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N-terminal domain antigenic mapping reveals a site of vulnerability for SARS-CoV-2.
McCallum, Matthew; De Marco, Anna; Lempp, Florian A; Tortorici, M Alejandra; Pinto, Dora; Walls, Alexandra C; Beltramello, Martina; Chen, Alex; Liu, Zhuoming; Zatta, Fabrizia; Zepeda, Samantha; di Iulio, Julia; Bowen, John E; Montiel-Ruiz, Martin; Zhou, Jiayi; Rosen, Laura E; Bianchi, Siro; Guarino, Barbara; Fregni, Chiara Silacci; Abdelnabi, Rana; Foo, Shi-Yan Caroline; Rothlauf, Paul W; Bloyet, Louis-Marie; Benigni, Fabio; Cameroni, Elisabetta; Neyts, Johan; Riva, Agostino; Snell, Gyorgy; Telenti, Amalio; Whelan, Sean P J; Virgin, Herbert W; Corti, Davide; Pizzuto, Matteo Samuele; Veesler, David.
  • McCallum M; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
  • De Marco A; Humabs Biomed SA, a subsidiary of Vir Biotechnology, 6500 Bellinzona, Switzerland.
  • Lempp FA; Vir Biotechnology, San Francisco, CA 94158, USA.
  • Tortorici MA; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA; Institut Pasteur and CNRS UMR 3569, Unité de Virologie Structurale, Paris, France.
  • Pinto D; Humabs Biomed SA, a subsidiary of Vir Biotechnology, 6500 Bellinzona, Switzerland.
  • Walls AC; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
  • Beltramello M; Humabs Biomed SA, a subsidiary of Vir Biotechnology, 6500 Bellinzona, Switzerland.
  • Chen A; Vir Biotechnology, San Francisco, CA 94158, USA.
  • Liu Z; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
  • Zatta F; Humabs Biomed SA, a subsidiary of Vir Biotechnology, 6500 Bellinzona, Switzerland.
  • Zepeda S; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
  • di Iulio J; Vir Biotechnology, San Francisco, CA 94158, USA.
  • Bowen JE; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
  • Montiel-Ruiz M; Vir Biotechnology, San Francisco, CA 94158, USA.
  • Zhou J; Vir Biotechnology, San Francisco, CA 94158, USA.
  • Rosen LE; Vir Biotechnology, San Francisco, CA 94158, USA.
  • Bianchi S; Humabs Biomed SA, a subsidiary of Vir Biotechnology, 6500 Bellinzona, Switzerland.
  • Guarino B; Humabs Biomed SA, a subsidiary of Vir Biotechnology, 6500 Bellinzona, Switzerland.
  • Fregni CS; Humabs Biomed SA, a subsidiary of Vir Biotechnology, 6500 Bellinzona, Switzerland.
  • Abdelnabi R; Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, 3000 Leuven, Belgium.
  • Foo SC; Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, 3000 Leuven, Belgium.
  • Rothlauf PW; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
  • Bloyet LM; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
  • Benigni F; Humabs Biomed SA, a subsidiary of Vir Biotechnology, 6500 Bellinzona, Switzerland.
  • Cameroni E; Humabs Biomed SA, a subsidiary of Vir Biotechnology, 6500 Bellinzona, Switzerland.
  • Neyts J; Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, 3000 Leuven, Belgium.
  • Riva A; III Division of Infectious Diseases, Luigi Sacco Hospital, University of Milan, 20157 Milan, Italy.
  • Snell G; Vir Biotechnology, San Francisco, CA 94158, USA.
  • Telenti A; Vir Biotechnology, San Francisco, CA 94158, USA.
  • Whelan SPJ; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
  • Virgin HW; Vir Biotechnology, San Francisco, CA 94158, USA.
  • Corti D; Humabs Biomed SA, a subsidiary of Vir Biotechnology, 6500 Bellinzona, Switzerland. Electronic address: dcorti@vir.bio.
  • Pizzuto MS; Humabs Biomed SA, a subsidiary of Vir Biotechnology, 6500 Bellinzona, Switzerland. Electronic address: mpizzuto@vir.bio.
  • Veesler D; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA. Electronic address: dveesler@uw.edu.
Cell ; 184(9): 2332-2347.e16, 2021 04 29.
Article in English | MEDLINE | ID: covidwho-1135276
Preprint
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ABSTRACT
The SARS-CoV-2 spike (S) glycoprotein contains an immunodominant receptor-binding domain (RBD) targeted by most 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 (designated site i) 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, albeit selecting escape mutants in some animals. Indeed, several SARS-CoV-2 variants, including the B.1.1.7, B.1.351, and P.1 lineages, harbor frequent mutations within the NTD supersite, suggesting ongoing selective pressure and the importance of NTD-specific neutralizing mAbs for protective immunity and vaccine design.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / Antigens, Viral Topics: Vaccines / Variants Limits: Animals Language: English Journal: Cell Year: 2021 Document Type: Article Affiliation country: J.cell.2021.03.028

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Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / Antigens, Viral Topics: Vaccines / Variants Limits: Animals Language: English Journal: Cell Year: 2021 Document Type: Article Affiliation country: J.cell.2021.03.028