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

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; Stanley Perlman; Michael J Holtzman; Ali H Ellebedy; Michael S Diamond

doi:10.1016/j.cell.2020.06.011

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

Journal article

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

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, …

Cell (Cambridge), Vol.182(3), pp.744-753.e4

08/06/2020

DOI: 10.1016/j.cell.2020.06.011

PMID: 32553273

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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. [Display omitted] •Adenovirus transduction of human ACE2 enables SARS-CoV-2 infection of BALB/c mice•High levels of viral RNA and infectious SARS-CoV-2 accumulate in lungs•Mice transduced with human ACE2 develop viral pneumonia after SARS-CoV-2 infection•Neutralizing mAbs protect from SARS-CoV-2-induced lung infection and inflammation Laboratory mice transduced with adenoviruses encoding human ACE2 are permissive for SARS-CoV-2 and develop pneumonia. Passive transfer of a neutralizing monoclonal antibody reduces lung infection, inflammation, and disease.

COVID-19

pathogenesis

SARS-CoV-2

antibody

pneumonia

inflammation

coronavirus

animal model

mice

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Title: Subtitle: A SARS-CoV-2 Infection Model in Mice Demonstrates Protection by Neutralizing Antibodies
Creators: Ahmed O Hassan - Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA
James Brett Case - Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA
Emma S Winkler - Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA
Larissa B Thackray - Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA
Natasha M Kafai - Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA
Adam L Bailey - Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA
Broc T McCune - Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA
Julie M Fox - Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA
Rita E Chen - Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA
Wafaa B Alsoussi - Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA
Jackson S Turner - Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA
Aaron J Schmitz - Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA
Tingting Lei - Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA
Swathi Shrihari - Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA
Shamus P Keeler - Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA
Daved H Fremont - Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA
Suellen Greco - Department of Comparative Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA
Paul B McCray - Department of Pediatrics, University of Iowa, Iowa City, IA 52242, USA
Stanley Perlman - Department of Pediatrics, University of Iowa, Iowa City, IA 52242, USA
Michael J Holtzman - Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA
Ali H Ellebedy - Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA
Michael S Diamond - Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA
Resource Type: Journal article
Publication Details: Cell (Cambridge), Vol.182(3), pp.744-753.e4
Publisher: Elsevier Inc
DOI: 10.1016/j.cell.2020.06.011
PMID: 32553273
ISSN: 0092-8674
eISSN: 1097-4172
Grant note: DOI: 10.13039/100000002, name: National Institutes of Health; DOI: 10.13039/100000185, name: Defense Advanced Research Projects Agency
Language: English
Date published: 08/06/2020
Academic Unit: Microbiology and Immunology; Pulmonary Medicine; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Infectious Disease (Pediatrics); Internal Medicine
Record Identifier: 9984070872402771

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