Potent and broadly neutralizing antibodies against sarbecoviruses elicited by single ancestral SARS-CoV-2 infection
Abstract The emergence of various SARS-CoV-2 variants presents challenges for antibody therapeutics, emphasizing the need for more potent and broadly neutralizing antibodies. Here, we employed an unbiased screening approach and successfully isolated two antibodies from individuals with only exposure...
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Nature Portfolio
2025-03-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-025-07769-7 |
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| author | Lei Yu Yajie Wang Yuanchen Liu Xiaomin Xing Chen Li Xun Wang Jialu Shi Wentai Ma Jiayan Li Yanjia Chen Rui Qiao Xiaoyu Zhao Shilei Tian Ming Gao Shuhua Wen Yingxue Xue Tianyi Qiu Hongjie Yu Yongjun Guan Hin Chu Lei Sun Pengfei Wang |
| author_facet | Lei Yu Yajie Wang Yuanchen Liu Xiaomin Xing Chen Li Xun Wang Jialu Shi Wentai Ma Jiayan Li Yanjia Chen Rui Qiao Xiaoyu Zhao Shilei Tian Ming Gao Shuhua Wen Yingxue Xue Tianyi Qiu Hongjie Yu Yongjun Guan Hin Chu Lei Sun Pengfei Wang |
| author_sort | Lei Yu |
| collection | DOAJ |
| description | Abstract The emergence of various SARS-CoV-2 variants presents challenges for antibody therapeutics, emphasizing the need for more potent and broadly neutralizing antibodies. Here, we employed an unbiased screening approach and successfully isolated two antibodies from individuals with only exposure to ancestral SARS-CoV-2. One of these antibodies, CYFN1006-1, exhibited robust cross-neutralization against a spectrum of SARS-CoV-2 variants, including the latest KP.2, KP.3 and XEC, with consistent IC50 values ranging from ~1 to 5 ng/mL. It also displayed broad neutralization activity against SARS-CoV and related sarbecoviruses. Structural analysis revealed that these antibodies target shared hotspot but mutation-resistant epitopes, with their Fabs locking receptor binding domains (RBDs) in the “down” conformation through interactions with adjacent Fabs and RBDs, and cross-linking Spike trimers into di-trimers. In vivo studies conducted in a JN.1-infected hamster model validated the protective efficacy of CYFN1006-1. These findings suggest that antibodies with cross-neutralization activities can be identified from individuals with exclusively ancestral virus exposure. |
| format | Article |
| id | doaj-art-a4f2afee745c43d79627a0c46b321ddf |
| institution | OA Journals |
| issn | 2399-3642 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj-art-a4f2afee745c43d79627a0c46b321ddf2025-08-20T01:57:27ZengNature PortfolioCommunications Biology2399-36422025-03-018111410.1038/s42003-025-07769-7Potent and broadly neutralizing antibodies against sarbecoviruses elicited by single ancestral SARS-CoV-2 infectionLei Yu0Yajie Wang1Yuanchen Liu2Xiaomin Xing3Chen Li4Xun Wang5Jialu Shi6Wentai Ma7Jiayan Li8Yanjia Chen9Rui Qiao10Xiaoyu Zhao11Shilei Tian12Ming Gao13Shuhua Wen14Yingxue Xue15Tianyi Qiu16Hongjie Yu17Yongjun Guan18Hin Chu19Lei Sun20Pengfei Wang21Guangzhou Eighth People’s Hospital, Guangzhou Medical UniversityShanghai Fifth People’s Hospital, Shanghai Institute of Infectious Disease and Biosecurity, Institutes of Biomedical Sciences, Fudan UniversityState Key Laboratory of Emerging Infectious Diseases, Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong KongGuangzhou Eighth People’s Hospital, Guangzhou Medical 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, Shanghai Key Laboratory of Oncology Target Discovery and Antibody Drug Development, 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, Shanghai Key Laboratory of Oncology Target Discovery and Antibody Drug Development, Fudan UniversityState Key Laboratory of Emerging Infectious Diseases, Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong KongBeijing Institute of Genomics, Chinese Academy of Sciences, University of Chinese Academy of Sciences and China National Center for BioinformationShanghai 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, Shanghai Key