An Engineered Antibody with Broad Protective Efficacy in Murine Models of SARS and COVID-19.

Journal

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

Informations de publication

Date de publication:
17 Nov 2020
Historique:
pubmed: 26 11 2020
medline: 26 11 2020
entrez: 25 11 2020
Statut: epublish

Résumé

The recurrent zoonotic spillover of coronaviruses (CoVs) into the human population underscores the need for broadly active countermeasures. Here, we employed a directed evolution approach to engineer three SARS-CoV-2 antibodies for enhanced neutralization breadth and potency. One of the affinity-matured variants, ADG-2, displays strong binding activity to a large panel of sarbecovirus receptor binding domains (RBDs) and neutralizes representative epidemic sarbecoviruses with remarkable potency. Structural and biochemical studies demonstrate that ADG-2 employs a unique angle of approach to recognize a highly conserved epitope overlapping the receptor binding site. In murine models of SARS-CoV and SARS-CoV-2 infection, passive transfer of ADG-2 provided complete protection against respiratory burden, viral replication in the lungs, and lung pathology. Altogether, ADG-2 represents a promising broad-spectrum therapeutic candidate for the treatment and prevention of SARS-CoV-2 and future emerging SARS-like CoVs.

Identifiants

DOI: 10.1101/2020.11.17.385500 PMID: 33236009 PMC: PMC7685319
pubmed: 33236009
doi: 10.1101/2020.11.17.385500
pmc: PMC7685319
pii:
doi:

Types de publication

Preprint

Langues

eng

Subventions

Organisme : NIAID NIH HHS
ID : R01 AI132317
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI073148
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI132178
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI142777
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NCI NIH HHS
ID : U54 CA260543
Pays : United States

Déclaration de conflit d'intérêts

Competing interests: C.G.R, C.I.K, M.S., L.M.D., M.B.B., M.E.B., J.C.G., and L.M.W. are employees of Adimab, LLC and may hold shares in Adimab, LLC. L.M.W. is an employee of Adagio Therapeutics Inc. and holds shares in Adagio Therapeutics Inc. D.R.B. is on the SAB of Adimab, LLC and Adagio Therapeutics Inc. and holds shares in Adimab, LLC.

Auteurs

C Garrett Rappazzo (CG)

Adimab LLC, Lebanon, NH 03766, USA.

Longping V Tse (LV)

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

Chengzi I Kaku (CI)

Adimab LLC, Lebanon, NH 03766, USA.

Daniel Wrapp (D)

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

Mrunal Sakharkar (M)

Adimab LLC, Lebanon, NH 03766, USA.

Deli Huang (D)

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

Laura M Deveau (LM)

Adimab LLC, Lebanon, NH 03766, USA.

Thomas J Yockachonis (TJ)

Paul G. Allen School of Global Animal Health, Washington State University, Pullman, WA 99164, USA.

Andrew S Herbert (AS)

U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA.
The Geneva Foundation, 917 Pacific Avenue, Tacoma, WA 98402, USA.

Michael B Battles (MB)

Adimab LLC, Lebanon, NH 03766, USA.

Cecilia M O'Brien (CM)

U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA.
The Geneva Foundation, 917 Pacific Avenue, Tacoma, WA 98402, USA.

Michael E Brown (ME)

Adimab LLC, Lebanon, NH 03766, USA.

James C Geoghegan (JC)

Adimab LLC, Lebanon, NH 03766, USA.

Jonathan Belk (J)

Adimab LLC, Lebanon, NH 03766, USA.

Linghang Peng (L)

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

Linlin Yang (L)

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

Trevor D Scobey (TD)

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

Dennis R Burton (DR)

Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA.
Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard, Cambridge, MA 02139, USA.

David Nemazee (D)

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

John M Dye (JM)

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

James E Voss (JE)

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

Bronwyn M Gunn (BM)

Paul G. Allen School of Global Animal Health, Washington State University, Pullman, WA 99164, USA.

Jason S McLellan (JS)

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

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.

Lisa E Gralinski (LE)

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

Laura M Walker (LM)

Adimab LLC, Lebanon, NH 03766, USA.
Adagio Therapeutics, Inc., Waltham, MA 02451, USA.

Classifications MeSH