A Potently Neutralizing Antibody Protects Mice against SARS-CoV-2 Infection

J Immunol. 2020 Aug 15;205(4):915-922. doi: 10.4049/jimmunol.2000583. Epub 2020 Jun 26.

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for millions of infections and hundreds of thousands of deaths globally. There are no widely available licensed therapeutics against SARS-CoV-2, highlighting an urgent need for effective interventions. The virus enters host cells through binding of a receptor-binding domain within its trimeric spike glycoprotein to human angiotensin-converting enzyme 2. In this article, we describe the generation and characterization of a panel of murine mAbs directed against the receptor-binding domain. One mAb, 2B04, neutralized wild-type SARS-CoV-2 in vitro with remarkable potency (half-maximal inhibitory concentration of <2 ng/ml). In a murine model of SARS-CoV-2 infection, 2B04 protected challenged animals from weight loss, reduced lung viral load, and blocked systemic dissemination. Thus, 2B04 is a promising candidate for an effective antiviral that can be used to prevent SARS-CoV-2 infection.

Publication types

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

MeSH terms

  • Angiotensin-Converting Enzyme 2
  • Animals
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Neutralizing / immunology
  • Antibodies, Neutralizing / pharmacology
  • Antibodies, Neutralizing / therapeutic use*
  • Antibodies, Viral / immunology
  • Antibodies, Viral / pharmacology
  • Antibodies, Viral / therapeutic use*
  • Betacoronavirus / drug effects*
  • COVID-19
  • Chlorocebus aethiops
  • Coronavirus Infections / drug therapy*
  • Coronavirus Infections / immunology*
  • Coronavirus Infections / virology
  • Disease Models, Animal
  • Epitope Mapping
  • Female
  • HEK293 Cells
  • Humans
  • Immunodominant Epitopes / immunology
  • Mice
  • Mice, Inbred C57BL
  • Pandemics
  • Peptidyl-Dipeptidase A / genetics
  • Peptidyl-Dipeptidase A / metabolism
  • Pneumonia, Viral / drug therapy*
  • Pneumonia, Viral / immunology*
  • Pneumonia, Viral / virology
  • Protein Interaction Domains and Motifs / genetics
  • Protein Interaction Domains and Motifs / immunology
  • SARS-CoV-2
  • Spike Glycoprotein, Coronavirus / chemistry
  • Spike Glycoprotein, Coronavirus / metabolism
  • Transfection
  • Vero Cells

Substances

  • Antibodies, Monoclonal
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Immunodominant Epitopes
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Ace2 protein, mouse
  • Angiotensin-Converting Enzyme 2