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

Author

Listed:
  • Yi Liu

    (University of Melbourne)

  • Hyon-Xhi Tan

    (University of Melbourne)

  • Marios Koutsakos

    (University of Melbourne)

  • Sinthujan Jegaskanda

    (University of Melbourne)

  • Robyn Esterbauer

    (University of Melbourne)

  • Danielle Tilmanis

    (The Peter Doherty Institute for Infection and Immunity)

  • Malet Aban

    (The Peter Doherty Institute for Infection and Immunity)

  • Katherine Kedzierska

    (University of Melbourne)

  • Aeron C. Hurt

    (University of Melbourne
    The Peter Doherty Institute for Infection and Immunity)

  • Stephen J. Kent

    (University of Melbourne
    Monash University
    University of Melbourne)

  • Adam K. Wheatley

    (University of Melbourne)

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.

Suggested Citation

  • Yi Liu & Hyon-Xhi Tan & Marios Koutsakos & Sinthujan Jegaskanda & Robyn Esterbauer & Danielle Tilmanis & Malet Aban & Katherine Kedzierska & Aeron C. Hurt & Stephen J. Kent & Adam K. Wheatley, 2019. "Cross-lineage protection by human antibodies binding the influenza B hemagglutinin," Nature Communications, Nature, vol. 10(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-018-08165-y
    DOI: 10.1038/s41467-018-08165-y
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