Virologica Sinica

, Volume 27, Issue 6, pp 344–351 | Cite as

Immunogenic and protective properties of the first kazakhstan vaccine against pandemic influenza A (H1N1) pdm09 in Ferrets

  • Kaissar Tabynov
  • Zhailaubai Kydyrbayev
  • Abylai Sansyzbay
  • Berik Khairullin
  • Sholpan Ryskeldinova
  • Nurika Assanzhanova
  • Yerken Kozhamkulov
  • Dulat Inkarbekov
Research Article

Abstract

This paper presents the results of a pre-clinical study of the immunogenicity and efficacy of an egg-derived, inactivated, whole-virion adjuvanted vaccine (Refluvac®) on ferret models. For this purpose, groups of eight ferrets (6 to 7 months old) were injected with 0.5 mL of vaccine specimens containing 3.75, 7.5 or 15.0 μg of virus hemagglutinin. Administration was intramuscular and given either as a single dose or as two doses 14 days apart. All vaccine specimens manifested immunogenicity in ferrets for single (HI titer, from 51 ± 7 to 160 ± 23) and double (HI titer, from 697 ± 120 to 829 ± 117) administrations. To assess the protective effects of the vaccine, ferrets from the vaccinated and control groups were infected intranasally with pandemic virus A/California/7/09 (H1N1) pdm09 at a dose of 106 EID50/0.5 mL. Fourteen days post-infection, the ferrets inoculated with single or double vaccines containing 3.75, 7.5 or 15.0 μg of hemagglutinin per dose showed no signs of influenza infection, weight loss, or body temperature rise, and no premature deaths occurred. The number of vaccinated ferrets shedding the virus via the upper airway, as well as the amount of virus shed after infection, was significantly reduced in comparison with animals from the control group. Based on our results, we suggest that a single vaccination at a dose of 3.75 or 7.5 μg hemagglutinin be used for Phase I clinical trials.

Keywords

Vaccine Pandemic Influenza A (H1N1) pdm09 Immunogenic and Protective Properties Ferrets 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Ehrlich H J, Müller M, Fritsch S, et al. 2009. A cell culture (Vero)-derived H5N1 whole-virus vaccine induces cross-reactive memory responses. J Infect Dis, 200(7): 1113–1118.PubMedCrossRefGoogle Scholar
  2. 2.
    European Union Health Security Committee (HSC)/Early Warning and Response System (EWRS). 2009. HSC/EWRS statement on influenza A(H1N1) 2009: target and priority groups for vaccination. http://ec.europa.eu/health/ph_threats/com/Influenza/docs/HSC_EWRS_statement_en.pdf
  3. 3.
    Jain F S, Finelli L, Shaw M W, et al. 2009. Emergence of a novel swine-origin influenza A (H1N1) virus in humans. N Engl J Med, 360: 2605–2615.PubMedCrossRefGoogle Scholar
  4. 4.
    Johansen K, Nicoll A, Ciancio B C, et al. 2009. Pandemic influenza A(H1N1) 2009 vaccines in the European Union. Euro Surveill, 14(41): 19361.PubMedGoogle Scholar
  5. 5.
    Katz J, Hancock K, Veguilla V, et al. 2009. Serum cross-reactive antibody response to a novel influenza A (H1N1) virus after vaccination with seasonal influenza vaccine. MMWR Morb Mortal Wkly Rep, 58: 521–524.Google Scholar
  6. 6.
    Li J, Shao T J, Yu X F, Pan J C, et al. 2012. Molecular evolution of HA gene of the influenza A H1N1 pdm09 strain during the consecutive seasons 2009–2011 in Hangzhou, China: Several immune-escape variants without positively selected sites. J Clin Virol, [Epub ahead of print].Google Scholar
  7. 7.
    Lin J, Zhang J, Dong X, et al. 2006. Safety and immunogenicity of an inactivated adjuvanted whole-virion influenza A (H5N1) vaccine: a phase I randomised controlled trial. Lancet, 368: 991–997.PubMedCrossRefGoogle Scholar
  8. 8.
    Maher J A, DeStefano J. 2004. The ferret: an animal model to study influenza virus. Lab Anim (NY), 33: 50–53.CrossRefGoogle Scholar
  9. 9.
    Mamadalyiev S, Nurpeysova A, Khairullin B, et al. 2011. Preclinical Testing of Refluvac®, A vaccine against pandemic influenza A/H1N1v. J Appl Environ Biol Sci, 1(3): 48–53.Google Scholar
  10. 10.
    Ninomiya A, Imai M, Tashiro M, et al. 2007. Inactivated influenza H5N1 whole-virus vaccine with aluminum adjuvant induces homologous and heterologous protective immunities against lethal challenge with highly pathogenic H5N1 avian influenza viruses in a mouse model. Vaccine, 25: 3554–3560.PubMedCrossRefGoogle Scholar
  11. 11.
    Palmer D F, Dowdle W R, Coleman M T, et al. 1975. Advanced laboratory techniques for influenza diagnosis. Immun Ser, 6: 25–45.Google Scholar
  12. 12.
    Pascua P N Q, Song M-S, Lee J H, et al. 2009. Evaluation of the efficacy and cross-protectivity of recent human and swine vaccines against the pandemic (H1N1) 2009 virus infection. PLoS ONE, 4(12): e8431.PubMedCrossRefGoogle Scholar
  13. 13.
    Reed L J, Muench H. 1938. A simple method of estimating fifty percent endpoints. Am J Hyg, 27: 493–497.Google Scholar
  14. 14.
    Ruat C, Caillet C, Bidaut A, et al. 2008. Vaccination of macaques with adjuvanted formalin-inactivated influenza A virus (H5N1) vaccines: protection against H5N1 challenge without disease enhancement. J Virol, 82: 2565–2569.PubMedCrossRefGoogle Scholar
  15. 15.
    Subbarao K, Luke C. 2007. H5N1 viruses and vaccines. PLoS Pathog, 3(3): e40.PubMedCrossRefGoogle Scholar
  16. 16.
    Vajo Z, Kosa L, Visontay I, et al. 2007. Inactivated Whole Virus Influenza A (H5N1) Vaccine. Emerg Infect Dis, 13(5): 807–808.PubMedCrossRefGoogle Scholar
  17. 17.
    WHO. 2010. Pandemic (H1N1) 2009: update 106. http://www.who.int/csr/don/2010_06_25/en/index.html.
  18. 18.
    WHO. 2002. WHO manual on animal influenza diagnosis and surveillance. Geneva: World Health Organization.Google Scholar
  19. 19.
    Wood J M, Schild G C, Newman R W, et al. 1977. An improved single radial-immunodiffusion technique for the assay of influenza haemagglutinin antigen: application for potency determinations of inactivated whole virus and subunit vaccines. J Biol Stand, 5: 237–247.PubMedCrossRefGoogle Scholar
  20. 20.
    Zimmer S M, Burke D S. 2009. Historical perspective — emergence of influenza A(H1N1) viruses. N Engl J Med, 361: 279–285.PubMedCrossRefGoogle Scholar

Copyright information

© Wuhan Institute of Virology, CAS and Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Kaissar Tabynov
    • 1
  • Zhailaubai Kydyrbayev
    • 1
  • Abylai Sansyzbay
    • 1
  • Berik Khairullin
    • 1
  • Sholpan Ryskeldinova
    • 1
  • Nurika Assanzhanova
    • 1
  • Yerken Kozhamkulov
    • 1
  • Dulat Inkarbekov
    • 1
  1. 1.Research Institute for Biological Safety Problems (RIBSP)GvardeiskiKazakhstan

Personalised recommendations