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Antibodies targeting the neuraminidase active site inhibit influenza H3N2 viruses with an S245N glycosylation site

Author

Listed:
  • Daniel Stadlbauer

    (Icahn School of Medicine at Mount Sinai)

  • Meagan McMahon

    (Icahn School of Medicine at Mount Sinai)

  • Hannah L. Turner

    (The Scripps Research Institute)

  • Xueyong Zhu

    (The Scripps Research Institute)

  • Hongquan Wan

    (Center for Biologics Evaluation and Research, Food and Drug Administration)

  • Juan Manuel Carreño

    (Icahn School of Medicine at Mount Sinai)

  • George O’Dell

    (Icahn School of Medicine at Mount Sinai)

  • Shirin Strohmeier

    (Icahn School of Medicine at Mount Sinai
    University of Natural Resources and Life Sciences)

  • Zain Khalil

    (Icahn School of Medicine at Mount Sinai)

  • Marta Luksza

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • Harm Bakel

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • Viviana Simon

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai
    Molecular and Cell Based Medicine, Icahn School of Medicine at Mount Sinai
    Center for Vaccine Research and Pandemic Preparedness (C-VaRPP), Icahn School of Medicine at Mount Sinai)

  • Ali H. Ellebedy

    (Washington University School of Medicine)

  • Ian A. Wilson

    (The Scripps Research Institute
    The Scripps Research Institute)

  • Andrew B. Ward

    (The Scripps Research Institute)

  • Florian Krammer

    (Icahn School of Medicine at Mount Sinai
    Molecular and Cell Based Medicine, Icahn School of Medicine at Mount Sinai
    Center for Vaccine Research and Pandemic Preparedness (C-VaRPP), Icahn School of Medicine at Mount Sinai)

Abstract

Contemporary influenza A H3N2 viruses circulating since 2016 have acquired a glycosylation site in the neuraminidase in close proximity to the enzymatic active site. Here, we investigate if this S245N glycosylation site, as a result of antigenic evolution, can impact binding and function of human monoclonal antibodies that target the conserved active site. While we find that a reduction in the inhibitory ability of neuraminidase active site binders is measurable, this class of broadly reactive monoclonal antibodies maintains protective efficacy in vivo.

Suggested Citation

  • Daniel Stadlbauer & Meagan McMahon & Hannah L. Turner & Xueyong Zhu & Hongquan Wan & Juan Manuel Carreño & George O’Dell & Shirin Strohmeier & Zain Khalil & Marta Luksza & Harm Bakel & Viviana Simon &, 2022. "Antibodies targeting the neuraminidase active site inhibit influenza H3N2 viruses with an S245N glycosylation site," Nature Communications, Nature, vol. 13(1), pages 1-8, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-35586-7
    DOI: 10.1038/s41467-022-35586-7
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