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A Potent Germline-like Human Monoclonal Antibody Targets a pH-Sensitive Epitope on H7N9 Influenza Hemagglutinin

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  • A Potent Germline-like Human Monoclonal Antibody Targets a pH-Sensitive Epitope on H7N9 Influenza Hemagglutinin

    Cell Host Microbe. 2017 Sep 27. pii: S1931-3128(17)30344-X. doi: 10.1016/j.chom.2017.08.011. [Epub ahead of print]
    A Potent Germline-like Human Monoclonal Antibody Targets a pH-Sensitive Epitope on H7N9 Influenza Hemagglutinin.

    Yu F1, Song H2, Wu Y3, Chang SY4, Wang L3, Li W5, Hong B3, Xia S3, Wang C3, Khurana S6, Feng Y5, Wang Y5, Sun Z3, He B3, Hou D7, Manischewitz J6, King LR6, Song Y7, Min JY4, Golding H6, Ji X2, Lu L3, Jiang S3, Dimitrov DS5, Ying T8.
    Author information

    Abstract

    The H7N9 influenza virus causes high-mortality disease in humans but no effective therapeutics are available. Here we report a human monoclonal antibody, m826, that binds to H7 hemagglutinin (HA) and protects against H7N9 infection. m826 binds to H7N9 HA with subnanomolar affinity at acidic pH and 10-fold lower affinity at neutral pH. The high-resolution (1.9 ?) crystal structure of m826 complexed with H7N9 HA indicates that m826 binds an epitope that may be fully exposed upon pH-induced conformational changes in HA. m826 fully protects mice against lethal challenge with H7N9 virus through mechanisms likely involving antibody-dependent cell-mediated cytotoxicity. Interestingly, immunogenetic analysis indicates that m826 is a germline antibody, and m826-like sequences can be identified in H7N9-infected patients, healthy adults, and newborn babies. These m826 properties offer a template for H7N9 vaccine immunogens, a promising candidate therapeutic, and a tool for exploring mechanisms of virus infection inhibition by antibodies.
    Copyright ? 2017 Elsevier Inc. All rights reserved.


    KEYWORDS:

    ADCC; H7N9 influenza; germline; hemagglutinin; monoclonal antibody

    PMID: 28966056 DOI: 10.1016/j.chom.2017.08.011
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