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

2020; Cell Press; Volume: 182; Issue: 3 Linguagem: Inglês

10.1016/j.cell.2020.06.011

1097-4172

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 Diamond,

Virus-based gene therapy research

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.