@article{203d0648c79c448aa2e583b168261600,
title = "A SARS-CoV-2 Infection Model in Mice Demonstrates Protection by Neutralizing Antibodies",
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",
author = "Hassan, {Ahmed O.} and Case, {James Brett} and Winkler, {Emma S.} and Thackray, {Larissa B.} and Kafai, {Natasha M.} and Bailey, {Adam L.} and McCune, {Broc T.} and Fox, {Julie M.} and Chen, {Rita E.} and Alsoussi, {Wafaa B.} and Turner, {Jackson S.} and Schmitz, {Aaron J.} and Tingting Lei and Swathi Shrihari and Keeler, {Shamus P.} and Fremont, {Daved H.} and Suellen Greco and McCray, {Paul B.} and Stanley Perlman and Holtzman, {Michael J.} and Ellebedy, {Ali H.} and Diamond, {Michael S.}",
note = "Funding Information: This study was supported by NIH contracts and grants (75N93019C00062, R01 AI127828, P01 AI60699, R21 AI139813, U01 AI141990, R01 AI130591, R35 HL145242, and HHSN272201400008C) and the Defense Advanced Research Projects Agency (HR001117S0019). B.T.M is supported by F32 AI138392 and J.B.C. is supported by a Helen Hay Whitney Foundation postdoctoral fellowship. We thank Sean Whelan, Susan Cook, and Jennifer Philips for facilitating the high-containment studies with SARS-CoV-2 and Arthur Kim for purifying the CR3022 anti-S mAb. A.O.H. amplified the adenovirus, designed experiments, and performed intranasal inoculations of adenovirus. J.B.C. propagated the SARS-CoV-2 stocks; developed the focus forming, neutralization, and plaque assays; and performed intranasal inoculations of SARS-CoV-2. A.L.B. designed and constructed the viral qRT-PCR assays and performed intravenous inoculations of SARS-CoV-2. L.B.T. N.M.K. E.S.W. S.S. B.T.M. R.E.C. and J.M.F. performed clinical analysis, tissue harvests, histopathological studies, and viral burden analyses. E.S.W. optimized and performed the flow cytometry staining for hACE2. B.T.M. performed in situ hybridization. S.G, S.P.K. and M.J.H. analyzed the tissue sections for histopathology. S.P. and P.B.M. generated the hACE2 expressing adenovirus. W.B.A. J.S.T. A.J.S. T.L. and A.H.E. generated the anti-SARS-CoV-2 mAbs with reagents from D.H.F. and J.B.C. and R.E.C. performed neutralization assays. E.S.W. A.O.H. and M.S.D. wrote the initial draft, with the other authors providing editing comments. M.S.D. is a consultant for Inbios, Eli Lilly, Vir Biotechnology, NGM Biopharmaceuticals, and on the Scientific Advisory Board of Moderna. A.H.E. is a consultant for Inbios and Fimbrion Therapeutics. The Diamond laboratory has received unrelated funding under sponsored research agreements from Moderna and Emergent BioSolutions. The Ellebedy laboratory has received funding under a sponsored research agreement with Emergent BioSolutions. The Perlman laboratory has received research support from Eli Lilly and AbbVie. Funding Information: This study was supported by NIH contracts and grants ( 75N93019C00062 , R01 AI127828 , P01 AI60699 , R21 AI139813 , U01 AI141990 , R01 AI130591 , R35 HL145242 , and HHSN272201400008C ) and the Defense Advanced Research Projects Agency ( HR001117S0019 ). B.T.M is supported by F32 AI138392 and J.B.C. is supported by a Helen Hay Whitney Foundation postdoctoral fellowship. We thank Sean Whelan, Susan Cook, and Jennifer Philips for facilitating the high-containment studies with SARS-CoV-2 and Arthur Kim for purifying the CR3022 anti-S mAb. Publisher Copyright: {\textcopyright} 2020 Elsevier Inc.",
year = "2020",
month = aug,
day = "6",
doi = "10.1016/j.cell.2020.06.011",
language = "English",
volume = "182",
pages = "744--753.e4",
journal = "Cell",
issn = "0092-8674",
number = "3",
}