Longitudinal Isolation of Potent Near-Germline SARS-CoV-2-Neutralizing Antibodies from COVID-19 Patients

Cell. 2020 Aug 20;182(4):843-854.e12. doi: 10.1016/j.cell.2020.06.044. Epub 2020 Jul 13.

Abstract

The SARS-CoV-2 pandemic has unprecedented implications for public health, social life, and the world economy. Because approved drugs and vaccines are limited or not available, new options for COVID-19 treatment and prevention are in high demand. To identify SARS-CoV-2-neutralizing antibodies, we analyzed the antibody response of 12 COVID-19 patients from 8 to 69 days after diagnosis. By screening 4,313 SARS-CoV-2-reactive B cells, we isolated 255 antibodies from different time points as early as 8 days after diagnosis. Of these, 28 potently neutralized authentic SARS-CoV-2 with IC100 as low as 0.04 μg/mL, showing a broad spectrum of variable (V) genes and low levels of somatic mutations. Interestingly, potential precursor sequences were identified in naive B cell repertoires from 48 healthy individuals who were sampled before the COVID-19 pandemic. Our results demonstrate that SARS-CoV-2-neutralizing antibodies are readily generated from a diverse pool of precursors, fostering hope for rapid induction of a protective immune response upon vaccination.

Keywords: 2019-nCoV; COVID-19; SARS-CoV-2; monoclonal antibody; neutralizing antibody; single B cell analysis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Neutralizing / genetics
  • Antibodies, Neutralizing / immunology
  • Antibodies, Neutralizing / isolation & purification*
  • Antibodies, Viral / genetics
  • Antibodies, Viral / immunology
  • Antibodies, Viral / isolation & purification*
  • B-Lymphocytes / immunology
  • Betacoronavirus / immunology
  • Coronavirus Infections / immunology*
  • Humans
  • Immunoglobulin Variable Region / genetics
  • Immunoglobulin Variable Region / immunology
  • Immunologic Memory
  • Longitudinal Studies
  • Pandemics
  • Pneumonia, Viral / immunology*
  • Somatic Hypermutation, Immunoglobulin

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Immunoglobulin Variable Region

Supplementary concepts

  • COVID-19
  • severe acute respiratory syndrome coronavirus 2