Ultrapotent human antibodies protect against SARS-CoV-2 challenge via multiple mechanisms.

Autor: Tortorici MA; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.; Institut Pasteur and CNRS UMR 3569, Unité de Virologie Structurale, Paris, France., Beltramello M; Humabs BioMed SA, a subsidiary of Vir Biotechnology, Bellinzona, Switzerland., Lempp FA; Vir Biotechnology, San Francisco, CA 94158, USA., Pinto D; Humabs BioMed SA, a subsidiary of Vir Biotechnology, Bellinzona, Switzerland., Dang HV; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA., Rosen LE; Vir Biotechnology, San Francisco, CA 94158, USA., McCallum M; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA., Bowen J; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA., Minola A; Humabs BioMed SA, a subsidiary of Vir Biotechnology, Bellinzona, Switzerland., Jaconi S; Humabs BioMed SA, a subsidiary of Vir Biotechnology, Bellinzona, Switzerland., Zatta F; Humabs BioMed SA, a subsidiary of Vir Biotechnology, Bellinzona, Switzerland., De Marco A; Humabs BioMed SA, a subsidiary of Vir Biotechnology, Bellinzona, Switzerland., Guarino B; Humabs BioMed SA, a subsidiary of Vir Biotechnology, Bellinzona, Switzerland., Bianchi S; Humabs BioMed SA, a subsidiary of Vir Biotechnology, Bellinzona, Switzerland., Lauron EJ; Vir Biotechnology, San Francisco, CA 94158, USA., Tucker H; Vir Biotechnology, San Francisco, CA 94158, USA., Zhou J; Vir Biotechnology, San Francisco, CA 94158, USA., Peter A; Humabs BioMed SA, a subsidiary of Vir Biotechnology, Bellinzona, Switzerland., Havenar-Daughton C; Vir Biotechnology, San Francisco, CA 94158, USA., Wojcechowskyj JA; Vir Biotechnology, San Francisco, CA 94158, USA., Case JB; Departments of Medicine, Molecular Microbiology, Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA., Chen RE; Departments of Medicine, Molecular Microbiology, Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA., Kaiser H; Vir Biotechnology, San Francisco, CA 94158, USA., Montiel-Ruiz M; Vir Biotechnology, San Francisco, CA 94158, USA., Meury M; Vir Biotechnology, San Francisco, CA 94158, USA., Czudnochowski N; Vir Biotechnology, San Francisco, CA 94158, USA., Spreafico R; Vir Biotechnology, San Francisco, CA 94158, USA., Dillen J; Vir Biotechnology, San Francisco, CA 94158, USA., Ng C; Vir Biotechnology, San Francisco, CA 94158, USA., Sprugasci N; Humabs BioMed SA, a subsidiary of Vir Biotechnology, Bellinzona, Switzerland., Culap K; Humabs BioMed SA, a subsidiary of Vir Biotechnology, Bellinzona, Switzerland., Benigni F; Humabs BioMed SA, a subsidiary of Vir Biotechnology, Bellinzona, Switzerland., Abdelnabi R; Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, KU Leuven, Belgium., Foo SC; Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, KU Leuven, Belgium., Schmid MA; Humabs BioMed SA, a subsidiary of Vir Biotechnology, Bellinzona, Switzerland., Cameroni E; Humabs BioMed SA, a subsidiary of Vir Biotechnology, Bellinzona, Switzerland., Riva A; III Division of Infectious Diseases, Luigi Sacco University Hospital, University of Milan, Italy., Gabrieli A; III Division of Infectious Diseases, Luigi Sacco University Hospital, University of Milan, Italy., Galli M; III Division of Infectious Diseases, Luigi Sacco University Hospital, University of Milan, Italy., Pizzuto MS; Humabs BioMed SA, a subsidiary of Vir Biotechnology, Bellinzona, Switzerland., Neyts J; Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, KU Leuven, Belgium., Diamond MS; Departments of Medicine, Molecular Microbiology, Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA., Virgin HW; Vir Biotechnology, San Francisco, CA 94158, USA.; Washington University School of Medicine, St. Louis, MO, USA.; UTSouthwestern Medical Center, Dallas, TX, USA., Snell G; Vir Biotechnology, San Francisco, CA 94158, USA., Corti D; Humabs BioMed SA, a subsidiary of Vir Biotechnology, Bellinzona, Switzerland., Fink K; Humabs BioMed SA, a subsidiary of Vir Biotechnology, Bellinzona, Switzerland. dveesler@uw.edu katja.fink@alumni.ethz.ch., Veesler D; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA. dveesler@uw.edu katja.fink@alumni.ethz.ch.
Jazyk: angličtina
Zdroj: Science (New York, N.Y.) [Science] 2020 Nov 20; Vol. 370 (6519), pp. 950-957. Date of Electronic Publication: 2020 Sep 24.
DOI: 10.1126/science.abe3354
Abstrakt: Efficient therapeutic options are needed to control the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that has caused more than 922,000 fatalities as of 13 September 2020. We report the isolation and characterization of two ultrapotent SARS-CoV-2 human neutralizing antibodies (S2E12 and S2M11) that protect hamsters against SARS-CoV-2 challenge. Cryo-electron microscopy structures show that S2E12 and S2M11 competitively block angiotensin-converting enzyme 2 (ACE2) attachment and that S2M11 also locks the spike in a closed conformation by recognition of a quaternary epitope spanning two adjacent receptor-binding domains. Antibody cocktails that include S2M11, S2E12, or the previously identified S309 antibody broadly neutralize a panel of circulating SARS-CoV-2 isolates and activate effector functions. Our results pave the way to implement antibody cocktails for prophylaxis or therapy, circumventing or limiting the emergence of viral escape mutants.
(Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)
Databáze: MEDLINE
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