Laboratory of Oncology Target Discovery and Antibody Drug Development, 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, Shanghai Key Laboratory of Oncology Target Discovery and Antibody Drug Development, 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, Shanghai Key Laboratory of Oncology Target Discovery and Antibody Drug Development, 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, Shanghai Key Laboratory of Oncology Target Discovery and Antibody Drug Development, 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, Shanghai Key Laboratory of Oncology Target Discovery and Antibody Drug Development, Fudan UniversityGuangzhou Eighth People’s Hospital, Guangzhou Medical UniversityChangyuan Funeng (Shanghai) Life Technology Co., Ltd.Changyuan Funeng (Shanghai) Life Technology Co., Ltd.Institute of Clinical Science, Zhongshan Hospital, Shanghai Institute of Infectious Disease and Biosecurity, Intelligent Medicine Institute, Fudan UniversitySchool of Public Health, Fudan University, Key Laboratory of Public Health Safety, Ministry of EducationChangyuan Funeng (Shanghai) Life Technology Co., Ltd.State Key Laboratory of Emerging Infectious Diseases, Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong KongShanghai Fifth People’s Hospital, Shanghai Institute of Infectious Disease and Biosecurity, Institutes of Biomedical Sciences, 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, Shanghai Key Laboratory of Oncology Target Discovery and Antibody Drug Development, Fudan UniversityAbstract The emergence of various SARS-CoV-2 variants presents challenges for antibody therapeutics, emphasizing the need for more potent and broadly neutralizing antibodies. Here, we employed an unbiased screening approach and successfully isolated two antibodies from individuals with only exposure to ancestral SARS-CoV-2. One of these antibodies, CYFN1006-1, exhibited robust cross-neutralization against a spectrum of SARS-CoV-2 variants, including the latest KP.2, KP.3 and XEC, with consistent IC50 values ranging from ~1 to 5 ng/mL. It also displayed broad neutralization activity against SARS-CoV and related sarbecoviruses. Structural analysis revealed that these antibodies target shared hotspot but mutation-resistant epitopes, with their Fabs locking receptor binding domains (RBDs) in the “down” conformation through interactions with adjacent Fabs and RBDs, and cross-linking Spike trimers into di-trimers. In vivo studies conducted in a JN.1-infected hamster model validated the protective efficacy of CYFN1006-1. These findings suggest that antibodies with cross-neutralization activities can be identified from individuals with exclusively ancestral virus exposure.https://doi.org/10.1038/s42003-025-07769-7 |
| spellingShingle | Lei Yu Yajie Wang Yuanchen Liu Xiaomin Xing Chen Li Xun Wang Jialu Shi Wentai Ma Jiayan Li Yanjia Chen Rui Qiao Xiaoyu Zhao Shilei Tian Ming Gao Shuhua Wen Yingxue Xue Tianyi Qiu Hongjie Yu Yongjun Guan Hin Chu Lei Sun Pengfei Wang Potent and broadly neutralizing antibodies against sarbecoviruses elicited by single ancestral SARS-CoV-2 infection Communications Biology |
| title | Potent and broadly neutralizing antibodies against sarbecoviruses elicited by single ancestral SARS-CoV-2 infection |
| title_full | Potent and broadly neutralizing antibodies against sarbecoviruses elicited by single ancestral SARS-CoV-2 infection |
| title_fullStr | Potent and broadly neutralizing antibodies against sarbecoviruses elicited by single ancestral SARS-CoV-2 infection |
| title_full_unstemmed | Potent and broadly neutralizing antibodies against sarbecoviruses elicited by single ancestral SARS-CoV-2 infection |
| title_short | Potent and broadly neutralizing antibodies against sarbecoviruses elicited by single ancestral SARS-CoV-2 infection |
| title_sort | potent and broadly neutralizing antibodies against sarbecoviruses elicited by single ancestral sars cov 2 infection |
| url | https://doi.org/10.1038/s42003-025-07769-7 |
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