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Differences in the ease with which mutant viruses escape from human monoclonal antibodies against the HA stem of influenza A virus

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  • Differences in the ease with which mutant viruses escape from human monoclonal antibodies against the HA stem of influenza A virus

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    J Clin Virol. 2018 Sep 26;108:105-111. doi: 10.1016/j.jcv.2018.09.016. [Epub ahead of print]
    Differences in the ease with which mutant viruses escape from human monoclonal antibodies against the HA stem of influenza A virus.

    Yamayoshi S1, Yasuhara A1, Ito M1, Uraki R1, Kawaoka Y2.
    Author information

    Abstract

    BACKGROUND:

    Broadly protective human monoclonal antibodies that recognize the conserved epitopes in the HA of influenza A virus are being developed as therapeutic agents. Emergence of resistant viruses must always be considered when developing therapeutic agents against influenza.
    OBJECTIVES:

    We examined human hetero-reactive mAbs against the HA stem of influenza A virus for the ease with which escape mutant viruses emerged.
    STUDY DESIGN:

    We attempted to generate the mutant viruses escaped from the hetero-reactive anti-HA stem antibodies. We also evaluated their protective efficacy, binding affinity, and epitopes.
    RESULTS:

    We obtained several human monoclonal antibodies (mAbs) that react with the HA of different HA subtypes of influenza A virus belonging to group 1. Upon attempting to generate escape mutant viruses, we found that the ease with which such viruses emerged differed among the mAbs; viruses barely escaped from two of the mAbs (clones S9-3-37 and F20C77), whereas escape from the third mAb (clone F5B7) occurred readily. Comparisons of the mAbs revealed that the HA stem epitopes, in vitro neutralization potency, binding affinity to H1-HA, and protective efficacy against lethal challenge with H1N1pdm09 virus were all comparable.
    CONCLUSIONS:

    These results demonstrate the importance of determining the ease with which escape mutant viruses emerge when evaluating anti-HA stem antibodies as antiviral agents during preclinical testing.
    Copyright 2018 Elsevier B.V. All rights reserved.


    KEYWORDS:

    Escape mutant virus; HA stem; Human monoclonal antibody; Influenza A virus

    PMID: 30292135 DOI: 10.1016/j.jcv.2018.09.016
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