Immune Response and Protective Efficacy of Inactivated and Live Influenza Vaccines Against Homologous and Heterosubtypic Challenge

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E. Y. Boravleva¹, A. V. Lunitsin², A. P. Kaplun³, N. V. Bykova³, I. V. Krasilnikov⁴, and A. S. Gambaryan^1,a*

¹Chumakov Federal Scientific Center for Research and Development of Immune and Biological Products, Russian Academy of Sciences, 108819 Moscow, Russia

²FSBSI Federal Research Center for Virology and Microbiology, 601125 Volginsky, Vladimir Region, Russia

³Lomonosov Moscow University of Fine Chemical Technology, 119571 Moscow, Russia

⁴Saint Petersburg Institute of Vaccines and Sera, FMBA, 198320 St.-Petersburg, Russia

^* To whom correspondence should be addressed.

Received February 19, 2020; Revised March 19, 2020; Accepted March 20, 2020

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Inactivated (whole-virion, split, subunit, and adjuvanted) vaccines and live attenuated vaccine were tested in parallel to compare their immunogenicity and protective efficacy. Homologous and heterosubtypic protection against the challenge with influenza H5N1 and H1N1 viruses in a mouse model were studied. Single immunization with live or inactivated whole-virion H5N1 vaccine elicited a high level of serum antibodies and provided complete protection against the challenge with the lethal A/Chicken/Kurgan/3/05 (H5N1) virus, whereas application of a single dose of the split vaccine was much less effective. Adjuvants increased the antibody levels. Addition of the Iso-SANP adjuvant to the split vaccine led to a paradoxical outcome: it increased the antibody levels but reduced the protective effect of the vaccine. All tested adjuvants shifted the ratio between IgG1 and IgG2a antibodies. Immunization with any of the tested heterosubtypic live viruses provided partial protection against the H5N1 challenge and significantly reduced mouse mortality, while inactivated H1N1 vaccine offered no protection at all. More severe course of illness and earlier death were observed in mice after immunization with adjuvanted subunit vaccines followed by the challenge with the heterosubtypic virus compared to challenged unvaccinated animals.

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KEY WORDS: influenza virus A, live and inactivated vaccine, adjuvants

DOI: 10.1134/S0006297920050041

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