M. McCallum, A. De Marco, F. Lempp, M. Tortorici, D. Pinto, A. Walls, M. Beltramello, Alex Chen, Zhuoming Liu, F. Zatta, Samantha K. Zepeda, J. di Iulio, John E. Bowen, Martin Montiel-Ruiz, Jiayi Zhou, L. Rosen, S. Bianchi, B. Guarino, C. Fregni, R. Abdelnabi, S. Foo, P. W. Rothlauf, Louis-Marie Bloyet, F. Benigni, E. Cameroni, J. Neyts, A. Riva, G. Snell, A. Telenti, S. Whelan, H. Virgin, D. Corti, M. Pizzuto, D. Veesler
Cell, 2021
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 P1 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.
Cited by 48 publications.
Field of study: Medicine