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

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…

• UD
  U.S. Department of Energy

  Awards: 76SF00515, P41GM103393, DE-AC02, AC02-76SF00515, DE-AC02-
• BA
  Bill and Melinda Gates Foundation

  Award: OPP1170236
• IA
  International AIDS Vaccine Initiative
• NI
  National Institutes of Health

  Awards: UM1 AI44462, K99 AI139445, P41GM103393, DE-AC02-76SF00515
• OO
  Office of Science

  Awards: AC02-76SF00515, P41GM103393, DE-AC02-76SF00515, DE-AC02, 76SF00515
• NI
  National Institute of General Medical Sciences

  Awards: P41GM103393, DE-AC02-76SF00515
• NI
  National Institute of Allergy and Infectious Diseases

  Awards: K99 AI139445, UM1 AI44462, AI139445
• BE
  Basic Energy Sciences

  Awards: DE-AC02, DE-AC02-76SF00515, P41GM103393, 76SF00515, AC02-76SF00515
• BA
  Biological and Environmental Research

  Awards: DE-AC02-76SF00515, P41GM103393
• SN
  SLAC National Accelerator Laboratory

  Awards: P41GM103393, AC02-76SF00515, DE-AC02-76SF00515