Potent and broadly neutralizing antibodies against sarbecoviruses induced by sequential COVID-19 vaccination
Abstract The current SARS-CoV-2 variants strikingly evade all authorized monoclonal antibodies and threaten the efficacy of serum-neutralizing activity elicited by vaccination or prior infection, urging the need to develop antivirals against SARS-CoV-2 and related sarbecoviruses. Here, we identified...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2024-02-01
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| Series: | Cell Discovery |
| Online Access: | https://doi.org/10.1038/s41421-024-00648-1 |
| _version_ | 1797275926921216000 |
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| author | Xiaoyu Zhao Tianyi Qiu Xiner Huang Qiyu Mao Yajie Wang Rui Qiao Jiayan Li Tiantian Mao Yuan Wang Yewei Cun Caicui Wang Cuiting Luo Chaemin Yoon Xun Wang Chen Li Yuchen Cui Chaoyue Zhao Minghui Li Yanjia Chen Guonan Cai Wenye Geng Zixin Hu Jinglei Cao Wenhong Zhang Zhiwei Cao Hin Chu Lei Sun Pengfei Wang |
| author_facet | Xiaoyu Zhao Tianyi Qiu Xiner Huang Qiyu Mao Yajie Wang Rui Qiao Jiayan Li Tiantian Mao Yuan Wang Yewei Cun Caicui Wang Cuiting Luo Chaemin Yoon Xun Wang Chen Li Yuchen Cui Chaoyue Zhao Minghui Li Yanjia Chen Guonan Cai Wenye Geng Zixin Hu Jinglei Cao Wenhong Zhang Zhiwei Cao Hin Chu Lei Sun Pengfei Wang |
| author_sort | Xiaoyu Zhao |
| collection | DOAJ |
| description | Abstract The current SARS-CoV-2 variants strikingly evade all authorized monoclonal antibodies and threaten the efficacy of serum-neutralizing activity elicited by vaccination or prior infection, urging the need to develop antivirals against SARS-CoV-2 and related sarbecoviruses. Here, we identified both potent and broadly neutralizing antibodies from a five-dose vaccinated donor who exhibited cross-reactive serum-neutralizing activity against diverse coronaviruses. Through single B-cell sorting and sequencing followed by a tailor-made computational pipeline, we successfully selected 86 antibodies with potential cross-neutralizing ability from 684 antibody sequences. Among them, PW5-570 potently neutralized all SARS-CoV-2 variants that arose prior to Omicron BA.5, and the other three could broadly neutralize all current SARS-CoV-2 variants of concern, SARS-CoV and their related sarbecoviruses (Pangolin-GD, RaTG13, WIV-1, and SHC014). Cryo-EM analysis demonstrates that these antibodies have diverse neutralization mechanisms, such as disassembling spike trimers, or binding to RBM or SD1 to affect ACE2 binding. In addition, prophylactic administration of these antibodies significantly protects nasal turbinate and lung infections against BA.1, XBB.1, and SARS-CoV viral challenge in golden Syrian hamsters, respectively. Importantly, post-exposure treatment with PW5-5 and PW5-535 also markedly protects against XBB.1 challenge in these models. This study reveals the potential utility of computational process to assist screening cross-reactive antibodies, as well as the potency of vaccine-induced broadly neutralizing antibodies against current SARS-CoV-2 variants and related sarbecoviruses, offering promising avenues for the development of broad therapeutic antibody drugs. |
| first_indexed | 2024-03-07T15:21:03Z |
| format | Article |
| id | doaj.art-84a0d3471e3148dd8c77e8ac94e5c60d |
| institution | Directory Open Access Journal |
| issn | 2056-5968 |
| language | English |
| last_indexed | 2024-03-07T15:21:03Z |
| publishDate | 2024-02-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Discovery |
| spelling | doaj.art-84a0d3471e3148dd8c77e8ac94e5c60d2024-03-05T17:40:08ZengNature Publishing GroupCell Discovery2056-59682024-02-0110112110.1038/s41421-024-00648-1Potent and broadly neutralizing antibodies against sarbecoviruses induced by sequential COVID-19 vaccinationXiaoyu Zhao0Tianyi Qiu1Xiner Huang2Qiyu Mao3Yajie Wang4Rui Qiao5Jiayan Li6Tiantian Mao7Yuan Wang8Yewei Cun9Caicui Wang10Cuiting Luo11Chaemin Yoon12Xun Wang13Chen Li14Yuchen Cui15Chaoyue Zhao16Minghui Li17Yanjia Chen18Guonan Cai19Wenye Geng20Zixin Hu21Jinglei Cao22Wenhong Zhang23Zhiwei Cao24Hin Chu25Lei Sun26Pengfei Wang27Shanghai Pudong Hospital, Fudan University Pudong Medical Center, State Key Laboratory of Genetic Engineering, MOE Engineering Research Center of Gene Technology, School of Life Sciences, Shanghai Institute of Infectious Disease and Biosecurity, Institutes of Biomedical Sciences, Shanghai Sci-Tech Inno Center for Infection & Immunity, Fudan UniversityInstitute of Clinical Science, ZhongShan Hospital, Shanghai Institute of Infectious Disease and Biosecurity, Fudan UniversityDepartment of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong KongShanghai Pudong Hospital, Fudan University Pudong Medical Center, State Key Laboratory of Genetic Engineering, MOE Engineering Research Center of Gene Technology, School of Life Sciences, Shanghai Institute of Infectious Disease and Biosecurity, Institutes of Biomedical Sciences, Shanghai Sci-Tech Inno Center for Infection & Immunity, Fudan UniversityShanghai Pudong Hospital, Fudan University Pudong Medical Center, State Key Laboratory of Genetic Engineering, MOE Engineering Research Center of Gene Technology, School of Life Sciences, Shanghai Institute of Infectious Disease and Biosecurity, Institutes of Biomedical Sciences, Shanghai Sci-Tech Inno Center for Infection & Immunity, Fudan UniversityShanghai Pudong Hospital, Fudan University Pudong Medical Center, State Key Laboratory of Genetic Engineering, MOE Engineering Research Center of Gene Technology, School of Life Sciences, Shanghai Institute of Infectious Disease and Biosecurity, Institutes of Biomedical Sciences, Shanghai Sci-Tech Inno Center for Infection & Immunity, Fudan UniversityShanghai Pudong Hospital, Fudan University Pudong Medical Center, State Key Laboratory of Genetic Engineering, MOE Engineering Research Center of Gene Technology, School of Life Sciences, Shanghai Institute of Infectious Disease and Biosecurity, Institutes of Biomedical Sciences, Shanghai Sci-Tech Inno Center for Infection & Immunity, Fudan UniversitySchool of Life Sciences, Fudan UniversitySchool of Life Sciences and Technology, Tongji UniversitySchool of Life Sciences, Fudan UniversitySchool of Life Sciences and Technology, Tongji UniversityDepartment of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong KongDepartment of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong KongShanghai Pudong Hospital, Fudan University Pudong Medical Center, State Key Laboratory of Genetic Engineering, MOE Engineering Research Center of Gene Technology, School of Life Sciences, Shanghai Institute of Infectious Disease and Biosecurity, Institutes of Biomedical Sciences, Shanghai Sci-Tech Inno Center for Infection & Immunity, Fudan UniversityShanghai Pudong Hospital, Fudan University Pudong Medical Center, State Key Laboratory of Genetic Engineering, MOE Engineering Research Center of Gene Technology, School of Life Sciences, Shanghai Institute of Infectious Disease and Biosecurity, Institutes of Biomedical Sciences, Shanghai Sci-Tech Inno Center for Infection & Immunity, Fudan UniversityShanghai Pudong Hospital, Fudan University Pudong Medical Center, State Key Laboratory of Genetic Engineering, MOE Engineering Research Center of Gene Technology, School of Life Sciences, Shanghai Institute of Infectious Disease and Biosecurity, Institutes of Biomedical Sciences, Shanghai Sci-Tech Inno Center for Infection & Immunity, Fudan UniversityShanghai Pudong Hospital, Fudan University Pudong Medical Center, State Key Laboratory of Genetic Engineering, MOE Engineering Research Center of Gene Technology, School of Life Sciences, Shanghai Institute of Infectious Disease and Biosecurity, Institutes of Biomedical Sciences, Shanghai Sci-Tech Inno Center for Infection & Immunity, Fudan UniversityShanghai Pudong Hospital, Fudan University Pudong Medical Center, State Key Laboratory of Genetic Engineering, MOE Engineering Research Center of Gene Technology, School of Life Sciences, Shanghai Institute of Infectious Disease and Biosecurity, Institutes of Biomedical Sciences, Shanghai Sci-Tech Inno Center for Infection & Immunity, Fudan UniversityShanghai Pudong Hospital, Fudan University Pudong Medical Center, State Key Laboratory of Genetic Engineering, MOE Engineering Research Center of Gene Technology, School of Life Sciences, Shanghai Institute of Infectious Disease and Biosecurity, Institutes of Biomedical Sciences, Shanghai Sci-Tech Inno Center for Infection & Immunity, Fudan UniversityShanghai Pudong Hospital, Fudan University Pudong Medical Center, State Key Laboratory of Genetic Engineering, MOE Engineering Research Center of Gene Technology, School of Life Sciences, Shanghai Institute of Infectious Disease and Biosecurity, Institutes of Biomedical Sciences, Shanghai Sci-Tech Inno Center for Infection & Immunity, Fudan UniversityFudan Zhangjiang Institute, Shanghai Medical College of Fudan University, Fudan