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 Jr, Stanley Perlman, Michael J Holtzman, Ali H Ellebedy, Michael S Diamond, 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
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.
Conflict of interest statement
Declaration of Interests M.S.D. is a consultant for Inbios, Eli Lilly, Vir Biotechnology, NGM Biopharmaceuticals, and on the Scientific Advisory Board of Moderna. A.H.E. is a consultant for Inbios and Fimbrion Therapeutics. The Diamond laboratory has received unrelated funding under sponsored research agreements from Moderna and Emergent BioSolutions. The Ellebedy laboratory has received funding under a sponsored research agreement with Emergent BioSolutions. The Perlman laboratory has received research support from Eli Lilly and AbbVie.
Copyright © 2020 Elsevier Inc. All rights reserved.
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