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Microbiology Independent Research Journal (MIR Journal)

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H5N1 influenza vaccine quality is affected by hemagglutinin conformational stability

https://doi.org/10.18527/2500-2236-2014-1-1-12-26

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Аннотация

Since 1997, highly pathogenic H5N1 avian influenza viruses have circulated in wild and domestic birds and sporadically have infected humans. Conventional inactivated vaccines made from these viruses were shown to have decreased HA content and immunogenicity compared to seasonal preparations. We assumed that the high pH threshold (5.6-6.0) known for the HA conformational change (pH of fusion or activation) of avian highly pathogenic influenza viruses resulted in the low stability of native HA conformation and affected the vaccine quality. The 58Lys→Ile mutation introduced into the HA2 subunit of the HA of A/chicken/Kurgan/5/05 (H5N1) virus decreased the pH threshold of the HA activation. The mutant virus demonstrated increased HA stability toward acidic pH and elevated temperature, decreased binding efficiency to the monoclonal antibody IIF4 that recognizes the HA low pH form, and increased HA resistance to trypsin digestion. Virus with modified HA was less susceptible to freezing stress and showed an increased content of immunocompetent HA in inactivated vaccine preparation compared to the analogous virus with original HA. Therefore, we have shown a way to increase the quality of inactivated vaccines made from highly pathogenic avian influenza viruses.

Ключевые слова


Об авторах

М. Sergeeva
Research Institute of Influenza
Россия
Russian Federation 197376, Saint Petersburg, Prof. Popova str., 15/17


А. Krokhin
Green Hills Biotechnology AG
Австрия
Vienna, Austria


М. Matrosovich
Institute of Virology, Philipp University of Marburg
Германия
Marburg, Germany


Т. Matrosovich
Institute of Virology, Philipp University of Marburg
Германия
Marburg, Germany


M. Wolschek
Green Hills Biotechnology AG
Австрия
Vienna, Austria


O. Kiselev
Research Institute of Influenza
Россия
Saint Petersburg, Russian Federation


J. Romanova
Research Institute of Influenza; Green Hills Biotechnology AG
Россия
Saint Petersburg, Russian Federation; Vienna, Austria


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Для цитирования:


Sergeeva М., Krokhin А., Matrosovich М., Matrosovich Т., Wolschek M., Kiselev O., Romanova J. H5N1 influenza vaccine quality is affected by hemagglutinin conformational stability. Microbiology Independent Research Journal (MIR Journal). 2014;1(1):12-21. https://doi.org/10.18527/2500-2236-2014-1-1-12-26

For citation:


Sergeeva M., Krokhin A., Matrosovich M., Matrosovich T., Wolschek M., Kiselev O., Romanova J. H5N1 influenza vaccine quality is affected by hemagglutinin conformational stability. Microbiology Independent Research Journal (MIR Journal). 2014;1(1):12-21. https://doi.org/10.18527/2500-2236-2014-1-1-12-26

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ISSN 2500-2236 (Online)