Details

Autor(en) / Beteiligte

• Suryadevara, Naveenchandra
• Shrihari, Swathi
• Gilchuk, Pavlo
• VanBlargan, Laura A.
• Binshtein, Elad
• Zost, Seth J.
• Nargi, Rachel S.
• Sutton, Rachel E.
• Winkler, Emma S.
• Chen, Elaine C.
• Fouch, Mallorie E.
• Davidson, Edgar
• Doranz, Benjamin J.
• Chen, Rita E.
• Shi, Pei-Yong
• Carnahan, Robert H.
• Thackray, Larissa B.
• Diamond, Michael S.
• Crowe, James E.

Titel

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

Ist Teil von

• Cell, 2021-04, Vol.184 (9), p.2316-2331.e15

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2021

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. [Display omitted] •Natural SARS-2 infection induces a subset of potent N-terminal domain-specific mAbs•N-terminal domain reactive human monoclonal antibodies can neutralize live virus•COV2-2676 and COV2-2489 offer protection in a hACE2-transgenic mouse model•COV2-2676 and COV2-2489 Fc-effector functions are essential for optimal protection Suryadevara et al. find human neutralizing antibodies to the spike protein N-terminal domain that arise from natural infection with SARS-CoV-2. These antibodies inhibit post-attachment steps of the viral cycle and initiate protective immune responses via the antibody Fc domain.