tetano
Editor, Senior Moderator
Cell
. 2021 Mar 16;S0092-8674(21)00357-3.
doi: 10.1016/j.cell.2021.03.029. Online ahead of print.
Neutralizing and protective human monoclonal antibodies recognizing the N-terminal domain of the SARS-CoV-2 spike protein
Naveenchandra Suryadevara[SUP] 1 [/SUP], Swathi Shrihari[SUP] 2 [/SUP], Pavlo Gilchuk[SUP] 1 [/SUP], Laura A VanBlargan[SUP] 2 [/SUP], Elad Binshtein[SUP] 1 [/SUP], Seth J Zost[SUP] 1 [/SUP], Rachel S Nargi[SUP] 1 [/SUP], Rachel E Sutton[SUP] 1 [/SUP], Emma S Winkler[SUP] 3 [/SUP], Elaine C Chen[SUP] 4 [/SUP], Mallorie E Fouch[SUP] 5 [/SUP], Edgar Davidson[SUP] 5 [/SUP], Benjamin J Doranz[SUP] 5 [/SUP], Rita E Chen[SUP] 2 [/SUP], Pei-Yong Shi[SUP] 6 [/SUP], Robert H Carnahan[SUP] 7 [/SUP], Larissa B Thackray[SUP] 8 [/SUP], Michael S Diamond[SUP] 9 [/SUP], James E Crowe Jr[SUP] 10 [/SUP]
Affiliations
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.
Keywords: N-terminal domain; SARS-CoV-2; coronavirus; monoclonal antibodies; neutralizing antibodies; viral antibodies.
. 2021 Mar 16;S0092-8674(21)00357-3.
doi: 10.1016/j.cell.2021.03.029. Online ahead of print.
Neutralizing and protective human monoclonal antibodies recognizing the N-terminal domain of the SARS-CoV-2 spike protein
Naveenchandra Suryadevara[SUP] 1 [/SUP], Swathi Shrihari[SUP] 2 [/SUP], Pavlo Gilchuk[SUP] 1 [/SUP], Laura A VanBlargan[SUP] 2 [/SUP], Elad Binshtein[SUP] 1 [/SUP], Seth J Zost[SUP] 1 [/SUP], Rachel S Nargi[SUP] 1 [/SUP], Rachel E Sutton[SUP] 1 [/SUP], Emma S Winkler[SUP] 3 [/SUP], Elaine C Chen[SUP] 4 [/SUP], Mallorie E Fouch[SUP] 5 [/SUP], Edgar Davidson[SUP] 5 [/SUP], Benjamin J Doranz[SUP] 5 [/SUP], Rita E Chen[SUP] 2 [/SUP], Pei-Yong Shi[SUP] 6 [/SUP], Robert H Carnahan[SUP] 7 [/SUP], Larissa B Thackray[SUP] 8 [/SUP], Michael S Diamond[SUP] 9 [/SUP], James E Crowe Jr[SUP] 10 [/SUP]
Affiliations
- PMID: 33773105
- DOI: 10.1016/j.cell.2021.03.029
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.
Keywords: N-terminal domain; SARS-CoV-2; coronavirus; monoclonal antibodies; neutralizing antibodies; viral antibodies.