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Memory B cell repertoire from triple vaccinees against diverse SARS-CoV-2 variants
Omicron (B.1.1.529), the most heavily mutated SARS-CoV-2 variant so far, is highly resistant to neutralizing antibodies, raising concerns about the effectiveness of antibody therapies and vaccines(1,2). Here we examined whether sera from individuals who received two or three doses of inactivated SAR...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8967717/ https://www.ncbi.nlm.nih.gov/pubmed/35090164 http://dx.doi.org/10.1038/s41586-022-04466-x |
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author | Wang, Kang Jia, Zijing Bao, Linilin Wang, Lei Cao, Lei Chi, Hang Hu, Yaling Li, Qianqian Zhou, Yunjiao Jiang, Yinan Zhu, Qianhui Deng, Yongqiang Liu, Pan Wang, Nan Wang, Lin Liu, Min Li, Yurong Zhu, Boling Fan, Kaiyue Fu, Wangjun Yang, Peng Pei, Xinran Cui, Zhen Qin, Lili Ge, Pingju Wu, Jiajing Liu, Shuo Chen, Yiding Huang, Weijin Wang, Qiao Qin, Cheng-Feng Wang, Youchun Qin, Chuan Wang, Xiangxi |
author_facet | Wang, Kang Jia, Zijing Bao, Linilin Wang, Lei Cao, Lei Chi, Hang Hu, Yaling Li, Qianqian Zhou, Yunjiao Jiang, Yinan Zhu, Qianhui Deng, Yongqiang Liu, Pan Wang, Nan Wang, Lin Liu, Min Li, Yurong Zhu, Boling Fan, Kaiyue Fu, Wangjun Yang, Peng Pei, Xinran Cui, Zhen Qin, Lili Ge, Pingju Wu, Jiajing Liu, Shuo Chen, Yiding Huang, Weijin Wang, Qiao Qin, Cheng-Feng Wang, Youchun Qin, Chuan Wang, Xiangxi |
author_sort | Wang, Kang |
collection | PubMed |
description | Omicron (B.1.1.529), the most heavily mutated SARS-CoV-2 variant so far, is highly resistant to neutralizing antibodies, raising concerns about the effectiveness of antibody therapies and vaccines(1,2). Here we examined whether sera from individuals who received two or three doses of inactivated SARS-CoV-2 vaccine could neutralize authentic Omicron. The seroconversion rates of neutralizing antibodies were 3.3% (2 out of 60) and 95% (57 out of 60) for individuals who had received 2 and 3 doses of vaccine, respectively. For recipients of three vaccine doses, the geometric mean neutralization antibody titre for Omicron was 16.5-fold lower than for the ancestral virus (254). We isolated 323 human monoclonal antibodies derived from memory B cells in triple vaccinees, half of which recognized the receptor-binding domain, and showed that a subset (24 out of 163) potently neutralized all SARS-CoV-2 variants of concern, including Omicron. Therapeutic treatments with representative broadly neutralizing monoclonal antibodies were highly protective against infection of mice with SARS-CoV-2 Beta (B.1.351) and Omicron. Atomic structures of the Omicron spike protein in complex with three classes of antibodies that were active against all five variants of concern defined the binding and neutralizing determinants and revealed a key antibody escape site, G446S, that confers greater resistance to a class of antibodies that bind on the right shoulder of the receptor-binding domain by altering local conformation at the binding interface. Our results rationalize the use of three-dose immunization regimens and suggest that the fundamental epitopes revealed by these broadly ultrapotent antibodies are rational targets for a universal sarbecovirus vaccine. |
format | Online Article Text |
