Neutralizing and protective human monoclonal antibodies recognizing the N-terminal domain of the SARS-CoV-2 spike protein.

BioRxiv : the Preprint Server for Biology
Naveenchandra SuryadevaraJames E Crowe

Abstract

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.

Citations

Mar 4, 2021·Nature Medicine·Constantinos Kurt WibmerPenny L Moore
Mar 17, 2021·Wiener klinische Wochenschrift·Franz X Heinz, Karin Stiasny
Mar 12, 2021·Nature·Dami A CollierRavindra K Gupta
Apr 22, 2021·MBio·Harini NatarajanMargaret E Ackerman

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Methods Mentioned

BETA
ELISA
electron microscopy
flow cytometry
transgenic
transfection

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