Cross-lineage protection by human antibodies binding the influenza B hemagglutinin

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    Author
    Liu, Y; Tan, H-X; Koutsakos, M; Jegaskanda, S; Esterbauer, R; Tilmanis, D; Aban, M; Kedzierska, K; Hurt, AC; Kent, SJ; ...
    Date
    2019-01-18
    Source Title
    Nature Communications
    Publisher
    NATURE PUBLISHING GROUP
    University of Melbourne Author/s
    Wheatley, Adam; Kent, Stephen; Kedzierska, Katherine; Jegaskanda, Sinthujan; Hurt, Aeron; Tan, Hyon Xhi; Esterbauer, Robyn; Koutsakos, Marios; Liu, Yi; Tilmanis, Danielle; ...
    Affiliation
    Microbiology and Immunology
    Melbourne School of Population and Global Health

    Doherty Institute
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    Document Type
    Journal Article
    Citations
    Liu, Y., Tan, H. -X., Koutsakos, M., Jegaskanda, S., Esterbauer, R., Tilmanis, D., Aban, M., Kedzierska, K., Hurt, A. C., Kent, S. J. & Wheatley, A. K. (2019). Cross-lineage protection by human antibodies binding the influenza B hemagglutinin. NATURE COMMUNICATIONS, 10 (1), https://doi.org/10.1038/s41467-018-08165-y.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/253570
    DOI
    10.1038/s41467-018-08165-y
    NHMRC Grant code
    NHMRC/1129099
    Abstract
    Influenza B viruses (IBV) drive a significant proportion of influenza-related hospitalisations yet are understudied compared to influenza A. Current vaccines target the head of the viral hemagglutinin (HA) which undergoes rapid mutation, significantly reducing vaccine effectiveness. Improved vaccines to control IBV are needed. Here we developed novel IBV HA probes to interrogate humoral responses to IBV in humans. A significant proportion of IBV HA-specific B cells recognise both B/Victoria/2/87-like and B/Yamagata/16/88-like lineages in a distinct pattern of cross-reactivity. Monoclonal antibodies (mAbs) were reconstituted from IBV HA-specific B cells, including mAbs providing broad protection in murine models of lethal IBV infection. Protection was mediated by neutralising antibodies targeting the receptor binding domain, or via Fc-mediated functions of non-neutralising antibodies binding alternative epitopes including the IBV HA stem. This work defines antigenic cross-recognition between IBV lineages and provides guidance for the rational design of improved IBV vaccines for broad and durable protection.

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