id | pubmed-8967717 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-89677172022-04-07 Memory B cell repertoire from triple vaccinees against diverse SARS-CoV-2 variants Wang, Kang Jia, Zijing Bao, Linilin Wang, Lei Cao, Lei Chi, Hang Hu, Yaling Li, Qianqian Zhou, Yunjiao Jiang, Yinan Zhu, Qianhui Deng, Yongqiang Liu, Pan Wang, Nan Wang, Lin Liu, Min Li, Yurong Zhu, Boling Fan, Kaiyue Fu, Wangjun Yang, Peng Pei, Xinran Cui, Zhen Qin, Lili Ge, Pingju Wu, Jiajing Liu, Shuo Chen, Yiding Huang, Weijin Wang, Qiao Qin, Cheng-Feng Wang, Youchun Qin, Chuan Wang, Xiangxi Nature Article Omicron (B.1.1.529), the most heavily mutated SARS-CoV-2 variant so far, is highly resistant to neutralizing antibodies, raising concerns about the effectiveness of antibody therapies and vaccines(1,2). Here we examined whether sera from individuals who received two or three doses of inactivated SARS-CoV-2 vaccine could neutralize authentic Omicron. The seroconversion rates of neutralizing antibodies were 3.3% (2 out of 60) and 95% (57 out of 60) for individuals who had received 2 and 3 doses of vaccine, respectively. For recipients of three vaccine doses, the geometric mean neutralization antibody titre for Omicron was 16.5-fold lower than for the ancestral virus (254). We isolated 323 human monoclonal antibodies derived from memory B cells in triple vaccinees, half of which recognized the receptor-binding domain, and showed that a subset (24 out of 163) potently neutralized all SARS-CoV-2 variants of concern, including Omicron. Therapeutic treatments with representative broadly neutralizing monoclonal antibodies were highly protective against infection of mice with SARS-CoV-2 Beta (B.1.351) and Omicron. Atomic structures of the Omicron spike protein in complex with three classes of antibodies that were active against all five variants of concern defined the binding and neutralizing determinants and revealed a key antibody escape site, G446S, that confers greater resistance to a class of antibodies that bind on the right shoulder of the receptor-binding domain by altering local conformation at the binding interface. Our results rationalize the use of three-dose immunization regimens and suggest that the fundamental epitopes revealed by these broadly ultrapotent antibodies are rational targets for a universal sarbecovirus vaccine. Nature Publishing Group UK 2022-01-28 2022 /pmc/articles/PMC8967717/ /pubmed/35090164 http://dx.doi.org/10.1038/s41586-022-04466-x 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 Wang, Kang Jia, Zijing Bao, Linilin Wang, Lei Cao, Lei Chi, Hang Hu, Yaling Li, Qianqian Zhou, Yunjiao Jiang, Yinan Zhu, Qianhui Deng, Yongqiang Liu, Pan Wang, Nan Wang, Lin Liu, Min Li, Yurong Zhu, Boling Fan, Kaiyue Fu, Wangjun Yang, Peng Pei, Xinran Cui, Zhen Qin, Lili Ge, Pingju Wu, Jiajing Liu, Shuo Chen, Yiding Huang, Weijin Wang, Qiao Qin, Cheng-Feng Wang, Youchun Qin, Chuan Wang, Xiangxi Memory B cell repertoire from triple vaccinees against diverse SARS-CoV-2 variants |
title | Memory B cell repertoire from triple vaccinees against diverse SARS-CoV-2 variants |
title_full | Memory B cell repertoire from triple vaccinees against diverse SARS-CoV-2 variants |
title_fullStr | Memory B cell repertoire from triple vaccinees against diverse SARS-CoV-2 variants |
title_full_unstemmed | Memory B cell repertoire from triple vaccinees against diverse SARS-CoV-2 variants |
title_short | Memory B cell repertoire from triple vaccinees against diverse SARS-CoV-2 variants |
title_sort | memory b cell repertoire from triple vaccinees against diverse sars-cov-2 variants |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8967717/ https://www.ncbi.nlm.nih.gov/pubmed/35090164 http://dx.doi.org/10.1038/s41586-022-04466-x |
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