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

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Abstract

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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Abbreviations

Ca:

cold-adapted

CE:

embryonated chicken egg

EID50 :

50% infection dose in CE

HA:

hemagglutinin

HPAIV:

highly pathogenic avian influenza virus

IIV:

inactivated influenza vaccine

LAIV:

live attenuated influenza vaccines

LD50 :

50% lethal dose

LPAIV:

low pathogenic avian influenza virus

NA:

neuraminidase

SANP:

spherical amorphous nanoparticles consisting of birch bark triterpenoid mixture

TCID50 :

50% infection dose in tissue culture

TIV:

trivalent influenza vaccine

VAF:

virus-containing allantoic fluid

VE:

vaccine efficacy

WIV:

whole-virion inactivated vaccin

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Acknowledgements

The authors thank Dr. R. Donis (Centers for Disease Control and Prevention, Atlanta, GA, USA) for providing the vaccine strain VNH5N1-PR8/CDC-RG; Dr. Rudenko (Institute of Experimental Medicine , St. Petersburg, Russia) for providing the A/Leningrad/134/17/57 (H2N2) and A/New Caledonia-Leningrad/134/17/57 (H1N1) strains; Dr. S. S. Yamnikova (Gamaleya National Research Center for Epidemiology and Microbiology, Moscow, Russia) for providing influenza H5N1 A/chicken/Kurgan/3/2005 virus; Dr. James Robertson (National Institute for Biological Standards and Control, United Kingdom) for providing A/Nib/26/90-M (H3N2) strain; and Dr. Matrosovich (Institute of Virology, Philipps University, Marburg, Germany) for providing A/Hamburg/5/2009 (H1N1) strain.

Funding

This work was supported by the Russian Foundation for Basic Research (projects Nos. 11-04-00517-a and 17-04-00148-a).

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Authors and Affiliations

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

    E. Y. Boravleva & A. S. Gambaryan

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

    A. V. Lunitsin

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

    A. P. Kaplun & N. V. Bykova

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

    I. V. Krasilnikov

Authors
  1. E. Y. Boravleva
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  2. A. V. Lunitsin
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  3. A. P. Kaplun
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  4. N. V. Bykova
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  5. I. V. Krasilnikov
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  6. A. S. Gambaryan
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Contributions

A. P. K., I. V. K., and A. S. G. conceived and designed the experiments; E. Y. B. and A. V. L. performed the experiments; E. Y. B. and A. S. G. wrote the manuscript.

Corresponding author

Correspondence to A. S. Gambaryan.

Ethics declarations

All procedures performed with the animals were conducted according to the “International recommendations (code of ethics) for conducting biomedical research using animals” (http://www.msu.ru/bioetika/doc/recom.doc) and met the ethical standards of the institutions where the studies were carried out. The authors declare no conflict of interest.

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Disclaimer. The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the Chumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products, Russian Academy of Sciences.

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Boravleva, E., Lunitsin, A., Kaplun, A. et al. Immune Response and Protective Efficacy of Inactivated and Live Influenza Vaccines Against Homologous and Heterosubtypic Challenge. Biochemistry Moscow 85, 553–566 (2020). https://doi.org/10.1134/S0006297920050041

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