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A broadly protective human antibody for GI genogroup noroviruses

  1. Author:
    Rimkute, Inga
    Olia, Adam S
    Suleiman, Mehin
    Woods, Kamron D
    Bylund, Tatsiana
    Morano, Nicholas C
    Tully, Ena S
    Verardi, Raffaello
    Bao, Saran
    Beddall, Margaret H
    Chaimongkol, Natthawan
    Donaldson, Mitzi M
    Du, Renguang
    Dulan, Caitlyn N M
    Gorman, Jason [ORCID]
    Henry, Amy R
    Schramm, Chaim A [ORCID]
    Sosnovtsev, Stanislav V
    Stephens,Tyler
    Todd, John-Paul
    Tsybovsky,Yaroslav [ORCID]
    Douek, Daniel C [ORCID]
    Green, Kim Y
    Rawi, Reda [ORCID]
    Shapiro, Lawrence
    Zhou, Tongqing [ORCID]
    Kwong, Peter D [ORCID]
    Roederer, Mario [ORCID]

  2. Author Address

    Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA., Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY, USA., Department of Biochemistry and Molecular Biophysics, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA., Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA., Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA., Electron Microscopy Laboratory, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Frederick, MD, USA., Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA. pdk3@cumc.columbia.edu., Department of Biochemistry and Molecular Biophysics, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA. pdk3@cumc.columbia.edu., Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA. pdk3@cumc.columbia.edu., Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA. roederer@nih.gov.,
    1. Year: 2025
    2. Date: Apr 10
    3. Epub Date: 2025 04 10
  2. Journal: Nature Microbiology
  4. Type of Article: Article
  1. Abstract:

    Noroviruses infect millions each year, and while effective countermeasures are eagerly sought, none have been reported for the GI genogroup, first described more than 50?years ago. Here, to provide insight into GI norovirus neutralization, we isolated a broad GI antibody, 16E10, from a human blood donor and showed it neutralizes noroviruses in human enteroid cultures and abrogates or reduces infection in rhesus macaques. The cryogenic electron microscopy reconstruction of 16E10 with a norovirus protruding-domain dimer at 2.56-Å resolution reveals an exceptionally large binding surface, overlapping an antibody supersite, distal from host receptor-binding or cofactor-binding sites. Cryogenic electron microscopy reconstructions with virus-like particles (VLPs) showed that 16E10 disrupts protruding domains on the VLP surface and disassembles VLPs, altering viral organization required for avidity. While its epitope was generally conserved, 16E10 recognized multiple sequence-divergent residues, binding to which was enabled by corresponding cavities in the 16E10-norovirus interface. Broad recognition of noroviruses can thus incorporate sequence-divergent residues, through a cavity-based mechanism of diversity tolerance. © 2025. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.

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External Sources

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  2. DOI: 10.1038/s41564-025-01952-6
  3. PMID: 40211068
  4. PII : 10.1038/s41564-025-01952-6

Library Notes

  1. Fiscal Year: FY2024-2025
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