RT Journal Article
SR Electronic
T1 Neutralizing and protective human monoclonal antibodies recognizing the N-terminal domain of the SARS-CoV-2 spike protein
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.01.19.427324
DO 10.1101/2021.01.19.427324
A1 Suryadevara, Naveenchandra
A1 Shrihari, Swathi
A1 Gilchuk, Pavlo
A1 VanBlargan, Laura A.
A1 Binshtein, Elad
A1 Zost, Seth J.
A1 Nargi, Rachel S.
A1 Sutton, Rachel E.
A1 Winkler, Emma S.
A1 Chen, Elaine C.
A1 Fouch, Mallorie E.
A1 Davidson, Edgar
A1 Doranz, Benjamin J.
A1 Carnahan, Robert H.
A1 Thackray, Larissa B.
A1 Diamond, Michael S.
A1 Crowe, James E.
YR 2021
UL http://biorxiv.org/content/early/2021/01/20/2021.01.19.427324.abstract
AB Most human monoclonal antibodies (mAbs) neutralizing SARS-CoV-2 recognize the spike (S) protein receptor-binding domain and block virus interactions with the cellular receptor angiotensin-converting enzyme 2. We describe a panel of human mAbs binding to diverse epitopes on the N-terminal domain (NTD) of S protein from SARS-CoV-2 convalescent donors and found a minority of these possessed neutralizing activity. Two mAbs (COV2-2676 and COV2-2489) inhibited infection of authentic SARS-CoV-2 and recombinant VSV/SARS-CoV-2 viruses. We mapped their binding epitopes by alanine-scanning mutagenesis and selection of functional SARS-CoV-2 S neutralization escape variants. Mechanistic studies showed that these antibodies neutralize in part by inhibiting a post-attachment step in the infection cycle. COV2-2676 and COV2-2489 offered protection either as prophylaxis or therapy, and Fc effector functions were required for optimal protection. Thus, natural infection induces a subset of potent NTD-specific mAbs that leverage neutralizing and Fc-mediated activities to protect against SARS-CoV-2 infection using multiple functional attributes.Competing Interest StatementM.E.F., E.D., and B.J.D. are employees of Integral Molecular. B.J.D. is a shareholder of Integral Molecular. M.S.D. is a consultant for Inbios, Vir Biotechnology, NGM Biopharmaceuticals, and Carnival Corporation, is on the Scientific Advisory Boards of Moderna and Immunome, and the Diamond laboratory at Washington University School of Medicine has received sponsored research agreements from Emergent BioSolutions, Moderna, and Vir Biotechnology. J.E.C. has served as a consultant for Eli Lilly, GlaxoSmithKline and Luna Biologics, is a member of the Scientific Advisory Boards of CompuVax and Meissa Vaccines and is Founder of IDBiologics. The Crowe laboratory at Vanderbilt University Medical Center has received unrelated sponsored research agreements from IDBiologics and AstraZeneca.