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Broad sarbecovirus neutralizing antibodies define a key site of vulnerability on the SARS-CoV-2 spike protein.
Wec, Anna Z; Wrapp, Daniel; Herbert, Andrew S; Maurer, Daniel; Haslwanter, Denise; Sakharkar, Mrunal; Jangra, Rohit K; Dieterle, M Eugenia; Lilov, Asparouh; Huang, Deli; Tse, Longping V; Johnson, Nicole V; Hsieh, Ching-Lin; Wang, Nianshuang; Nett, Juergen H; Champney, Elizabeth; Burnina, Irina; Brown, Michael; Lin, Shu; Sinclair, Melanie; Johnson, Carl; Pudi, Sarat; Bortz, Robert; Wirchnianski, Ariel S; Laudermilch, Ethan; Florez, Catalina; Fels, J Maximilian; O'Brien, Cecilia M; Graham, Barney S; Nemazee, David; Burton, Dennis R; Baric, Ralph S; Voss, James E; Chandran, Kartik; Dye, John M; McLellan, Jason S; Walker, Laura M.
Afiliación
  • Wec AZ; Adimab LLC, Lebanon, NH 03766, USA.
  • Wrapp D; Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA.
  • Herbert AS; U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA.
  • Maurer D; Adimab LLC, Lebanon, NH 03766, USA.
  • Haslwanter D; Department of Microbiology and Immunology, Albert Einstein College of Medicine, New York, NY, USA.
  • Sakharkar M; Adimab LLC, Lebanon, NH 03766, USA.
  • Jangra RK; Department of Microbiology and Immunology, Albert Einstein College of Medicine, New York, NY, USA.
  • Dieterle ME; Department of Microbiology and Immunology, Albert Einstein College of Medicine, New York, NY, USA.
  • Lilov A; Adimab LLC, Lebanon, NH 03766, USA.
  • Huang D; Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Tse LV; Department of Epidemiology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  • Johnson NV; Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA.
  • Hsieh CL; Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA.
  • Wang N; Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA.
  • Nett JH; Adimab LLC, Lebanon, NH 03766, USA.
  • Champney E; Adimab LLC, Lebanon, NH 03766, USA.
  • Burnina I; Adimab LLC, Lebanon, NH 03766, USA.
  • Brown M; Adimab LLC, Lebanon, NH 03766, USA.
  • Lin S; Adimab LLC, Lebanon, NH 03766, USA.
  • Sinclair M; Adimab LLC, Lebanon, NH 03766, USA.
  • Johnson C; Adimab LLC, Lebanon, NH 03766, USA.
  • Pudi S; Adimab LLC, Lebanon, NH 03766, USA.
  • Bortz R; Department of Microbiology and Immunology, Albert Einstein College of Medicine, New York, NY, USA.
  • Wirchnianski AS; Department of Microbiology and Immunology, Albert Einstein College of Medicine, New York, NY, USA.
  • Laudermilch E; Department of Microbiology and Immunology, Albert Einstein College of Medicine, New York, NY, USA.
  • Florez C; Department of Microbiology and Immunology, Albert Einstein College of Medicine, New York, NY, USA.
  • Fels JM; Department of Microbiology and Immunology, Albert Einstein College of Medicine, New York, NY, USA.
  • O'Brien CM; U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA.
  • Graham BS; Adimab LLC, Lebanon, NH 03766, USA.
  • Nemazee D; Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA.
  • Burton DR; U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA.
  • Baric RS; Department of Microbiology and Immunology, Albert Einstein College of Medicine, New York, NY, USA.
  • Voss JE; Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Chandran K; Department of Epidemiology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  • Dye JM; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • McLellan JS; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Walker LM; Consortium for HIV/AIDS Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA.
bioRxiv ; 2020 May 16.
Article en En | MEDLINE | ID: mdl-32511337
ABSTRACT
Broadly protective vaccines against known and pre-emergent coronaviruses are urgently needed. Critical to their development is a deeper understanding of cross-neutralizing antibody responses induced by natural human coronavirus (HCoV) infections. Here, we mined the memory B cell repertoire of a convalescent SARS donor and identified 200 SARS-CoV-2 binding antibodies that target multiple conserved sites on the spike (S) protein. A large proportion of the antibodies display high levels of somatic hypermutation and cross-react with circulating HCoVs, suggesting recall of pre-existing memory B cells (MBCs) elicited by prior HCoV infections. Several antibodies potently cross-neutralize SARS-CoV, SARS-CoV-2, and the bat SARS-like virus WIV1 by blocking receptor attachment and inducing S1 shedding. These antibodies represent promising candidates for therapeutic intervention and reveal a new target for the rational design of pan-sarbecovirus vaccines.

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Idioma: En Revista: BioRxiv Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Idioma: En Revista: BioRxiv Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos