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

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.

• Authors: Ahmed O Hassan, James Brett Case, Emma S Winkler, Larissa B Thackray, Natasha M Kafai, Adam L Bailey, Broc T McCune, Julie M Fox, Rita E Chen, Wafaa B Alsoussi, Jackson S Turner, Aaron J Schmitz, Tingting Lei, Swathi Shrihari, Shamus P Keeler, Daved H Fremont, Suellen Greco, Paul B McCray Jr, Stanley Perlman, Michael J Holtzman, Ali H Ellebedy, Michael S Diamond
• Journal: Cell (Cell) Vol. 182 Issue 3 Pg. 744-753.e4 (08 06 2020) ISSN: 1097-4172 [Electronic] United States
• PMID: 32553273 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 Elsevier Inc. All rights reserved.

Chemical References

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

Topics

• 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, virology)
• Disease Models, Animal
• Female
• HEK293 Cells
• Humans
• Immunization, Passive (methods)
• Lung (metabolism, virology)
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Mice, Inbred DBA
• Mice, Knockout
• Pandemics
• Peptidyl-Dipeptidase A (genetics, metabolism)
• Pneumonia, Viral (therapy, virology)
• SARS-CoV-2
• Transduction, Genetic
• Vero Cells
• Viral Load (immunology)