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.
| File | Dimensione | Formato | |
|---|---|---|---|
|
1-s2.0-S0092867421003561-main.pdf
accesso aperto
Tipologia:
Publisher's version/PDF
Dimensione
9.39 MB
Formato
Adobe PDF
|
9.39 MB | Adobe PDF | Visualizza/Apri |
Pubblicazioni consigliate
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
