tetano
Editor, Senior Moderator
Cell
. 2020 Jun 10;S0092-8674(20)30742-X.
doi: 10.1016/j.cell.2020.06.011. Online ahead of print.
A SARS-CoV-2 Infection Model in Mice Demonstrates Protection by Neutralizing Antibodies
Ahmed O Hassan[SUP] 1 [/SUP], James Brett Case[SUP] 1 [/SUP], Emma S Winkler[SUP] 2 [/SUP], Larissa B Thackray[SUP] 1 [/SUP], Natasha M Kafai[SUP] 2 [/SUP], Adam L Bailey[SUP] 3 [/SUP], Broc T McCune[SUP] 1 [/SUP], Julie M Fox[SUP] 1 [/SUP], Rita E Chen[SUP] 2 [/SUP], Wafaa B Alsoussi[SUP] 3 [/SUP], Jackson S Turner[SUP] 3 [/SUP], Aaron J Schmitz[SUP] 3 [/SUP], Tingting Lei[SUP] 3 [/SUP], Swathi Shrihari[SUP] 1 [/SUP], Shamus P Keeler[SUP] 4 [/SUP], Daved H Fremont[SUP] 5 [/SUP], Suellen Greco[SUP] 6 [/SUP], Paul B McCray Jr[SUP] 7 [/SUP], Stanley Perlman[SUP] 7 [/SUP], Michael J Holtzman[SUP] 4 [/SUP], Ali H Ellebedy[SUP] 8 [/SUP], Michael S Diamond[SUP] 9 [/SUP]
Affiliations
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.
. 2020 Jun 10;S0092-8674(20)30742-X.
doi: 10.1016/j.cell.2020.06.011. Online ahead of print.
A SARS-CoV-2 Infection Model in Mice Demonstrates Protection by Neutralizing Antibodies
Ahmed O Hassan[SUP] 1 [/SUP], James Brett Case[SUP] 1 [/SUP], Emma S Winkler[SUP] 2 [/SUP], Larissa B Thackray[SUP] 1 [/SUP], Natasha M Kafai[SUP] 2 [/SUP], Adam L Bailey[SUP] 3 [/SUP], Broc T McCune[SUP] 1 [/SUP], Julie M Fox[SUP] 1 [/SUP], Rita E Chen[SUP] 2 [/SUP], Wafaa B Alsoussi[SUP] 3 [/SUP], Jackson S Turner[SUP] 3 [/SUP], Aaron J Schmitz[SUP] 3 [/SUP], Tingting Lei[SUP] 3 [/SUP], Swathi Shrihari[SUP] 1 [/SUP], Shamus P Keeler[SUP] 4 [/SUP], Daved H Fremont[SUP] 5 [/SUP], Suellen Greco[SUP] 6 [/SUP], Paul B McCray Jr[SUP] 7 [/SUP], Stanley Perlman[SUP] 7 [/SUP], Michael J Holtzman[SUP] 4 [/SUP], Ali H Ellebedy[SUP] 8 [/SUP], Michael S Diamond[SUP] 9 [/SUP]
Affiliations
- PMID: 32553273
- DOI: 10.1016/j.cell.2020.06.011
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.