Potent and broadly neutralizing antibodies against sarbecoviruses elicited by single ancestral SARS-CoV-2 infection
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 IC<sub>50</sub> 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.
Authors
- Xiaomin Xing (ORCID: https://orcid.org/0009-0003-2933-0003)
- Yuanchen Liu (ORCID: https://orcid.org/0000-0002-7753-9886)
- Lei Sun (ORCID: https://orcid.org/0000-0001-8741-0202)
- Tianyi Qiu (ORCID: https://orcid.org/0000-0003-2619-0298)
- Wentai Ma (ORCID: https://orcid.org/0000-0003-1931-8687)
- Yu Lei (ORCID: https://orcid.org/0000-0002-1610-9479)
- Hin Chu (ORCID: https://orcid.org/0000-0003-2855-9837)
- Shihan Tian
- Ming Gao (ORCID: https://orcid.org/0000-0003-1626-4580)
- Yongjun Guan (ORCID: https://orcid.org/0000-0001-6546-2095)
- Hongjie Yu (ORCID: https://orcid.org/0000-0002-6335-5648)
- Jialu Shi
- Yanjia Chen (ORCID: https://orcid.org/0000-0001-6373-6275)
- Rui Qiao (ORCID: https://orcid.org/0000-0003-0210-2863)
- Xiaoyu Zhao (ORCID: https://orcid.org/0000-0002-0347-9104)
- Xun Wang (ORCID: https://orcid.org/0000-0002-5303-8913)
- Chen Li (ORCID: https://orcid.org/0000-0003-0704-8763)
- Pengfei Wang (ORCID: https://orcid.org/0000-0003-2454-7652)
- Wen Shuhua
- Jiayan Li (ORCID: https://orcid.org/0009-0000-3436-0483)
- Yingxue Xue
- Yajie Wang
Institutions
- Fudan University (CN)
- Beijing Institute of Genomics (CN)
- Zhongshan Hospital (CN)
- Pudong Medical Center (CN)
- Sino Biological (China) (CN)
- Research & Diagnostic Antibodies (United States) (US)
- HKU-Pasteur Research Pole (HK)
- Obstetrics and Gynecology Hospital of Fudan University (CN)
- Guangzhou Eighth People's Hospital (CN)
- University of Chinese Academy of Sciences (CN)
- University of Hong Kong (HK)
- Guangzhou Medical University (CN)
Publication Details
- Journal
- Communications Biology
- Published
- 2025-03-06
- DOI
- https://doi.org/10.1038/s42003-025-07769-7
- Citations
- 13
- Primary Topic
- SARS-CoV-2 and COVID-19 Research
- Type
- article
- Field-Weighted Citation Impact
- 18.15