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

Highlights

• 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

Summary

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.