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Replication-Competent Vesicular Stomatitis Virus Vaccine Vector Protects against SARS-CoV-2-Mediated Pathogenesis in Mice.
Cell Host Microbe. 2020 09 09; 28(3):465-474.e4.CH

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.

Authors+Show Affiliations

Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA; Program in Virology, Harvard Medical School, Boston, MA, USA.Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA; Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO, USA.Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA; Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO, USA.Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO, USA.Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO, USA.Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA; Division of Pulmonary and Critical Care Medicine, Washington University School of Medicine, St. Louis, MO, USA.Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA.Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO, USA.Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO, USA.Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO, USA.Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA; Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO, USA.Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA; Division of Pulmonary and Critical Care Medicine, Washington University School of Medicine, St. Louis, MO, USA.Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA; Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO, USA; Biochemistry & Molecular Biophysics, Washington University School of Medicine, St. Louis, MO, USA; The Andrew M. and Jane M. Bursky Center for Human Immunology & Immunotherapy Programs, Washington University School of Medicine, St. Louis, MO, USA.Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA. Electronic address: spjwhelan@wustl.edu.Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA; Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO, USA; The Andrew M. and Jane M. Bursky Center for Human Immunology & Immunotherapy Programs, Washington University School of Medicine, St. Louis, MO, USA. Electronic address: diamond@wusm.wustl.edu.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32798445

Citation

Case, James Brett, et al. "Replication-Competent Vesicular Stomatitis Virus Vaccine Vector Protects Against SARS-CoV-2-Mediated Pathogenesis in Mice." Cell Host & Microbe, vol. 28, no. 3, 2020, pp. 465-474.e4.
Case JB, Rothlauf PW, Chen RE, et al. Replication-Competent Vesicular Stomatitis Virus Vaccine Vector Protects against SARS-CoV-2-Mediated Pathogenesis in Mice. Cell Host Microbe. 2020;28(3):465-474.e4.
Case, J. B., Rothlauf, P. W., Chen, R. E., Kafai, N. M., Fox, J. M., Smith, B. K., Shrihari, S., McCune, B. T., Harvey, I. B., Keeler, S. P., Bloyet, L. M., Zhao, H., Ma, M., Adams, L. J., Winkler, E. S., Holtzman, M. J., Fremont, D. H., Whelan, S. P. J., & Diamond, M. S. (2020). Replication-Competent Vesicular Stomatitis Virus Vaccine Vector Protects against SARS-CoV-2-Mediated Pathogenesis in Mice. Cell Host & Microbe, 28(3), 465-e4. https://doi.org/10.1016/j.chom.2020.07.018
Case JB, et al. Replication-Competent Vesicular Stomatitis Virus Vaccine Vector Protects Against SARS-CoV-2-Mediated Pathogenesis in Mice. Cell Host Microbe. 2020 09 9;28(3):465-474.e4. PubMed PMID: 32798445.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Replication-Competent Vesicular Stomatitis Virus Vaccine Vector Protects against SARS-CoV-2-Mediated Pathogenesis in Mice. AU - Case,James Brett, AU - Rothlauf,Paul W, AU - Chen,Rita E, AU - Kafai,Natasha M, AU - Fox,Julie M, AU - Smith,Brittany K, AU - Shrihari,Swathi, AU - McCune,Broc T, AU - Harvey,Ian B, AU - Keeler,Shamus P, AU - Bloyet,Louis-Marie, AU - Zhao,Haiyan, AU - Ma,Meisheng, AU - Adams,Lucas J, AU - Winkler,Emma S, AU - Holtzman,Michael J, AU - Fremont,Daved H, AU - Whelan,Sean P J, AU - Diamond,Michael S, Y1 - 2020/07/30/ PY - 2020/07/09/received PY - 2020/07/21/revised PY - 2020/07/27/accepted PY - 2020/8/18/pubmed PY - 2020/9/22/medline PY - 2020/8/18/entrez KW - COVID-19 KW - SARS-CoV-2 KW - correlates KW - humoral immunity KW - immunity KW - neutralizing antibodies KW - vaccine KW - vesicular stomatitis virus SP - 465 EP - 474.e4 JF - Cell host & microbe JO - Cell Host Microbe VL - 28 IS - 3 N2 - 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. SN - 1934-6069 UR - https://www.unboundmedicine.com/medline/citation/32798445/Replication_Competent_Vesicular_Stomatitis_Virus_Vaccine_Vector_Protects_against_SARS_CoV_2_Mediated_Pathogenesis_in_Mice_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1931-3128(20)30421-2 DB - PRIME DP - Unbound Medicine ER -