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Strengthening the Effectiveness of the Candidate Influenza Vaccine by Combining Conserved Sequences of Hemagglutinin and M2 protein

https://doi.org/10.31631/2073-3046-2017-16-3-65-70

Abstract

The development of universal influenza vaccine - a vaccine directed to all subtypes of human influenza A viruses - is the really actual problem task. This paper presents the comparative characteristic of the specific activity of various recombinant proteins consisting of antigenic determinants of influenza A virus - the ectodomain of the M2 protein (M2e) and a fragment of the second subunit of the hemagglutinin (the amino acid sequence 76 - 130). Flagellin - Salmonella typhimurium protein was used as carrier protein and as adjuvant. We use two forms of flagellin: full size and with deleted hypervariable region. The proteins showed high immunogenicity, and the ability to prevent lethal infection of influenza virus in mice. Full-length flagellin with HA2 (76 - 130) and M2e on the C-terminus (protein Flg-HA2-4M2e) demonstrated the most protective properties. It provides 100% survival immunized mice that were challenge with a high dose of influenza A (H3N2) - 10 LD50. Proteins containing only full sized flagellin with M2e or flagellin truncated form with M2e at the C-terminus and HA2 within the hypervariable region, protected 75% of animals from lethal infection. Protein Flg-HA2-4M2e is promising for further study as a vaccine.

About the Authors

L. M. Tsybalova
Federal State Budget Institution Research «Institute of Influenza» of the Ministry of Healthcare of the Russian Federation
Russian Federation


L. A. Stepanova
Federal State Budget Institution Research «Institute of Influenza» of the Ministry of Healthcare of the Russian Federation
Russian Federation


R. Yu. Kotlyarov
Federal State Institution «The Federal Research Centre «Fundamentals of Biotechnology» of the Russian Academy of Sciences
Russian Federation


E. A. Blokhina
Federal State Institution «The Federal Research Centre «Fundamentals of Biotechnology» of the Russian Academy of Sciences
Russian Federation


M. A. Shuklina
Federal State Budget Institution Research «Institute of Influenza» of the Ministry of Healthcare of the Russian Federation
Russian Federation


E. S. Mardanova
Federal State Institution «The Federal Research Centre «Fundamentals of Biotechnology» of the Russian Academy of Sciences
Russian Federation


A. V. Korotkov
Federal State Budget Institution Research «Institute of Influenza» of the Ministry of Healthcare of the Russian Federation
Russian Federation


M. V. Potapchuk
Federal State Budget Institution Research «Institute of Influenza» of the Ministry of Healthcare of the Russian Federation
Russian Federation


N. V. Ravin
Federal State Institution «The Federal Research Centre «Fundamentals of Biotechnology» of the Russian Academy of Sciences
Russian Federation


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Review

For citations:


Tsybalova L.M., Stepanova L.A., Kotlyarov R.Yu., Blokhina E.A., Shuklina M.A., Mardanova E.S., Korotkov A.V., Potapchuk M.V., Ravin N.V. Strengthening the Effectiveness of the Candidate Influenza Vaccine by Combining Conserved Sequences of Hemagglutinin and M2 protein. Epidemiology and Vaccinal Prevention. 2017;16(3):65-70. (In Russ.) https://doi.org/10.31631/2073-3046-2017-16-3-65-70

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ISSN 2073-3046 (Print)
ISSN 2619-0494 (Online)