The DOI matches its Crossref record; 90 of the 90 references it cites were found in a registry or an index.
N-terminal domain antigenic mapping reveals a site of vulnerability for SARS-CoV-2
Open accessPreprint — published as 10.1016/j.cell.2021.03.028 · Paper page
Abstract
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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“Neutralizing mAbs that bind regions of the viral spike have also been identified (24, 33, 38–42).”
From mRNA vaccination boosts cross-variant neutralizing antibodies elicited by SARS-CoV-2 infection (2021) · cites this paper as [39]
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“In older adults mean GMT was only 12 in a preliminary analysis of 12 participants19 and increased to 109 after the second dose.”
From Sensitivity of SARS-CoV-2 B.1.1.7 to mRNA vaccine-elicited antibodies (2021) · cites this paper as [19]
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BackgroundInfluential
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SARS-CoV-2 variants, spike mutations and immune escape
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Metadata
- Authors
- McCallum, M., Marco, A. D., Lempp, F., Tortorici, M. A., Pinto, D., Walls, A. C., Beltramello, M., Chen, A., Liu, Z., Zatta, F., Zepeda, S., di Iulio, J., Bowen, J. E., Montiel-Ruiz, M., Zhou, J., Rosen, L. E., Bianchi, S., Guarino, B., Fregni, C. S., Abdelnabi, R., Caroline Foo, S.-Y., Rothlauf, P. W., Bloyet, L.-M., Benigni, F., Cameroni, E., Neyts, J., Riva, A., Snell, G., Telenti, A., Whelan, S. P. J., Virgin, H. W., Corti, D., Pizzuto, M. S., & Veesler, D.
- Affiliations
- University of Washington (US)
- Vir Biotechnology (Switzerland) (CH)
- VIR Biotechnology (United States) (US)
- Centre National de la Recherche Scientifique (FR)
- Washington University in St. Louis (US)
- Rega Institute for Medical Research (BE)
- University of Milan (IT)
- Corresponding author
- Corti, Davide
- Pizzuto, Matteo Samuele
- Veesler, David
- ORCID
- McCallum, Matthew
- Marco, Anna De
- Lempp, Florian
- Tortorici, M. Alejandra
- Pinto, Dora
- Walls, Alexandra C.
- Beltramello, Martina
- Chen, Alex
- Liu, Zhuoming
- Zatta, Fabrizia
- Zepeda, Samantha
- Bowen, John E.
- Montiel-Ruiz, Martin
- Zhou, Jiayi
- Rosen, Laura E.
- Bianchi, Siro
- Guarino, Barbara
- Abdelnabi, Rana
- Rothlauf, Paul W.
- Bloyet, Louis-Marie
- Benigni, Fabio
- Cameroni, Elisabetta
- Neyts, Johan
- Riva, Agostino
- Snell, Gyorgy
- Telenti, Amalio
- Whelan, Sean P.J.
- Virgin, Herbert W.
- Corti, Davide
- Pizzuto, Matteo Samuele
- Veesler, David
- Venue
- Cell
- Publisher
- openRxiv
- Published
- 2021-01-14
- Volume
- 184
- Issue
- 9
- Pages
- 2332-2347.e16
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC7814825
- OpenAlex
- W3136616180
- Cited by
- 901
- References
- 0
- Citations by year
- 2026: 38 · 2025: 64 · 2024: 92 · 2023: 154 · 2022: 270 · 2021: 269
- FWCI
- 62.32
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cell (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Lirias (acceptedVersion, other-oa)
- PubMed Central (submittedVersion)
- HAL (submittedVersion)
- Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) (submittedVersion, other-oa)
- Lirias (submittedVersion, other-oa)
- Funders
- Burroughs Wellcome Fund
- University of Washington
- Fast Grants
- National Institutes of Health (1s10od023476-01)
- Natural Sciences and Engineering Research Council of Canada (HHSN272201700059C)
- National Institute of General Medical Sciences (R01GM120553, T32GM008268)
- National Institute of Allergy and Infectious Diseases (HHSN272201700059C, DP1AI158186)
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
- Keywords
- SARS-CoV-2, spike protein, N-terminal domain, neutralizing antibodies, monoclonal antibodies, antigenic mapping, receptor binding domain, SARS-CoV-2 variants, Alpha variant, Beta variant, P.1 lineage, vaccine design
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