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

被引：402

作者：

Hassan, Ahmed O. ^{[1
]}

Case, James Brett ^{[1
]}

Winkler, Emma S. ^{[1
,2
]}

Thackray, Larissa B. ^{[1
]}

Kafai, Natasha M. ^{[1
,2
]}

Bailey, Adam L. ^{[2
]}

McCune, Broc T. ^{[1
]}

Fox, Julie M. ^{[1
]}

Chen, Rita E. ^{[1
,2
]}

Alsoussi, Wafaa B. ^{[2
]}

Turner, Jackson S. ^{[2
]}

Schmitz, Aaron J. ^{[2
]}

Lei, Tingting ^{[2
]}

Shrihari, Swathi ^{[1
]}

Keeler, Shamus P. ^{[1
,6
]}

Fremont, Daved H. ^{[2
,5
,7
]}

Greco, Suellen ^{[3
]}

McCray, Paul B., Jr. ^{[8
,9
]}

Perlman, Stanley ^{[8
,9
]}

Holtzman, Michael J. ^{[1
,6
]}

Ellebedy, Ali H. ^{[2
,4
,7
]}

Diamond, Michael S. ^{[1
,2
,4
,7
]}

机构：

[1] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA

[2] Washington Univ, Dept Pathol & Immunol, Sch Med, St Louis, MO 63110 USA

[3] Washington Univ, Dept Comparat Med, Sch Med, St Louis, MO 63110 USA

[4] Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA

[5] Washington Univ, Sch Med, Dept Biochem & Mol Biophys, St Louis, MO 63110 USA

[6] Washington Univ, Div Pulm & Crit Care Med, Sch Med, St Louis, MO 63110 USA

[7] Washington Univ, Sch Med, Andrew M & Jane M Bursky Ctr Human Immunol & Immu, St Louis, MO 63110 USA

[8] Univ Iowa, Dept Pediat, Iowa City, IA 52242 USA

[9] Univ Iowa, Dept Microbiol & Immunol, Iowa City, IA 52242 USA

来源：

CELL | 2020年 / 182卷 / 03期

关键词：

MONOCLONAL-ANTIBODIES; RECEPTOR; ACE2;

D O I：

10.1016/j.cell.2020.06.011

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：744 / +

页数：14

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