Neutralizing Antibodies to SARS-CoV-2 Selected from a Human Antibody Library Constructed Decades Ago
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- ShanghaiTech Univ. (China)
- ShanghaiTech Univ. (China); Chinese Academy of Sciences, Shanghai (China); Univ. of Chinese Academy of Sciences, Beijing (China)
- The Scripps Research Inst., La Jolla, CA (United States)
- Univ. of Oxford (United Kingdom)
- Velox Pharmaceuticals, Changzhou (China)
- ShOx Science Limited, Shanghai (China)
- Oxford Glycobiology Inst. (United Kingdom)
- ShanghaiTech Univ. (China); Velox Pharmaceuticals, Changzhou (China)
Combinatorial antibody libraries not only effectively reduce antibody discovery to a numbers game, but enable documentation of the history of antibody responses in an individual. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has prompted a wider application of this technology to meet the public health challenge of pandemic threats in the modern era. Herein, a combinatorial human antibody library constructed 20 years before the coronavirus disease 2019 (COVID-19) pandemic is used to discover three highly potent antibodies that selectively bind SARS-CoV-2 spike protein and neutralize authentic SARS-CoV-2 virus. Compared to neutralizing antibodies from COVID-19 patients with generally low somatic hypermutation (SHM), these three antibodies contain over 13–22 SHMs, many of which are involved in specific interactions in their crystal structures with SARS-CoV-2 spike receptor binding domain. The identification of these somatically mutated antibodies in a pre-pandemic library raises intriguing questions about the origin and evolution of these antibodies with respect to their reactivity with SARS-CoV-2.
- Research Organization:
- Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
- Sponsoring Organization:
- USDOE Office of Science (SC); National Natural Science Foundation of China; China Evergrande Group; Shanghai Local Grant
- Grant/Contract Number:
- AC02-06CH11357
- OSTI ID:
- 1844715
- Alternate ID(s):
- OSTI ID: 1847711
- Journal Information:
- Advanced Science, Journal Name: Advanced Science Journal Issue: 1 Vol. 9; ISSN 2198-3844
- Publisher:
- WileyCopyright Statement
- Country of Publication:
- United States
- Language:
- ENGLISH
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