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).
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