N-terminal domain antigenic mapping reveals a site of vulnerability for SARS-CoV-2.
Cell
; 184(9): 2332-2347.e16, 2021 04 29.
Article
em En
| MEDLINE
| ID: mdl-33761326
ABSTRACT
The SARS-CoV-2 spike (S) glycoprotein contains an immunodominant receptor-binding domain (RBD) targeted by most neutralizing antibodies (Abs) in COVID-19 patient plasma. Little is known about neutralizing Abs binding to epitopes outside the RBD and their contribution to protection. Here, we describe 41 human monoclonal Abs (mAbs) derived from memory B cells, which recognize the SARS-CoV-2 S N-terminal domain (NTD) and show that a subset of them neutralize SARS-CoV-2 ultrapotently. We define an antigenic map of the SARS-CoV-2 NTD and identify a supersite (designated site i) recognized by all known NTD-specific neutralizing mAbs. These mAbs inhibit cell-to-cell fusion, activate effector functions, and protect Syrian hamsters from SARS-CoV-2 challenge, albeit selecting escape mutants in some animals. Indeed, several SARS-CoV-2 variants, including the B.1.1.7, B.1.351, and P.1 lineages, harbor frequent mutations within the NTD supersite, suggesting ongoing selective pressure and the importance of NTD-specific neutralizing mAbs for protective immunity and vaccine design.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
SARS-CoV-2
/
Antígenos Virais
Limite:
Animals
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article