A SARS-CoV-2 Infection Model in Mice Demonstrates Protection by Neutralizing Antibodies

Cell. 2020 Aug 6;182(3):744-753.e4. doi: 10.1016/j.cell.2020.06.011. Epub 2020 Jun 10.

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a pandemic with millions of human infections. One limitation to the evaluation of potential therapies and vaccines to inhibit SARS-CoV-2 infection and ameliorate disease is the lack of susceptible small animals in large numbers. Commercially available laboratory strains of mice are not readily infected by SARS-CoV-2 because of species-specific differences in their angiotensin-converting enzyme 2 (ACE2) receptors. Here, we transduced replication-defective adenoviruses encoding human ACE2 via intranasal administration into BALB/c mice and established receptor expression in lung tissues. hACE2-transduced mice were productively infected with SARS-CoV-2, and this resulted in high viral titers in the lung, lung pathology, and weight loss. Passive transfer of a neutralizing monoclonal antibody reduced viral burden in the lung and mitigated inflammation and weight loss. The development of an accessible mouse model of SARS-CoV-2 infection and pathogenesis will expedite the testing and deployment of therapeutics and vaccines.

Keywords: COVID-19; SARS-CoV-2; animal model; antibody; coronavirus; inflammation; mice; pathogenesis; pneumonia.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin-Converting Enzyme 2
  • Animals
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Neutralizing / therapeutic use*
  • Antibodies, Viral / therapeutic use*
  • Betacoronavirus / immunology*
  • COVID-19
  • Chlorocebus aethiops
  • Coronavirus Infections / therapy*
  • Coronavirus Infections / virology
  • Disease Models, Animal*
  • Female
  • HEK293 Cells
  • Humans
  • Immunization, Passive / methods
  • Lung / metabolism
  • Lung / virology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Mice, Knockout
  • Pandemics
  • Peptidyl-Dipeptidase A / genetics
  • Peptidyl-Dipeptidase A / metabolism
  • Pneumonia, Viral / therapy*
  • Pneumonia, Viral / virology
  • SARS-CoV-2
  • Transduction, Genetic
  • Vero Cells
  • Viral Load / immunology

Substances

  • Antibodies, Monoclonal
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Ace2 protein, mouse
  • Angiotensin-Converting Enzyme 2