@article{9f6d2da61fb1471b89c1f29ba5abe5d9,
title = "Replication-Competent Vesicular Stomatitis Virus Vaccine Vector Protects against SARS-CoV-2-Mediated Pathogenesis in Mice",
abstract = "Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused millions of human infections, and an effective vaccine is critical to mitigate coronavirus-induced disease 2019 (COVID-19). Previously, we developed a replication-competent vesicular stomatitis virus (VSV) expressing a modified form of the SARS-CoV-2 spike gene in place of the native glycoprotein gene (VSV-eGFP-SARS-CoV-2). Here, we show that vaccination with VSV-eGFP-SARS-CoV-2 generates neutralizing immune responses and protects mice from SARS-CoV-2. Immunization of mice with VSV-eGFP-SARS-CoV-2 elicits high antibody titers that neutralize SARS-CoV-2 and target the receptor binding domain that engages human angiotensin-converting enzyme-2 (ACE2). Upon challenge with a human isolate of SARS-CoV-2, mice that expressed human ACE2 and were immunized with VSV-eGFP-SARS-CoV-2 show profoundly reduced viral infection and inflammation in the lung, indicating protection against pneumonia. Passive transfer of sera from VSV-eGFP-SARS-CoV-2-immunized animals also protects naive mice from SARS-CoV-2 challenge. These data support development of VSV-SARS-CoV-2 as an attenuated, replication-competent vaccine against SARS-CoV-2.",
keywords = "COVID-19, SARS-CoV-2, correlates, humoral immunity, immunity, neutralizing antibodies, vaccine, vesicular stomatitis virus",
author = "Case, {James Brett} and Rothlauf, {Paul W.} and Chen, {Rita E.} and Kafai, {Natasha M.} and Fox, {Julie M.} and Smith, {Brittany K.} and Swathi Shrihari and McCune, {Broc T.} and Harvey, {Ian B.} and Keeler, {Shamus P.} and Bloyet, {Louis Marie} and Haiyan Zhao and Meisheng Ma and Adams, {Lucas J.} and Winkler, {Emma S.} and Holtzman, {Michael J.} and Fremont, {Daved H.} and Whelan, {Sean P.J.} and Diamond, {Michael S.}",
note = "Funding Information: This study was supported by NIH contracts and grants ( 75N93019C00062 , HHSN272201700060C and R01 AI127828 , R37 AI059371 , and U01 AI151810 ), the Defense Advanced Research Project Agency ( HR001117S0019 ), NIH R01 AI130591 and R35 HL145242 , the Washington University Institute of Clinical and Translational Sciences grant UL1TR002345 from the National Center for Advancing Translational Sciences (NCATS) of the National Institutes of Health (NIH), and gifts to Washington University. J.B.C. is supported by a Helen Hay Whitney Foundation postdoctoral fellowship. We thank Natalie Thornburg for providing the clinical isolate of SARS-CoV-2, Ahmed Hassan for amplifying the AdV-hACE2 stocks, James Earnest for providing cell culture support, and the Washington University School of Medicine Pulmonary Morphology Core. The content is solely the responsibility of the authors and does not necessarily represent the official view of the NIH. Some of the figures were created by using BioRender.com . Funding Information: M.S.D. is a consultant for Inbios, Vir Biotechnology, and NGM Biopharmaceuticals and is on the Scientific Advisory Board of Moderna. M.J.H. is a member of the Data and Safety Monitoring Board for AstroZeneca and founder of NuPeak Therapeutics. The Diamond laboratory has received funding under sponsored research agreements from Moderna, Vir Biotechnology, and Emergent BioSolutions. The Whelan laboratory has received funding under sponsored research agreements from Vir Biotechnology. S.P.J.W., P.W.R., M.S.D., and J.B.C. have filed a disclosure with Washington University for the recombinant VSV. Funding Information: This study was supported by NIH contracts and grants (75N93019C00062, HHSN272201700060C and R01 AI127828, R37 AI059371, and U01 AI151810), the Defense Advanced Research Project Agency (HR001117S0019), NIH R01 AI130591 and R35 HL145242, the Washington University Institute of Clinical and Translational Sciences grant UL1TR002345 from the National Center for Advancing Translational Sciences (NCATS) of the National Institutes of Health (NIH), and gifts to Washington University. J.B.C. is supported by a Helen Hay Whitney Foundation postdoctoral fellowship. We thank Natalie Thornburg for providing the clinical isolate of SARS-CoV-2, Ahmed Hassan for amplifying the AdV-hACE2 stocks, James Earnest for providing cell culture support, and the Washington University School of Medicine Pulmonary Morphology Core. The content is solely the responsibility of the authors and does not necessarily represent the official view of the NIH. Some of the figures were created by using BioRender.com. J.B.C. designed experiments, propagated the SARS-CoV-2 stocks, and performed VSV immunizations and SARS-CoV-2 challenge experiments. P.W.R. generated the VSV vaccines. J.B.C. R.E.C. N.M.K. J.M.F. S.S. and E.S.W. performed tissue harvests, histopathological studies, and viral burden analyses. B.T.M. performed in situ hybridization. H.Z. M.M. L.J.A. and D.H.F. designed and produced the recombinant S and RBD proteins. I.B.H. and B.K.S. performed ELISAs. S.P.K. and M.J.H. analyzed the tissue sections for histopathology. J.B.C. and R.E.C. performed neutralization assays. L.M.B. generated the VSV-eGFP control. J.B.C. P.W.R. S.P.J.W. and M.S.D. wrote the initial draft, with the other authors providing editing comments. M.S.D. is a consultant for Inbios, Vir Biotechnology, and NGM Biopharmaceuticals and is on the Scientific Advisory Board of Moderna. M.J.H. is a member of the Data and Safety Monitoring Board for AstroZeneca and founder of NuPeak Therapeutics. The Diamond laboratory has received funding under sponsored research agreements from Moderna, Vir Biotechnology, and Emergent BioSolutions. The Whelan laboratory has received funding under sponsored research agreements from Vir Biotechnology. S.P.J.W. P.W.R. M.S.D. and J.B.C. have filed a disclosure with Washington University for the recombinant VSV. Publisher Copyright: {\textcopyright} 2020 Elsevier Inc.",
year = "2020",
month = sep,
day = "9",
doi = "10.1016/j.chom.2020.07.018",
language = "English",
volume = "28",
pages = "465--474.e4",
journal = "Cell Host and Microbe",
issn = "1931-3128",
number = "3",
}