N-terminal domain antigenic mapping reveals a site of vulnerability for SARS-CoV-2
Copyright policy )N-terminal domain antigenic mapping reveals a site of vulnerability for SARS-CoV-2
SARS-CoV-2 entry into host cells is orchestrated by the spike (S) glycoprotein that contains an immunodominant receptor-binding domain (RBD) targeted by the largest fraction of neutralizing antibodies (Abs) in COVID-19 patient plasma. Little is known about neutralizing Abs binding to epitopes outside the RBD and their contribution to protection. Here, we describe 41 human monoclonal Abs (mAbs) derived from memory B cells, which recognize the SARS-CoV-2 S N-terminal domain (NTD) and show that a subset of them neutralize SARS-CoV-2 ultrapotently. We define an antigenic map of the SARS-CoV-2 NTD and identify a supersite recognized by all known NTD-specific neutralizing mAbs. These mAbs inhibit cell-to-cell fusion, activate effector functions, and protect Syrian hamsters from SARS-CoV-2 challenge. SARS-CoV-2 variants, including the 501Y.V2 and B.1.1.7 lineages, harbor frequent mutations localized in the NTD supersite suggesting ongoing selective pressure and the importance of NTD-specific neutralizing mAbs to protective immunity.
- Washington University in St. Louis United States
- UNIVERSITY OF WASHINGTON
- University of Washington United States
- University of Washington, Department of Biochemistry United States
- Washington University in St. Louis United States
Models, Molecular, Biochemistry & Molecular Biology, N-terminal domain, PROTEIN, ACE2, CORONAVIRUS, VALIDATION, Article, STRUCTURAL DEFINITION, Protein Domains, NEUTRALIZING ANTIBODY, Neutralization Tests, Cricetinae, CRYO-EM STRUCTURE, memory B cells, Animals, Antigens, Viral, spike glycoprotein, 11 Medical and Health Sciences, Science & Technology, RECEPTOR-BINDING DOMAIN, MUTATIONS, SARS-CoV-2, 31 Biological sciences, neutralizing antibody, Antibodies, Monoclonal, COVID-19, Genetic Variation, MICROSCOPY, Cell Biology, 32 Biomedical and clinical sciences, 06 Biological Sciences, Antibodies, Neutralizing, NTD, COVID-19; memory B cells; N-terminal domain; neutralizing antibody; NTD; SARS-CoV-2; spike glycoprotein; Animals; Antibodies, Monoclonal; Antibodies, Neutralizing; Antigens, Viral; COVID-19; Cricetinae; Epitope Mapping; Genetic Variation; Models, Molecular; Mutation; Neutralization Tests; Protein Domains; RNA, Viral; SARS-CoV-2, Mutation, RNA, Viral, SPIKE GLYCOPROTEIN, Life Sciences & Biomedicine, Epitope Mapping, Developmental Biology
Models, Molecular, Biochemistry & Molecular Biology, N-terminal domain, PROTEIN, ACE2, CORONAVIRUS, VALIDATION, Article, STRUCTURAL DEFINITION, Protein Domains, NEUTRALIZING ANTIBODY, Neutralization Tests, Cricetinae, CRYO-EM STRUCTURE, memory B cells, Animals, Antigens, Viral, spike glycoprotein, 11 Medical and Health Sciences, Science & Technology, RECEPTOR-BINDING DOMAIN, MUTATIONS, SARS-CoV-2, 31 Biological sciences, neutralizing antibody, Antibodies, Monoclonal, COVID-19, Genetic Variation, MICROSCOPY, Cell Biology, 32 Biomedical and clinical sciences, 06 Biological Sciences, Antibodies, Neutralizing, NTD, COVID-19; memory B cells; N-terminal domain; neutralizing antibody; NTD; SARS-CoV-2; spike glycoprotein; Animals; Antibodies, Monoclonal; Antibodies, Neutralizing; Antigens, Viral; COVID-19; Cricetinae; Epitope Mapping; Genetic Variation; Models, Molecular; Mutation; Neutralization Tests; Protein Domains; RNA, Viral; SARS-CoV-2, Mutation, RNA, Viral, SPIKE GLYCOPROTEIN, Life Sciences & Biomedicine, Epitope Mapping, Developmental Biology
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