopneumoniae , of practical advantage (single injection of a

  17. Immunogenicity and Efficacy of Live L. tarentolae Expressing KMP11-NTGP96-GFP Fusion as a Vaccine Candidate against Experimental Visceral Leishmaniasis Caused by L. infantum

    Directory of Open Access Journals (Sweden)

    Vahid NASIRI

    2016-10-01

    Full Text Available Background: The aim of present study was to evaluate the protective efficacy of live recombinant L. tarentolae expressing KMP11-NTGP96-GFP fusion as candidates for live engineered recombinant vaccine against visceral leishmaniasis in BALB/c mice.Methods: KMP-11 and NT-GP96 genes cloned into the pJET1.2/blunt cloning vector and then into pEGFP-N1 expression vector. The KMP-11, NT-GP96 and GFP fused in pEGFP-N1 and subcloned into Leishmanian pLEXSY-neo vector. Finally this construct was transferred to L. tarentolae by electroporation. Tranfection was confirmed by SDS-PAGE, WESTERN blot, flowcytometry and RT-PCR. Protective efficacy of this construct was evaluated as a vaccine candidate against visceral leishmaniasis. Parasite burden, humoral and cellular immune responses were assessed before and at 4 weeks after challenge.Results: KMP- NT-Gp96-GFP Fusion was cloned successfully into pLEXSY -neo vector and this construct successfully transferred to L. tarentolae. Finding indicated that immunization with L. tarentolae tarentolae-KMP11-NTGP96-GFP provides significant protection against visceral leishmaniasis and was able to induce an increased expression of IFN-γ and IgG2a. Following challenge, a reduced parasite load in the spleen of the KMP11-NTGP96-GFP immunized group was detected.Conclusion: The present study is the first to use a combination of a Leishmania antigen with an immunologic antigen in live recombinant L. tarentolae and results suggest that L. tarentolae-KMP11-NTGP96-GFP could be considered as a potential tool in vaccination against visceral leishmaniasis and this vaccination strategy could provide a potent rout for future vaccine development. 

  18. Classical Swine Fever—An Updated Review

    Science.gov (United States)

    Blome, Sandra; Staubach, Christoph; Henke, Julia; Carlson, Jolene; Beer, Martin

    2017-01-01

    Classical swine fever (CSF) remains one of the most important transboundary viral diseases of swine worldwide. The causative agent is CSF virus, a small, enveloped RNA virus of the genus Pestivirus. Based on partial sequences, three genotypes can be distinguished that do not, however, directly correlate with virulence. Depending on both virus and host factors, a wide range of clinical syndromes can be observed and thus, laboratory confirmation is mandatory. To this means, both direct and indirect methods are utilized with an increasing degree of commercialization. Both infections in domestic pigs and wild boar are of great relevance; and wild boars are a reservoir host transmitting the virus sporadically also to pig farms. Control strategies for epidemic outbreaks in free countries are mainly based on classical intervention measures; i.e., quarantine and strict culling of affected herds. In these countries, vaccination is only an emergency option. However, live vaccines are used for controlling the disease in endemically infected regions in Asia, Eastern Europe, the Americas, and some African countries. Here, we will provide a concise, updated review on virus properties, clinical signs and pathology, epidemiology, pathogenesis and immune responses, diagnosis and vaccination possibilities. PMID:28430168

  19. Classical Swine Fever-An Updated Review.

    Science.gov (United States)

    Blome, Sandra; Staubach, Christoph; Henke, Julia; Carlson, Jolene; Beer, Martin

    2017-04-21

    Classical swine fever (CSF) remains one of the most important transboundary viral diseases of swine worldwide. The causative agent is CSF virus, a small, enveloped RNA virus of the genus Pestivirus. Based on partial sequences, three genotypes can be distinguished that do not, however, directly correlate with virulence. Depending on both virus and host factors, a wide range of clinical syndromes can be observed and thus, laboratory confirmation is mandatory. To this means, both direct and indirect methods are utilized with an increasing degree of commercialization. Both infections in domestic pigs and wild boar are of great relevance; and wild boars are a reservoir host transmitting the virus sporadically also to pig farms. Control strategies for epidemic outbreaks in free countries ar