A SARS-CoV-2 infection model in mice demonstrates protection by neutralizing antibodies

Hassan, Ahmed O.; Case, James Brett; Winkler, Emma S.; Thackray, Larissa; Kafai, Natasha M.; Bailey, Adam L.; McCune, Broc T.; Fox, Julie M.; Chen, Rita E.; Al Soussi, Wafaa B.; Turner, Jackson S.; Schmitz, Aaron J.; Lei, Tingting; Shrihari, Swathi; Keeler, Shamus P.; Fremont, Daved H.; Greco, Suellen; McCray, Paul B.; Perlman, Stanley; Holtzman, Michael J.; Ellebedy, Ali H.; Diamond, Michael S.

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.