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A broadly protective therapeutic antibody against influenza B virus with two mechanisms of action

Author

Listed:
  • Ning Chai

    (Genentech)

  • Lee R. Swem

    (Genentech
    Present address: Therapeutic Antibody Department, Achaogen, South San Francisco, California 94080, USA)

  • Summer Park

    (Genentech)

  • Gerald Nakamura

    (Genentech)

  • Nancy Chiang

    (Genentech)

  • Alberto Estevez

    (Genentech)

  • Rina Fong

    (Genentech)

  • Lynn Kamen

    (Genentech)

  • Elviza Kho

    (Genentech)

  • Mike Reichelt

    (Genentech)

  • Zhonghua Lin

    (Genentech)

  • Henry Chiu

    (Genentech)

  • Elizabeth Skippington

    (Genentech)

  • Zora Modrusan

    (Genentech)

  • Jeremy Stinson

    (Genentech)

  • Min Xu

    (Genentech)

  • Patrick Lupardus

    (Genentech)

  • Claudio Ciferri

    (Genentech)

  • Man-Wah Tan

    (Genentech)

Abstract

Influenza B virus (IBV) causes annual influenza epidemics around the world. Here we use an in vivo plasmablast enrichment technique to isolate a human monoclonal antibody, 46B8 that neutralizes all IBVs tested in vitro and protects mice against lethal challenge of all IBVs tested when administered 72 h post infection. 46B8 demonstrates a superior therapeutic benefit over Tamiflu and has an additive antiviral effect in combination with Tamiflu. 46B8 binds to a conserved epitope in the vestigial esterase domain of hemagglutinin (HA) and blocks HA-mediated membrane fusion. After passage of the B/Brisbane/60/2008 virus in the presence of 46B8, we isolated three resistant clones, all harbouring the same mutation (Ser301Phe) in HA that abolishes 46B8 binding to HA at low pH. Interestingly, 46B8 is still able to protect mice against lethal challenge of the mutant viruses, possibly owing to its ability to mediate antibody-dependent cellular cytotoxicity (ADCC).

Suggested Citation

  • Ning Chai & Lee R. Swem & Summer Park & Gerald Nakamura & Nancy Chiang & Alberto Estevez & Rina Fong & Lynn Kamen & Elviza Kho & Mike Reichelt & Zhonghua Lin & Henry Chiu & Elizabeth Skippington & Zor, 2017. "A broadly protective therapeutic antibody against influenza B virus with two mechanisms of action," Nature Communications, Nature, vol. 8(1), pages 1-18, April.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms14234
    DOI: 10.1038/ncomms14234
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