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Ultrapotent human antibodies protect against SARS-CoV-2 challenge via multiple mechanisms.
Tortorici, M Alejandra; Beltramello, Martina; Lempp, Florian A; Pinto, Dora; Dang, Ha V; Rosen, Laura E; McCallum, Matthew; Bowen, John; Minola, Andrea; Jaconi, Stefano; Zatta, Fabrizia; De Marco, Anna; Guarino, Barbara; Bianchi, Siro; Lauron, Elvin J; Tucker, Heather; Zhou, Jiayi; Peter, Alessia; Havenar-Daughton, Colin; Wojcechowskyj, Jason A; Case, James Brett; Chen, Rita E; Kaiser, Hannah; Montiel-Ruiz, Martin; Meury, Marcel; Czudnochowski, Nadine; Spreafico, Roberto; Dillen, Josh; Ng, Cindy; Sprugasci, Nicole; Culap, Katja; Benigni, Fabio; Abdelnabi, Rana; Foo, Shi-Yan Caroline; Schmid, Michael A; Cameroni, Elisabetta; Riva, Agostino; Gabrieli, Arianna; Galli, Massimo; Pizzuto, Matteo S; Neyts, Johan; Diamond, Michael S; Virgin, Herbert W; Snell, Gyorgy; Corti, Davide; Fink, Katja; Veesler, David.
Afiliación
  • Tortorici MA; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
  • Beltramello M; Institut Pasteur and CNRS UMR 3569, Unité de Virologie Structurale, Paris, France.
  • Lempp FA; Humabs BioMed SA, a subsidiary of Vir Biotechnology, Bellinzona, Switzerland.
  • Pinto D; Vir Biotechnology, San Francisco, CA 94158, USA.
  • Dang HV; Humabs BioMed SA, a subsidiary of Vir Biotechnology, Bellinzona, Switzerland.
  • Rosen LE; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
  • McCallum M; Vir Biotechnology, San Francisco, CA 94158, USA.
  • Bowen J; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
  • Minola A; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
  • 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; Humabs BioMed SA, a subsidiary of Vir Biotechnology, Bellinzona, Switzerland.
  • Tucker H; Vir Biotechnology, San Francisco, CA 94158, USA.
  • Zhou J; Vir Biotechnology, San Francisco, CA 94158, USA.
  • Peter A; Vir Biotechnology, San Francisco, CA 94158, USA.
  • Havenar-Daughton C; Humabs BioMed SA, a subsidiary of Vir Biotechnology, Bellinzona, Switzerland.
  • Wojcechowskyj JA; Vir Biotechnology, San Francisco, CA 94158, USA.
  • Case JB; Vir Biotechnology, San Francisco, CA 94158, USA.
  • Chen RE; Departments of Medicine, Molecular Microbiology, Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.
  • Kaiser H; Departments of Medicine, Molecular Microbiology, Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, 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; Vir Biotechnology, San Francisco, CA 94158, USA.
  • 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; Humabs BioMed SA, a subsidiary of Vir Biotechnology, Bellinzona, Switzerland.
  • Foo SC; Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, KU Leuven, Belgium.
  • Schmid MA; Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, KU Leuven, Belgium.
  • Cameroni E; Humabs BioMed SA, a subsidiary of Vir Biotechnology, Bellinzona, Switzerland.
  • Riva A; Humabs BioMed SA, a subsidiary of Vir Biotechnology, Bellinzona, Switzerland.
  • 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; III Division of Infectious Diseases, Luigi Sacco University Hospital, University of Milan, Italy.
  • Neyts J; Humabs BioMed SA, a subsidiary of Vir Biotechnology, Bellinzona, Switzerland.
  • Diamond MS; Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, KU Leuven, Belgium.
  • Virgin HW; Departments of Medicine, Molecular Microbiology, Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.
  • Snell G; Vir Biotechnology, San Francisco, CA 94158, USA.
  • Corti D; Washington University School of Medicine, St. Louis, MO, USA.
  • Fink K; UTSouthwestern Medical Center, Dallas, TX, USA.
  • Veesler D; Vir Biotechnology, San Francisco, CA 94158, USA.
Science ; 370(6519): 950-957, 2020 11 20.
Article en En | MEDLINE | ID: mdl-32972994
ABSTRACT
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.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Neumonía Viral / Infecciones por Coronavirus / Peptidil-Dipeptidasa A / Anticuerpos Neutralizantes / Pandemias / Glicoproteína de la Espiga del Coronavirus / Betacoronavirus / Anticuerpos Antivirales Límite: Animals / Humans Idioma: En Revista: Science Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Neumonía Viral / Infecciones por Coronavirus / Peptidil-Dipeptidasa A / Anticuerpos Neutralizantes / Pandemias / Glicoproteína de la Espiga del Coronavirus / Betacoronavirus / Anticuerpos Antivirales Límite: Animals / Humans Idioma: En Revista: Science Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos