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Genome Biol Evol: Genome-wide analysis of evolutionary markers of human influenza A(H1N1)pdm09 and A(H3N2) viruses may guide selection of vaccine strain candidates

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  • Genome Biol Evol: Genome-wide analysis of evolutionary markers of human influenza A(H1N1)pdm09 and A(H3N2) viruses may guide selection of vaccine strain candidates

    Genome Biol Evol (2015) doi: 10.1093/gbe/evv240
    Genome-wide analysis of evolutionary markers of human influenza A(H1N1)pdm09 and A(H3N2) viruses may guide selection of vaccine strain candidates

    • 1 Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Finland;
    • 2 Department of Public Health, Hjelt Institute, University of Helsinki, Finland;
    • 3 Welcome Trust Sanger Institute, United Kingdom;
    • 4 Institute of Biomedicine, Pharmacology, University of Helsinki, Helsinki, Finland;
    • 5 Department of Laboratory Medicine, National University Hospital, National University Health System, Singapore;
    • 6 Clinical Microbiology, University Hospitals of Leicester NHS Trust, UK.
    • * Author for Correspondence: Denis E. Kainov, Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Finland, Tel: +358504155460; Fax: +3581912 5737; Email: denis.kainov{at}helsinki.fi
    • Received October 20, 2015.
    • Revision received November 10, 2015.
    • Accepted November 23, 2015.


    Abstract

    Here we analysed whole-genome sequences of 3969 influenza A(H1N1)pdm09 and 4774 A(H3N2) strains which circulated during 2009-2015 in the world. The analysis revealed changes at 481 and 533 amino acid sites in proteins of influenza A(H1N1)pdm09 and A(H3N2) strains, respectively. Many of these changes were introduced as a result of random drift. However, there were 61 and 68 changes which were present in relatively large number of A(H1N1)pdm09 and A(H3N2) strains which circulated during relatively long time. We named these amino acids substitutions evolutionary markers, as they seemed to contain valuable information regarding the viral evolution. Interestingly, influenza A(H1N1)pdm09 and A(H3N2) viruses acquired non-overlapping sets of evolutionary markers. We next analysed these characteristic markers in vaccine strains recommended by World Health Organization (WHO) for the five past years. Our analysis revealed that vaccine strains carried only few evolutionary markers at antigenic sites of viral hemagglutinin (HA) and neuraminidase (NA). The absence of these markers at antigenic sites could affect the recognition of HA and NA by human antibodies generated in response to vaccinations. This could, in part, explain moderate efficacy of influenza vaccines during 2009-2014. Finally, we identified influenza A(H1N1)pdm09 and A(H3N2) strains, which contain all the evolutionary markers of influenza A strains circulated in 2015, and which could be used as vaccine candidates for the 2015/2016 season. Thus, genome-wide analysis of evolutionary markers of influenza A(H1N1)pdm09 and A(H3N2) viruses may guide selection of vaccine strain candidates.



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