Isolation of potent SARS-CoV-2 neutralizing antibodies and protection from disease in a small animal model

Science. 2020 Aug 21;369(6506):956-963. doi: 10.1126/science.abc7520. Epub 2020 Jun 15.

Abstract

Countermeasures to prevent and treat coronavirus disease 2019 (COVID-19) are a global health priority. We enrolled a cohort of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-recovered participants, developed neutralization assays to investigate antibody responses, adapted our high-throughput antibody generation pipeline to rapidly screen more than 1800 antibodies, and established an animal model to test protection. We isolated potent neutralizing antibodies (nAbs) to two epitopes on the receptor binding domain (RBD) and to distinct non-RBD epitopes on the spike (S) protein. As indicated by maintained weight and low lung viral titers in treated animals, the passive transfer of a nAb provides protection against disease in high-dose SARS-CoV-2 challenge in Syrian hamsters. The study suggests a role for nAbs in prophylaxis, and potentially therapy, of COVID-19. The nAbs also define protective epitopes to guide vaccine design.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Angiotensin-Converting Enzyme 2
  • Animals
  • Antibodies, Monoclonal* / blood
  • Antibodies, Monoclonal* / immunology
  • Antibodies, Monoclonal* / isolation & purification
  • Antibodies, Monoclonal* / therapeutic use
  • Antibodies, Neutralizing* / blood
  • Antibodies, Neutralizing* / immunology
  • Antibodies, Neutralizing* / isolation & purification
  • Antibodies, Neutralizing* / therapeutic use
  • Antibodies, Viral* / blood
  • Antibodies, Viral* / immunology
  • Antibodies, Viral* / isolation & purification
  • Antibodies, Viral* / therapeutic use
  • Antibody Affinity
  • Antibody Specificity
  • Betacoronavirus / immunology*
  • Betacoronavirus / physiology
  • Binding Sites
  • COVID-19
  • Cell Line
  • Coronavirus Infections / immunology*
  • Coronavirus Infections / prevention & control*
  • Coronavirus Infections / therapy
  • Coronavirus Infections / virology
  • Disease Models, Animal
  • Epitopes
  • Female
  • Humans
  • Immunization, Passive
  • Lung / virology
  • Male
  • Mesocricetus
  • Middle Aged
  • Neutralization Tests
  • Pandemics / prevention & control*
  • Peptidyl-Dipeptidase A / metabolism
  • Pneumonia, Viral / immunology*
  • Pneumonia, Viral / prevention & control*
  • Pneumonia, Viral / therapy
  • Pneumonia, Viral / virology
  • Protein Domains
  • SARS-CoV-2
  • Spike Glycoprotein, Coronavirus / chemistry
  • Spike Glycoprotein, Coronavirus / immunology
  • Spike Glycoprotein, Coronavirus / metabolism
  • Viral Load
  • Virus Replication

Substances

  • Antibodies, Monoclonal
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Epitopes
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2

Supplementary concepts

  • COVID-19 serotherapy