Broad sarbecovirus neutralizing antibodies define a key site of vulnerability on the SARS-CoV-2 spike protein.

Journal

bioRxiv : the preprint server for biology
Titre abrégé: bioRxiv
Pays: United States
ID NLM: 101680187

Informations de publication

Date de publication:
16 May 2020
Historique:
pubmed: 9 6 2020
medline: 9 6 2020
entrez: 9 6 2020
Statut: epublish

Résumé

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.

Identifiants

DOI: 10.1101/2020.05.15.096511 PMID: 32511337 PMC: PMC7241100
pubmed: 32511337
doi: 10.1101/2020.05.15.096511
pmc: PMC7241100
pii:
doi:

Types de publication

Preprint

Langues

eng

Auteurs

Anna Z Wec (AZ)

Adimab LLC, Lebanon, NH 03766, USA.

Daniel Wrapp (D)

Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA.

Andrew S Herbert (AS)

U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA.

Daniel Maurer (D)

Adimab LLC, Lebanon, NH 03766, USA.

Denise Haslwanter (D)

Department of Microbiology and Immunology, Albert Einstein College of Medicine, New York, NY, USA.

Mrunal Sakharkar (M)

Adimab LLC, Lebanon, NH 03766, USA.

Rohit K Jangra (RK)

Department of Microbiology and Immunology, Albert Einstein College of Medicine, New York, NY, USA.

M Eugenia Dieterle (ME)

Department of Microbiology and Immunology, Albert Einstein College of Medicine, New York, NY, USA.

Asparouh Lilov (A)

Adimab LLC, Lebanon, NH 03766, USA.

Deli Huang (D)

Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.

Longping V Tse (LV)

Department of Epidemiology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

Nicole V Johnson (NV)

Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA.

Ching-Lin Hsieh (CL)

Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA.

Nianshuang Wang (N)

Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA.

Juergen H Nett (JH)

Adimab LLC, Lebanon, NH 03766, USA.

Elizabeth Champney (E)

Adimab LLC, Lebanon, NH 03766, USA.

Irina Burnina (I)

Adimab LLC, Lebanon, NH 03766, USA.

Michael Brown (M)

Adimab LLC, Lebanon, NH 03766, USA.

Shu Lin (S)

Adimab LLC, Lebanon, NH 03766, USA.

Melanie Sinclair (M)

Adimab LLC, Lebanon, NH 03766, USA.

Carl Johnson (C)

Adimab LLC, Lebanon, NH 03766, USA.

Sarat Pudi (S)

Adimab LLC, Lebanon, NH 03766, USA.

Robert Bortz (R)

Department of Microbiology and Immunology, Albert Einstein College of Medicine, New York, NY, USA.

Ariel S Wirchnianski (AS)

Department of Microbiology and Immunology, Albert Einstein College of Medicine, New York, NY, USA.

Ethan Laudermilch (E)

Department of Microbiology and Immunology, Albert Einstein College of Medicine, New York, NY, USA.

Catalina Florez (C)

Department of Microbiology and Immunology, Albert Einstein College of Medicine, New York, NY, USA.

J Maximilian Fels (JM)

Department of Microbiology and Immunology, Albert Einstein College of Medicine, New York, NY, USA.

Cecilia M O'Brien (CM)

U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA.

Barney S Graham (BS)

Adimab LLC, Lebanon, NH 03766, USA.
Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA.
U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA.
Department of Microbiology and Immunology, Albert Einstein College of Medicine, New York, NY, USA.
Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
Department of Epidemiology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
Consortium for HIV/AIDS Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA.
Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard.
Departments of Microbiology and Immunology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

David Nemazee (D)

Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.

Dennis R Burton (DR)

Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
Consortium for HIV/AIDS Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA.
Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard.

Ralph S Baric (RS)

Department of Epidemiology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Departments of Microbiology and Immunology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

James E Voss (JE)

Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.

Kartik Chandran (K)

Department of Microbiology and Immunology, Albert Einstein College of Medicine, New York, NY, USA.

John M Dye (JM)

U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA.

Jason S McLellan (JS)

Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA.

Laura M Walker (LM)

Adimab LLC, Lebanon, NH 03766, USA.

Classifications MeSH