N-terminal domain antigenic mapping reveals a site of vulnerability for SARS-CoV-2
Matthew McCallum; Anna De Marco; Florian Lempp; M. Alejandra Tortorici; Dora Pinto; Alexandra C Walls; Martina Beltramello; Alex Chen; Zhuoming Liu; Fabrizia Zatta; Samantha Zepeda; Julia di Iulio; John E Bowen; Martin Montiel-Ruiz; Jiayi Zhou; Laura Rosen; Siro Bianchi; Barbara Guarino; Chiara Silacci Fregni; Rana Abdelnabi; Shi-Yan Caroline Foo; Paul W Rothlauf; Louis-Marie Bloyet; Fabio Benigni; Elisabetta Cameroni; Johan Neyts; Agostino Riva; Gyorgy Snell; Amalio Telenti; Sean PJ Whelan; Herbert W Virgin; Davide Corti; Matteo Samuele Pizzuto; David Veesler.
Preprint
en Inglés
| PREPRINT-BIORXIV | ID: ppbiorxiv-426475
SARS-CoV-2 entry into host cells is orchestrated by the spike (S) glycoprotein that contains an immunodominant receptor-binding domain (RBD) targeted by the largest fraction of 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 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. SARS-CoV-2 variants, including the 501Y.V2 and B.1.1.7 lineages, harbor frequent mutations localized in the NTD supersite suggesting ongoing selective pressure and the importance of NTD-specific neutralizing mAbs to protective immunity.
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