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Title: Neutralizing Antibodies to SARS-CoV-2 Selected from a Human Antibody Library Constructed Decades Ago

Journal Article · · Advanced Science
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  1. ShanghaiTech Univ. (China)
  2. ShanghaiTech Univ. (China); Chinese Academy of Sciences, Shanghai (China); Univ. of Chinese Academy of Sciences, Beijing (China)
  3. The Scripps Research Inst., La Jolla, CA (United States)
  4. Univ. of Oxford (United Kingdom)
  5. Velox Pharmaceuticals, Changzhou (China)
  6. ShOx Science Limited, Shanghai (China)
  7. Oxford Glycobiology Inst. (United Kingdom)
  8. 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 Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Organization:
USDOE Office of Science (SC); National Natural Science Foundation of China (NSFC); China Evergrande Group; Shanghai Local Grant
Grant/Contract Number:
AC02-06CH11357; 31500632; 2020GIRHHMS05; ZJ2020-ZD-004
OSTI ID:
1844715
Alternate ID(s):
OSTI ID: 1847711
Journal Information:
Advanced Science, Vol. 9, Issue 1; ISSN 2198-3844
Publisher:
WileyCopyright Statement
Country of Publication:
United States
Language:
ENGLISH

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