Analysis of a SARS-CoV-2-Infected Individual Reveals Development of Potent Neutralizing Antibodies with Limited Somatic Mutation

Immunity. 2020 Jul 14;53(1):98-105.e5. doi: 10.1016/j.immuni.2020.06.001. Epub 2020 Jun 8.

Abstract

Antibody responses develop following SARS-CoV-2 infection, but little is known about their epitope specificities, clonality, binding affinities, epitopes, and neutralizing activity. We isolated B cells specific for the SARS-CoV-2 envelope glycoprotein spike (S) from a COVID-19-infected subject 21 days after the onset of clinical disease. 45 S-specific monoclonal antibodies were generated. They had undergone minimal somatic mutation with limited clonal expansion, and three bound the receptor-binding domain (RBD). Two antibodies neutralized SARS-CoV-2. The most potent antibody bound the RBD and prevented binding to the ACE2 receptor, while the other bound outside the RBD. Thus, most anti-S antibodies that were generated in this patient during the first weeks of COVID-19 infection were non-neutralizing and target epitopes outside the RBD. Antibodies that disrupt the SARS-CoV-2 S-ACE2 interaction can potently neutralize the virus without undergoing extensive maturation. Such antibodies have potential preventive and/or therapeutic potential and can serve as templates for vaccine design.

Keywords: ACE2; B cells; COVID-19; MERS; SARS; SARS-CoV-2; antibodies; neutralization; receptor-binding domain; spike protein.

Publication types

  • Case Reports

MeSH terms

  • Antibodies, Monoclonal / immunology
  • Antibodies, Neutralizing / immunology*
  • Antibodies, Viral / immunology*
  • B-Lymphocytes / immunology
  • Betacoronavirus / immunology*
  • Binding Sites
  • Coronavirus Infections / immunology
  • Coronavirus Infections / prevention & control
  • Epitopes, B-Lymphocyte / immunology
  • Humans
  • Pandemics / prevention & control
  • Peptidyl-Dipeptidase A / metabolism
  • Pneumonia, Viral / immunology
  • Pneumonia, Viral / prevention & control
  • Protein Binding
  • Receptors, Virus / metabolism
  • Somatic Hypermutation, Immunoglobulin / genetics*
  • Spike Glycoprotein, Coronavirus / immunology*
  • Spike Glycoprotein, Coronavirus / metabolism
  • Viral Vaccines / immunology

Substances

  • Antibodies, Monoclonal
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Epitopes, B-Lymphocyte
  • Receptors, Virus
  • Spike Glycoprotein, Coronavirus
  • Viral Vaccines
  • spike protein, SARS-CoV-2
  • Peptidyl-Dipeptidase A
  • angiotensin converting enzyme 2

Supplementary concepts

  • COVID-19
  • severe acute respiratory syndrome coronavirus 2