ArticleCell host & microbe2023
Rare, convergent antibodies targeting the stem helix broadly neutralize diverse betacoronaviruses.
Erratum issuedOpen access · hybridAbstract read
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Article in Cell host & microbe, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 45 papers.
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45citing papers in PubMed
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Who cites it
45 citing papers in PubMed, 62 citations in OpenAlex.
- Directed evolution of a stem-helix-targeting antibody enables MERS-CoV cross-neutralization through enhanced binding affinity.PLoS pathogens · 2026Article
- Broad Neutralizing Antibodies Against SARS-CoV-2: Current Progress and Engineering Strategies.Viruses · 2026Review
- SARS-CoV-2 fusion-peptide-directed antibodies are elicited by natural infection and can mediate broad sarbecovirus neutralization.Cell reports · 2026Article
- The buried S2 apex of SARS-CoV-2 spike elicits an immunodominant germline-restricted public antibody response.bioRxiv : the preprint server for biology · 2026Article
- Heterologous betacoronavirus spike immunization in nonhuman primates elicits cross-reactive antibodies that neutralize both sarbeco- and merbecoviruses.bioRxiv : the preprint server for biology · 2026Article
- Preclinical development of a cross-protective β-SARS-CoV-2 virus-like particle vaccine adjuvanted with MF59.NPJ vaccines · 2026Article
- Confronting the known unknown: historical lessons and future strategies for Disease X.Frontiers in public health · 2026Review
- Human Coronavirus HKU1 Neutralizing Monoclonal Antibodies Target Diverse Epitopes Within and Around the TMPRSS2 Receptor Binding Site.bioRxiv : the preprint server for biology · 2025Article
- Directed evolution of a stem-helix-targeting antibody enables MERS-CoV cross-neutralization through enhanced binding affinity.bioRxiv : the preprint server for biology · 2025Article
- Coordinated early immune response in the lungs is required for effective control of SARS-CoV-2 replication.Nature communications · 2025Article
- Germline-encoded recognition of peanut underlies development of convergent antibodies in humans.Science translational medicine · 2025Article
- Ultrapotent SARS coronavirus-neutralizing single-domain antibodies that clamp the spike at its base.Nature communications · 2025Article
- Review
- Potent neutralising monoclonal antibodies targeting the spike of NL63 coronavirus.Npj viruses · 2025Article
- Efficient boosting of Omicron-reactive memory B cells after breakthrough infection protects from repeated exposure.iScience · 2025Article
- Structural basis and mode of action for two broadly neutralizing nanobodies targeting the highly conserved spike stem-helix of sarbecoviruses including SARS-CoV-2 and its variants.PLoS pathogens · 2025Article
- RBD-depleted SARS-CoV-2 spike generates protective immunity in cynomolgus macaques.NPJ vaccines · 2025Article
- Post-transfusion activation of coagulation pathways during severe COVID-19 correlates with COVID-19 convalescent plasma antibody profiles.The Journal of clinical investigation · 2025Article
- SARS-CoV-2 Fusion Peptide-Directed Antibodies Elicited by Natural Infection Mediate Broad Sarbecovirus Neutralization.medRxiv : the preprint server for health sciences · 2025Article
- Disease diagnostics using machine learning of B cell and T cell receptor sequences.Science (New York, N.Y.) · 2025Article
Corrections and comments
- Erratum issued
Authors and funding
44 authors at 6 institutions in 1 country.
Cherrelle DaconAntibody Biology Unit, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA.
Linghang PengDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Ting-Hui LinDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Courtney TuckerAntibody Biology Unit, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA; Department of Biology, The Catholic University of America, Washington, DC 20064, USA.
Chang-Chun D LeeDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Yu CongIntegrated Research Facility, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702, USA.
Lingshu WangVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Lauren PurserAntibody Biology Unit, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA.
Andrew J R CooperAntibody Biology Unit, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA.
Jazmean K WilliamsIntegral Molecular, Philadelphia, PA 19104, USA.
Chul-Woo PyoClinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Meng YuanDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Ivan KosikCellular Biology Section, Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Zhe HuCellular Biology Section, Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Ming ZhaoProtein Chemistry Section, Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA.
Divya MohanAntibody Biology Unit, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA.
Mary PetersonMalaria Infection Biology and Immunity Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA.
Jeff SkinnerMalaria Infection Biology and Immunity Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA.
Saurabh DixitIntegrated Research Facility, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702, USA.
Erin KollinsIntegrated Research Facility, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702, USA.
Louis HuzellaIntegrated Research Facility, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702, USA.
Donna PerryIntegrated Research Facility, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702, USA.
Russell ByrumIntegrated Research Facility, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702, USA.
