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

Ahmed O. Hassan, James Brett Case, Emma S. Winkler, Larissa 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 Fremont, Suellen Greco, Paul B. McCray, Stanley Perlman, Michael J. HoltzmanAli Ellebedy, Michael S. Diamond

Research output: Contribution to journalArticle

22 Scopus citations

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.

Original languageEnglish
JournalCell
DOIs
StateAccepted/In press - Jan 1 2020

Keywords

  • animal model
  • antibody
  • coronavirus
  • COVID-19
  • inflammation
  • mice
  • pathogenesis
  • pneumonia
  • SARS-CoV-2

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    Hassan, A. O., Case, J. B., Winkler, E. S., Thackray, L., Kafai, N. M., Bailey, A. L., McCune, B. T., Fox, J. M., Chen, R. E., Alsoussi, W. B., Turner, J. S., Schmitz, A. J., Lei, T., Shrihari, S., Keeler, S. P., Fremont, D., Greco, S., McCray, P. B., Perlman, S., ... Diamond, M. S. (Accepted/In press). A SARS-CoV-2 Infection Model in Mice Demonstrates Protection by Neutralizing Antibodies. Cell. https://doi.org/10.1016/j.cell.2020.06.011