N-terminal domain antigenic mapping reveals a site of vulnerability for SARS-CoV-2
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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Preprint| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
bioRxiv.org - (2022) vom: 11. Dez. Zur Gesamtaufnahme - year:2022 |
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| Sprache: |
Englisch |
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| doi: |
10.1101/2021.01.14.426475 |
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| PPN (Katalog-ID): |
XBI019729790 |
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| 245 | 1 | 0 | |a N-terminal domain antigenic mapping reveals a site of vulnerability for SARS-CoV-2 |
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| 520 | |a 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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| 700 | 1 | |a Chen, Alex |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Zhuoming |e verfasserin |4 aut | |
| 700 | 1 | |a Zatta, Fabrizia |e verfasserin |4 aut | |
| 700 | 1 | |a Zepeda, Samantha |e verfasserin |4 aut | |
| 700 | 1 | |a di Iulio, Julia |e verfasserin |4 aut | |
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| 700 | 1 | |a Zhou, Jiayi |e verfasserin |4 aut | |
| 700 | 1 | |a Rosen, Laura E. |e verfasserin |4 aut | |
| 700 | 1 | |a Bianchi, Siro |e verfasserin |4 aut | |
| 700 | 1 | |a Guarino, Barbara |e verfasserin |4 aut | |
| 700 | 1 | |a Fregni, Chiara Silacci |e verfasserin |4 aut | |
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