Sanae LembirikIntegrated Research Facility, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702, USA.
Michael MurphyIntegrated Research Facility, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702, USA.
Yi ZhangVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Eun Sung YangVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Man ChenVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Kwanyee LeungVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Rona S WeinbergNew York Blood Center, Lindsley F. Kimball Research Institute, New York, NY 10065, USA.
Amarendra PeguVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Daniel E GeraghtyClinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Edgar DavidsonIntegral Molecular, Philadelphia, PA 19104, USA.
Benjamin J DoranzIntegral Molecular, Philadelphia, PA 19104, USA.
Iyadh DouagiFlow Cytometry Section, Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Susan MoirB Cell Immunology Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Jonathan W YewdellCellular Biology Section, Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Connie SchmaljohnIntegrated Research Facility, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702, USA.
Peter D CromptonMalaria Infection Biology and Immunity Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA.
John R MascolaVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Michael R HolbrookIntegrated Research Facility, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702, USA.
David NemazeeDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Ian A WilsonDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA; The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Joshua TanAntibody Biology Unit, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA. Electronic address: tanj4@nih.gov.
National Institutes of Health · USScripps Research Institute · USIntegral Molecular (United States) · USFred Hutch Cancer Center · USNational Institute of Allergy and Infectious Diseases · USNew York Blood Center · US
Funding
Infectious Diseases Research Technologies Core - BethesdaZICAI001051 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI CHERRY, JAMES · 2009 to 2025
$226.1MX-ray Absorption Spectroscopy (XAS) pp.711-759P41GM103393 · NIGMS · STANFORD UNIVERSITY · PI HODGSON, KEITH O · 2012 to 2019
$30.6MB-Cell Epitope Discovery and Mechanisms of Antibody Protection for ZIKV, MARV, VEEV Envelope Proteins 75N93019C00073 · NIAID · INTEGRAL MOLECULAR · PI DORANZ, BENJAMIN · 2019 to 2023
$7.5MGermline targeting influenza immunogensR01AI132317 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI NEMAZEE, DAVID · 2017 to 2021
$7.0MHuman monoclonal antibodies against SARS-CoV-2ZIAAI001285 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI TAN, JOSHUA · 2020 to 2025
$4.9MSARS-CoV2 Immunity and Cell BiologyZIAAI001320 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI YEWDELL, JONATHAN W · 2020 to 2024
$1.7MImmunologic Studies Associated with COVID-19 ZIAAI001325 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI MOIR, SUSAN · 2020 to 2025
$1.3MDevelopment of the golden Syrian hamster model of COVID-19ZIGAI009011 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI SCHMALJOHN, CONNIE · 2020 to 2021
$1.1MEvaluation of COVID-19 antibody therapiesZIGAI009010 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI SCHMALJOHN, CONNIE · 2020 to 2021
$242kNIAID NIH HHS 75N93019C00073NIAID NIH HHS HHSN272201800013CNIAID NIH HHS R01 AI132317NIGMS NIH HHS P41 GM103393
Abstract
Humanity has faced three recent outbreaks of novel betacoronaviruses, emphasizing the need to develop approaches that broadly target coronaviruses. Here, we identify 55 monoclonal antibodies from COVID-19 convalescent donors that bind diverse betacoronavirus spike proteins. Most antibodies targeted an S2 epitope that included the K814 residue and were non-neutralizing. However, 11 antibodies targeting the stem helix neutralized betacoronaviruses from different lineages. Eight antibodies in this group, including the six broadest and most potent neutralizers, were encoded by IGHV1-46 and IGKV3-20. Crystal structures of three antibodies of this class at 1.5-1.75-Å resolution revealed a conserved mode of binding. COV89-22 neutralized SARS-CoV-2 variants of concern including Omicron BA.4/5 and limited disease in Syrian hamsters. Collectively, these findings identify a class of IGHV1-46/IGKV3-20 antibodies that broadly neutralize betacoronaviruses by targeting the stem helix but indicate these antibodies constitute a small fraction of the broadly reactive antibody response to betacoronaviruses after SARS-CoV-2 infection.
Indexed as
COVID-19SARS-CoV-2AnimalsAntibodies, MonoclonalAntibodies, NeutralizingAntibodies, ViralCricetinaeDisease OutbreaksMesocricetusSpike Glycoprotein, CoronavirusAntibodies, MonoclonalAntibodies, NeutralizingAntibodies, ViralSpike Glycoprotein, Coronavirusspike protein, SARS-CoV-2betacoronavirusbroadly neutralizing antibodiesCOVID-19monoclonal antibodySARS-CoV-2stem helixvariants of concern
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