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Antigenic mapping reveals sites of vulnerability on α-HCoV spike protein

Understanding the antigenic signatures of all human coronaviruses (HCoVs) Spike (S) proteins is imperative for pan-HCoV epitopes identification and broadly effective vaccine development. To depict the currently elusive antigenic signatures of α-HCoVs S proteins, we isolated a panel of antibodies aga...

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Autores principales: Xiang, Jiangchao, Su, Jie, Lan, Qiaoshuai, Zhao, Wenwen, Zhou, Yu, Xu, Youwei, Niu, Jun, Xia, Shuai, Qi, Qilian, Sidhu, Sachdev, Lu, Lu, Miersch, Shane, Yang, Bei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9636267/
https://www.ncbi.nlm.nih.gov/pubmed/36333470
http://dx.doi.org/10.1038/s42003-022-04160-8
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author Xiang, Jiangchao
Su, Jie
Lan, Qiaoshuai
Zhao, Wenwen
Zhou, Yu
Xu, Youwei
Niu, Jun
Xia, Shuai
Qi, Qilian
Sidhu, Sachdev
Lu, Lu
Miersch, Shane
Yang, Bei
author_facet Xiang, Jiangchao
Su, Jie
Lan, Qiaoshuai
Zhao, Wenwen
Zhou, Yu
Xu, Youwei
Niu, Jun
Xia, Shuai
Qi, Qilian
Sidhu, Sachdev
Lu, Lu
Miersch, Shane
Yang, Bei
author_sort Xiang, Jiangchao
collection PubMed
description Understanding the antigenic signatures of all human coronaviruses (HCoVs) Spike (S) proteins is imperative for pan-HCoV epitopes identification and broadly effective vaccine development. To depict the currently elusive antigenic signatures of α-HCoVs S proteins, we isolated a panel of antibodies against the HCoV-229E S protein and characterized their epitopes and neutralizing potential. We found that the N-terminal domain of HCoV-229E S protein is antigenically dominant wherein an antigenic supersite is present and appears conserved in HCoV-NL63, which holds potential to serve as a pan-α-HCoVs epitope. In the receptor binding domain, a neutralizing epitope is captured in the end distal to the receptor binding site, reminiscent of the locations of the SARS-CoV-2 RBD cryptic epitopes. We also identified a neutralizing antibody that recognizes the connector domain, thus representing the first S2-directed neutralizing antibody against α-HCoVs. The unraveled HCoVs S proteins antigenic similarities and variances among genera highlight the challenges faced by pan-HCoV vaccine design while supporting the feasibility of broadly effective vaccine development against a subset of HCoVs.
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spelling pubmed-96362672022-11-06 Antigenic mapping reveals sites of vulnerability on α-HCoV spike protein Xiang, Jiangchao Su, Jie Lan, Qiaoshuai Zhao, Wenwen Zhou, Yu Xu, Youwei Niu, Jun Xia, Shuai Qi, Qilian Sidhu, Sachdev Lu, Lu Miersch, Shane Yang, Bei Commun Biol Article Understanding the antigenic signatures of all human coronaviruses (HCoVs) Spike (S) proteins is imperative for pan-HCoV epitopes identification and broadly effective vaccine development. To depict the currently elusive antigenic signatures of α-HCoVs S proteins, we isolated a panel of antibodies against the HCoV-229E S protein and characterized their epitopes and neutralizing potential. We found that the N-terminal domain of HCoV-229E S protein is antigenically dominant wherein an antigenic supersite is present and appears conserved in HCoV-NL63, which holds potential to serve as a pan-α-HCoVs epitope. In the receptor binding domain, a neutralizing epitope is captured in the end distal to the receptor binding site, reminiscent of the locations of the SARS-CoV-2 RBD cryptic epitopes. We also identified a neutralizing antibody that recognizes the connector domain, thus representing the first S2-directed neutralizing antibody against α-HCoVs. The unraveled HCoVs S proteins antigenic similarities and variances among genera highlight the challenges faced by pan-HCoV vaccine design while supporting the feasibility of broadly effective vaccine development against a subset of HCoVs. Nature Publishing Group UK 2022-11-04 /pmc/articles/PMC9636267/ /pubmed/36333470 http://dx.doi.org/10.1038/s42003-022-04160-8 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Xiang, Jiangchao
Su, Jie
Lan, Qiaoshuai
Zhao, Wenwen
Zhou, Yu
Xu, Youwei
Niu, Jun
Xia, Shuai
Qi, Qilian
Sidhu, Sachdev
Lu, Lu
Miersch, Shane
Yang, Bei
Antigenic mapping reveals sites of vulnerability on α-HCoV spike protein
title Antigenic mapping reveals sites of vulnerability on α-HCoV spike protein
title_full Antigenic mapping reveals sites of vulnerability on α-HCoV spike protein
title_fullStr Antigenic mapping reveals sites of vulnerability on α-HCoV spike protein
title_full_unstemmed Antigenic mapping reveals sites of vulnerability on α-HCoV spike protein
title_short Antigenic mapping reveals sites of vulnerability on α-HCoV spike protein
title_sort antigenic mapping reveals sites of vulnerability on α-hcov spike protein
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9636267/
https://www.ncbi.nlm.nih.gov/pubmed/36333470
http://dx.doi.org/10.1038/s42003-022-04160-8
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