Diverse immunoglobulin gene usage and convergent epitope targeting in neutralizing antibody responses to SARS-CoV-2

Cell Rep. 2021 May 11;35(6):109109. doi: 10.1016/j.celrep.2021.109109. Epub 2021 Apr 24.

Abstract

It is unclear whether individuals with enormous diversity in B cell receptor repertoires are consistently able to mount effective antibody responses against SARS-CoV-2. We analyzed antibody responses in a cohort of 55 convalescent patients and isolated 54 potent neutralizing monoclonal antibodies (mAbs). While most of the mAbs target the angiotensin-converting enzyme 2 (ACE2) binding surface on the receptor binding domain (RBD) of SARS-CoV-2 spike protein, mAb 47D1 binds only to one side of the receptor binding surface on the RBD. Neutralization by 47D1 is achieved independent of interfering RBD-ACE2 binding. A crystal structure of the mAb-RBD complex shows that the IF motif at the tip of 47D1 CDR H2 interacts with a hydrophobic pocket in the RBD. Diverse immunoglobulin gene usage and convergent epitope targeting characterize neutralizing antibody responses to SARS-CoV-2, suggesting that vaccines that effectively present the receptor binding site on the RBD will likely elicit neutralizing antibody responses in a large fraction of the population.

Keywords: SARS-CoV-2; convergent epitope targeting; diverse immunoglobulin gene usage; neutralizing antibody.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Monoclonal / immunology
  • Antibodies, Neutralizing / genetics*
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral / immunology
  • Binding Sites / immunology
  • COVID-19 / genetics*
  • COVID-19 / immunology
  • COVID-19 / therapy
  • Epitopes / genetics
  • Epitopes / immunology
  • Female
  • Genes, Immunoglobulin / genetics
  • Genetic Variation / genetics
  • Humans
  • Immunization, Passive / methods
  • Immunoglobulins / genetics*
  • Immunoglobulins / immunology
  • Male
  • Middle Aged
  • Peptidyl-Dipeptidase A / metabolism
  • Protein Binding / immunology
  • Protein Domains / genetics
  • Receptors, Virus / immunology
  • Receptors, Virus / metabolism
  • SARS-CoV-2 / genetics
  • SARS-CoV-2 / immunology
  • SARS-CoV-2 / pathogenicity

Substances

  • Antibodies, Monoclonal
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Epitopes
  • Immunoglobulins
  • Receptors, Virus
  • Peptidyl-Dipeptidase A

Supplementary concepts

  • COVID-19 serotherapy