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Structural and functional ramifications of antigenic drift in recent SARS-CoV-2 variants
The protective efficacy of neutralizing antibodies (nAbs) elicited during natural infection with SARS-CoV-2 and by vaccination based on its spike protein has been compromised with emergence of the recent SARS-CoV-2 variants. Residues E484 and K417 in the receptor-binding site (RBS) are both mutated...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7899451/ https://www.ncbi.nlm.nih.gov/pubmed/33619487 http://dx.doi.org/10.1101/2021.02.16.430500 |
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author | Yuan, Meng Huang, Deli Lee, Chang-Chun D. Wu, Nicholas C. Jackson, Abigail M. Zhu, Xueyong Liu, Hejun Peng, Linghang van Gils, Marit J. Sanders, Rogier W. Burton, Dennis R. Reincke, S. Momsen Prüss, Harald Kreye, Jakob Nemazee, David Ward, Andrew B. Wilson, Ian A. |
author_facet | Yuan, Meng Huang, Deli Lee, Chang-Chun D. Wu, Nicholas C. Jackson, Abigail M. Zhu, Xueyong Liu, Hejun Peng, Linghang van Gils, Marit J. Sanders, Rogier W. Burton, Dennis R. Reincke, S. Momsen Prüss, Harald Kreye, Jakob Nemazee, David Ward, Andrew B. Wilson, Ian A. |
author_sort | Yuan, Meng |
collection | PubMed |
description | The protective efficacy of neutralizing antibodies (nAbs) elicited during natural infection with SARS-CoV-2 and by vaccination based on its spike protein has been compromised with emergence of the recent SARS-CoV-2 variants. Residues E484 and K417 in the receptor-binding site (RBS) are both mutated in lineages first described in South Africa (B.1.351) and Brazil (B.1.1.28.1). The nAbs isolated from SARS-CoV-2 patients are preferentially encoded by certain heavy-chain germline genes and the two most frequently elicited antibody families (IGHV3–53/3–66 and IGHV1–2) can each bind the RBS in two different binding modes. However, their binding and neutralization are abrogated by either the E484K or K417N mutation, whereas nAbs to the cross-reactive CR3022 and S309 sites are largely unaffected. This structural and functional analysis illustrates why mutations at E484 and K417 adversely affect major classes of nAbs to SARS-CoV-2 with consequences for next-generation COVID-19 vaccines. |
format | Online Article Text |
id | pubmed-7899451 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Cold Spring Harbor Laboratory |
record_format | MEDLINE/PubMed |
spelling | pubmed-78994512021-02-23 Structural and functional ramifications of antigenic drift in recent SARS-CoV-2 variants Yuan, Meng Huang, Deli Lee, Chang-Chun D. Wu, Nicholas C. Jackson, Abigail M. Zhu, Xueyong Liu, Hejun Peng, Linghang van Gils, Marit J. Sanders, Rogier W. Burton, Dennis R. Reincke, S. Momsen Prüss, Harald Kreye, Jakob Nemazee, David Ward, Andrew B. Wilson, Ian A. bioRxiv Article The protective efficacy of neutralizing antibodies (nAbs) elicited during natural infection with SARS-CoV-2 and by vaccination based on its spike protein has been compromised with emergence of the recent SARS-CoV-2 variants. Residues E484 and K417 in the receptor-binding site (RBS) are both mutated in lineages first described in South Africa (B.1.351) and Brazil (B.1.1.28.1). The nAbs isolated from SARS-CoV-2 patients are preferentially encoded by certain heavy-chain germline genes and the two most frequently elicited antibody families (IGHV3–53/3–66 and IGHV1–2) can each bind the RBS in two different binding modes. However, their binding and neutralization are abrogated by either the E484K or K417N mutation, whereas nAbs to the cross-reactive CR3022 and S309 sites are largely unaffected. This structural and functional analysis illustrates why mutations at E484 and K417 adversely affect major classes of nAbs to SARS-CoV-2 with consequences for next-generation COVID-19 vaccines. Cold Spring Harbor Laboratory 2021-02-17 /pmc/articles/PMC7899451/ /pubmed/33619487 http://dx.doi.org/10.1101/2021.02.16.430500 Text en https://creativecommons.org/licenses/by-nc/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (https://creativecommons.org/licenses/by-nc/4.0/) , which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format for noncommercial purposes only, and only so long as attribution is given to the creator. |
spellingShingle | Article Yuan, Meng Huang, Deli Lee, Chang-Chun D. Wu, Nicholas C. Jackson, Abigail M. Zhu, Xueyong Liu, Hejun Peng, Linghang van Gils, Marit J. Sanders, Rogier W. Burton, Dennis R. Reincke, S. Momsen Prüss, Harald Kreye, Jakob Nemazee, David Ward, Andrew B. Wilson, Ian A. Structural and functional ramifications of antigenic drift in recent SARS-CoV-2 variants |
title | Structural and functional ramifications of antigenic drift in recent SARS-CoV-2 variants |
title_full | Structural and functional ramifications of antigenic drift in recent SARS-CoV-2 variants |
title_fullStr | Structural and functional ramifications of antigenic drift in recent SARS-CoV-2 variants |
title_full_unstemmed | Structural and functional ramifications of antigenic drift in recent SARS-CoV-2 variants |
title_short | Structural and functional ramifications of antigenic drift in recent SARS-CoV-2 variants |
title_sort | structural and functional ramifications of antigenic drift in recent sars-cov-2 variants |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7899451/ https://www.ncbi.nlm.nih.gov/pubmed/33619487 http://dx.doi.org/10.1101/2021.02.16.430500 |
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