UniversityShanghai Pudong Hospital, Fudan University Pudong Medical Center, State Key Laboratory of Genetic Engineering, MOE Engineering Research Center of Gene Technology, School of Life Sciences, Shanghai Institute of Infectious Disease and Biosecurity, Institutes of Biomedical Sciences, Shanghai Sci-Tech Inno Center for Infection & Immunity, Fudan UniversityDepartment of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan UniversityDepartment of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan UniversitySchool of Life Sciences, Fudan UniversityDepartment of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong KongShanghai Pudong Hospital, Fudan University Pudong Medical Center, State Key Laboratory of Genetic Engineering, MOE Engineering Research Center of Gene Technology, School of Life Sciences, Shanghai Institute of Infectious Disease and Biosecurity, Institutes of Biomedical Sciences, Shanghai Sci-Tech Inno Center for Infection & Immunity, Fudan UniversityShanghai Pudong Hospital, Fudan University Pudong Medical Center, State Key Laboratory of Genetic Engineering, MOE Engineering Research Center of Gene Technology, School of Life Sciences, Shanghai Institute of Infectious Disease and Biosecurity, Institutes of Biomedical Sciences, Shanghai Sci-Tech Inno Center for Infection & Immunity, Fudan UniversityAbstract The current SARS-CoV-2 variants strikingly evade all authorized monoclonal antibodies and threaten the efficacy of serum-neutralizing activity elicited by vaccination or prior infection, urging the need to develop antivirals against SARS-CoV-2 and related sarbecoviruses. Here, we identified both potent and broadly neutralizing antibodies from a five-dose vaccinated donor who exhibited cross-reactive serum-neutralizing activity against diverse coronaviruses. Through single B-cell sorting and sequencing followed by a tailor-made computational pipeline, we successfully selected 86 antibodies with potential cross-neutralizing ability from 684 antibody sequences. Among them, PW5-570 potently neutralized all SARS-CoV-2 variants that arose prior to Omicron BA.5, and the other three could broadly neutralize all current SARS-CoV-2 variants of concern, SARS-CoV and their related sarbecoviruses (Pangolin-GD, RaTG13, WIV-1, and SHC014). Cryo-EM analysis demonstrates that these antibodies have diverse neutralization mechanisms, such as disassembling spike trimers, or binding to RBM or SD1 to affect ACE2 binding. In addition, prophylactic administration of these antibodies significantly protects nasal turbinate and lung infections against BA.1, XBB.1, and SARS-CoV viral challenge in golden Syrian hamsters, respectively. Importantly, post-exposure treatment with PW5-5 and PW5-535 also markedly protects against XBB.1 challenge in these models. This study reveals the potential utility of computational process to assist screening cross-reactive antibodies, as well as the potency of vaccine-induced broadly neutralizing antibodies against current SARS-CoV-2 variants and related sarbecoviruses, offering promising avenues for the development of broad therapeutic antibody drugs.https://doi.org/10.1038/s41421-024-00648-1 |
| spellingShingle | Xiaoyu Zhao Tianyi Qiu Xiner Huang Qiyu Mao Yajie Wang Rui Qiao Jiayan Li Tiantian Mao Yuan Wang Yewei Cun Caicui Wang Cuiting Luo Chaemin Yoon Xun Wang Chen Li Yuchen Cui Chaoyue Zhao Minghui Li Yanjia Chen Guonan Cai Wenye Geng Zixin Hu Jinglei Cao Wenhong Zhang Zhiwei Cao Hin Chu Lei Sun Pengfei Wang Potent and broadly neutralizing antibodies against sarbecoviruses induced by sequential COVID-19 vaccination Cell Discovery |
| title | Potent and broadly neutralizing antibodies against sarbecoviruses induced by sequential COVID-19 vaccination |
| title_full | Potent and broadly neutralizing antibodies against sarbecoviruses induced by sequential COVID-19 vaccination |
| title_fullStr | Potent and broadly neutralizing antibodies against sarbecoviruses induced by sequential COVID-19 vaccination |
| title_full_unstemmed | Potent and broadly neutralizing antibodies against sarbecoviruses induced by sequential COVID-19 vaccination |
| title_short | Potent and broadly neutralizing antibodies against sarbecoviruses induced by sequential COVID-19 vaccination |
| title_sort | potent and broadly neutralizing antibodies against sarbecoviruses induced by sequential covid 19 vaccination |
| url | https://doi.org/10.1038/s41421-024-00648-1 |
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