Structural basis of a shared antibody response to SARS-CoV-2

Yuan, Meng; Liu, Hejun; Wu, Nicholas C.; Lee, Chang-Chun D.; Zhu, Xueyong; Zhao, Fangzhu; Huang, Deli; Yu, Wenli; Hua, Yuanzi; Tien, Henry; Rogers, Thomas F.; Landais, Elise; Sok, Devin; Jardine, Joseph G.; Burton, Dennis R.; Wilson, Ian A.

doi:10.1126/science.abd2321

Title: Structural basis of a shared antibody response to SARS-CoV-2

Journal Article · Mon Jul 13 00:00:00 EDT 2020 · Science

DOI:https://doi.org/10.1126/science.abd2321· OSTI ID:1816389

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The Scripps Research Inst., La Jolla, CA (United States). Dept. of Integrative Structural and Computational Biology
The Scripps Research Inst., La Jolla, CA (United States). Dept. of Integrative Structural and Computational Biology; IAVI Neutralizing Antibody Center. Consortium for HIV/AIDS Vaccine Development (CHAVD)
The Scripps Research Inst., La Jolla, CA (United States). Dept. of Immunology and Microbiology
The Scripps Research Inst., La Jolla, CA (United States). Dept. of Immunology and Microbiology; Univ. of California, San Diego, La Jolla, CA (United States). Dept. of Medicine. Division of Infectious Diseases
The Scripps Research Inst., La Jolla, CA (United States). Dept. of Immunology and Microbiology. IAVI Neutralizing Antibody Center; IAVI, New York, NY (United States)
The Scripps Research Inst., La Jolla, CA (United States). IAVI Neutralizing Antibody Center; The Scripps Research Inst., La Jolla, CA (United States). Consortium for HIV/AIDS Vaccine Development (CHAVD); IAVI, New York, NY (United States)
The Scripps Research Inst., La Jolla, CA (United States). IAVI Neutralizing Antibody Center; IAVI, New York, NY (United States)
The Scripps Research Inst., La Jolla, CA (United States). Dept. of Immunology and Microbiology; The Scripps Research Inst., La Jolla, CA (United States). IAVI Neutralizing Antibody Center; The Scripps Research Inst., La Jolla, CA (United States). Consortium for HIV/AIDS Vaccine Development (CHAVD); Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States). Ragon Inst. of Massachusetts General Hospital
The Scripps Research Inst., La Jolla, CA (United States). Dept. of Integrative Structural and Computational Biology. IAVI Neutralizing Antibody Center. Consortium for HIV/AIDS Vaccine Development (CHAVD). The Skaggs Inst. for Chemical Biology

Molecular understanding of neutralizing antibody responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could accelerate vaccine design and drug discovery. We analyzed 294 anti–SARS-CoV-2 antibodies and found that immunoglobulin G heavy-chain variable region 3-53 (IGHV3-53) is the most frequently used IGHV gene for targeting the receptor-binding domain (RBD) of the spike protein. Co-crystal structures of two IGHV3-53–neutralizing antibodies with RBD, with or without Fab CR3022, at 2.33- to 3.20-angstrom resolution revealed that the germline-encoded residues dominate recognition of the angiotensin I converting enzyme 2 (ACE2)–binding site. This binding mode limits the IGHV3-53 antibodies to short complementarity-determining region H3 loops but accommodates light-chain diversity. These IGHV3-53 antibodies show minimal affinity maturation and high potency, which is promising for vaccine design. Knowledge of these structural motifs and binding mode should facilitate the design of antigens that elicit this type of neutralizing response.

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Research Organization:: The Scripps Research Inst., La Jolla, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES)

Grant/Contract Number:: AC02-76SF00515

OSTI ID:: 1816389

Journal Information:: Science, Vol. 369, Issue 6507; ISSN 0036-8075

Publisher:: AAASCopyright Statement

Country of Publication:: United States

Language:: English

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