@article{d00906d0d0bd4c799c9765cea28d7416,
title = "Structural basis of a shared antibody response to SARS-CoV-2",
abstract = "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.",
author = "Meng Yuan and Hejun Liu and Wu, {Nicholas C.} and Lee, {Chang Chun D.} and Xueyong Zhu and Fangzhu Zhao and Deli Huang and Wenli Yu and Yuanzi Hua and Henry Tien and Rogers, {Thomas F.} and Elise Landais and Devin Sok and Jardine, {Joseph G.} and Burton, {Dennis R.} and Wilson, {Ian A.}",
note = "Funding Information: We thank R. Stanfield for assistance in data collection, B. Briney for na{\"i}ve antibody germline analysis, and the staff of Stanford Synchrotron Radiation Laboratory (SSRL) Beamline 12-1 for assistance. This work was supported by the NIH (grant no. K99 AI139445 to N.C.W.), the Bill and Melinda Gates Foundation (grant no. OPP1170236 to I.A.W. and D.R.B.), NIH NIAID CHAVD (grant no. UM1 AI44462 to I.A.W., D.S., and D.R.B.), and the IAVI Neutralizing Antibody Center. Use of the SSRL, SLAC National Accelerator Laboratory, is supported by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences, under contract no. DE-AC02–76SF00515. The SSRL Structural Molecular Biology Program is supported by the DOE Office of Biological and Environmental Research and by the National Institutes of Health, National Institute of General Medical Sciences (including P41GM103393). Publisher Copyright: Copyright {\textcopyright} 2020 The Authors,",
year = "2020",
month = aug,
day = "28",
doi = "10.1126/science.abd2321",
language = "English (US)",
volume = "369",
pages = "1119--1123",
journal = "Science",
issn = "0036-8075",
publisher = "American Association for the Advancement of Science",
number = "6507",
}