Potent neutralizing antibodies from COVID-19 patients define multiple targets of vulnerability

Science. 2020 Aug 7;369(6504):643-650. doi: 10.1126/science.abc5902. Epub 2020 Jun 15.

Abstract

The rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has had a large impact on global health, travel, and economy. Therefore, preventative and therapeutic measures are urgently needed. Here, we isolated monoclonal antibodies from three convalescent coronavirus disease 2019 (COVID-19) patients using a SARS-CoV-2 stabilized prefusion spike protein. These antibodies had low levels of somatic hypermutation and showed a strong enrichment in VH1-69, VH3-30-3, and VH1-24 gene usage. A subset of the antibodies was able to potently inhibit authentic SARS-CoV-2 infection at a concentration as low as 0.007 micrograms per milliliter. Competition and electron microscopy studies illustrate that the SARS-CoV-2 spike protein contains multiple distinct antigenic sites, including several receptor-binding domain (RBD) epitopes as well as non-RBD epitopes. In addition to providing guidance for vaccine design, the antibodies described here are promising candidates for COVID-19 treatment and prevention.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal / immunology*
  • Antibodies, Neutralizing / blood
  • Antibodies, Neutralizing / immunology*
  • Antibodies, Viral / blood
  • Antibodies, Viral / immunology*
  • Antibody Affinity
  • Antigens, Viral / immunology
  • B-Lymphocyte Subsets / immunology
  • Betacoronavirus / immunology*
  • Broadly Neutralizing Antibodies / immunology
  • COVID-19
  • Cell Line, Tumor
  • Coronavirus Infections / immunology*
  • Coronavirus Infections / prevention & control
  • Coronavirus Infections / therapy
  • Epitopes / immunology
  • Female
  • Humans
  • Immunologic Memory
  • Immunophenotyping
  • Male
  • Middle Aged
  • Pandemics / prevention & control
  • Pneumonia, Viral / immunology*
  • Pneumonia, Viral / prevention & control
  • Pneumonia, Viral / therapy
  • Protein Domains
  • Protein Interaction Domains and Motifs / immunology
  • Receptors, Coronavirus
  • Receptors, Virus / metabolism
  • SARS-CoV-2
  • Spike Glycoprotein, Coronavirus / chemistry
  • Spike Glycoprotein, Coronavirus / immunology*

Substances

  • Antibodies, Monoclonal
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Antigens, Viral
  • Broadly Neutralizing Antibodies
  • Epitopes
  • Receptors, Coronavirus
  • Receptors, Virus
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2