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.

N-terminal domain antigenic mapping reveals a site of vulnerability for SARS-CoV-2 / M. McCallum, A. De Marco, F.A. Lempp, M.A. Tortorici, D. Pinto, A.C. Walls, M. Beltramello, A. Chen, Z. Liu, F. Zatta, S. Zepeda, J. di Iulio, J.E. Bowen, M. Montiel-Ruiz, J. Zhou, L.E. Rosen, S. Bianchi, B. Guarino, C.S. Fregni, R. Abdelnabi, S.-.C. Foo, P.W. Rothlauf, L.-. Bloyet, F. Benigni, E. Cameroni, J. Neyts, A. Riva, G. Snell, A. Telenti, S.P.J. Whelan, H.W. Virgin, D. Corti, M.S. Pizzuto, D. Veesler. - In: CELL. - ISSN 0092-8674. - 184:9(2021), pp. 2332-2347. [10.1016/j.cell.2021.03.028]

N-terminal domain antigenic mapping reveals a site of vulnerability for SARS-CoV-2

A. Riva;
2021

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.
COVID-19; memory B cells; N-terminal domain; neutralizing antibody; NTD; SARS-CoV-2; spike glycoprotein; Animals; Antibodies, Monoclonal; Antibodies, Neutralizing; Antigens, Viral; COVID-19; Cricetinae; Epitope Mapping; Genetic Variation; Models, Molecular; Mutation; Neutralization Tests; Protein Domains; RNA, Viral; SARS-CoV-2
Settore MED/17 - Malattie Infettive
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/861701
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