Analysis of the efficacy of an adjuvant-based inactivated pandemic H5N1 influenza virus vaccine
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This paper describes a preclinical study analyzing the immunogenicity and protective efficacy of Kazfluvac®, an adjuvant-based inactivated pandemic influenza A/H5N1 virus vaccine. In this study, laboratory animals (ferrets and mice) were vaccinated by the intramuscular or intraperitoneal route at an interval of 14 days with two doses of the vaccine containing different concentrations of influenza virus hemagglutinin (HA) protein. HA protein without adjuvant (aluminum hydroxide and Merthiolate) was used as a control. As a negative control, we utilized PBS. We assessed the protective efficacy of the candidate vaccine by analyzing the response to challenge with the influenza virus strain A/chicken/Astana/6/05 (H5N1). Our experimental results revealed substantially reduced clinical disease and an increased antibody response, as determined by hemagglutination-inhibition (HAI) test and microneutralization assay (MNA). This study showed that the candidate vaccine is safe and elicits an antigen-dose-dependent serum antibody response. In summary, we determined the optimum antigen dose in a Kazfluvac® adjuvant formulation required for induction of heightened immunogenicity and protective efficacy to mitigate H5N1 disease in experimental animals, suggesting its readiness for clinical studies in humans.
We thank Zh. Kydyrbayev, Y. Kozhamkulov, D. Inkarbekov, Kairat Tabynov, and N. Assanzhanova, employees of the Research Institute for Biological Safety Problems, for their assistance in this study. The study was funded by the Science Committee of the Ministry of Education and Science of the Republic of Kazakhstan. The authors express deep gratitude to the Research Institute of Influenza (St. Petersburg, Russia) for providing the vaccine strain A/AstanaRG/6:2/2009 (H5N1) which was constructed by reverse genetics from the highly pathogenic avian influenza virus strain A/chicken/Astana/6/05 of (H5N1) and the highly reproductive influenza virus donor strain A/PR/8/34 (H1N1).
- 4.World Health Organization (2016) Cumulative number of confirmed human cases of avian influenza A/(H5N1) reported to WHO. http://www.who.int/influenza/human_animal_interface/H5N1_cumulative_table_archives/en/. Accessed 20 June 2018
- 5.Kydyrbaev ZhK, Tabynov KK, Khairullin BM (2015) Vysokopatogennyj gripp ptic: rasprostranenie v Kazahstane i razrabotka sredstv specificheskoj profilaktiki [Highly pathogenic avian influenza: distribution in Kazakhstan and development of means of specific prevention]. Almaty (in Russian) Google Scholar
- 6.Sansyzbay AR, Erofeeva MK, Khairullin BM et al (2013) Inactivated and adjuvanted whole virion clade 2.2 H5N1 (A/chicken/Astana/6/05) influenza vaccine is safe and immunogenic in a single dose in humans. Clin Vaccine Immunol 20(8):1314–1319. https://doi.org/10.1128/CVI.00096-13 CrossRefGoogle Scholar
- 7.Stukova M, Mamadaliyev S, Sandybayev N et al (2011) Basic results of development of a production technology and control of a pandemic influenza A/H5N1 vaccine. Influenza Other Respir Viruses 5(1):350–353Google Scholar
- 8.Nurpeysova A, Khairullin B, Kassenov M et al (2011) Preclinical testing of Kazfluvac®, a vaccine against pandemic influenza A/H5N1v. J Pharm Biomed Sci 1(5):108–112Google Scholar
- 19.Palmer D, Dowdle W, Coleman M et al (1975) Advanced laboratory techniques for influenza diagnosis. Immunology series no. 6. Part 2, procedural guide. US Department of Health Education and Public Health Service, Atlanta, pp 25–62Google Scholar
- 22.Ferko B, Stasakova J, Romanova J et al (2004) Immunogenicity and protection efficacy of replication-deficient influenza A viruses with altered NS1 genes. J Virol 78(23):13037–13045. https://doi.org/10.1128/JVI.78.23.13037-13045.2004 CrossRefGoogle Scholar
- 34.Johansen K, Nicoll A, Ciancio BC et al (2009) Pandemic influenza A (H1N1) 2009 vaccines in the European Union. Euro Surveill 14(41):19361Google Scholar
- 36.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(19):521–524Google Scholar
- 38.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(18):3554–3560. https://doi.org/10.1016/j.vaccine.2007.01.083 CrossRefGoogle Scholar