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journal article·2022-01Open access

Neutralizing Antibodies to SARS‐CoV‐2 Selected from a Human Antibody Library Constructed Decades Ago

Min Qiang, Peixiang Ma, Yu Li, Hejun Liu, Adam Harding, Chenyu Min, Fulian Wang, Lili Liu, Meng Yuan, Qun Ji, Pingdong Tao, Xiaojie Shi, Zhean Li, Teng Li, Xian Wang, Yu Zhang, Nicholas C. Wu, Chang‐Chun D. Lee, Xueyong Zhu, Javier Gilbert‐Jaramillo, Chuyue Zhang, Abhishek Saxena, Xingxu Huang, Hou Wang, William James, Raymond A. Dwek, Ian A. Wilson, Guang Yang, Richard A. Lerner

Advanced Science· Volume 9· Issue 1
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Abstract

Abstract 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.
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Research context

OpenAlex topics: Monoclonal and Polyclonal Antibodies Research · SARS-CoV-2 and COVID-19 Research · CAR-T cell therapy research

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Shanghai Institute for Advanced Immunochemical Studies ShanghaiTech University Shanghai 201210 P. R. China

School of Life Science and Technology ShanghaiTech University Shanghai 201210 P. R. China

Institute of Biochemistry and Cell Biology Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Shanghai 200031 P. R. China

University of Chinese Academy of Sciences Beijing 100049 P. R. China

Department of Integrative Structural and Computational Biology The Scripps Research Institute La Jolla CA 92037 USA

Sir William Dunn School of Pathology University of Oxford Oxford OX1 3RE UK

Velox Pharmaceuticals Changzhou 213000 P. R. China

ShOx Science Limited Shanghai 200135 P. R. China

Department of Biochemistry Oxford Glycobiology Institute South Parks Road Oxford OX1 3QU UK

The Skaggs Institute for Chemical Biology The Scripps Research Institute La Jolla CA 92037 USA

Department of Chemistry The Scripps Research Institute La Jolla CA 92037 USA

Funding

National Natural Science Foundation of China · JPB Foundation · Bill and Melinda Gates Foundation

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