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Replication-competent vesicular stomatitis virus vaccine vector protects against SARS-CoV-2-mediated pathogenesis.
Case, James Brett; Rothlauf, Paul W; Chen, Rita E; Kafai, Natasha M; Fox, Julie M; Shrihari, Swathi; McCune, Broc T; Harvey, Ian B; Smith, Brittany; Keeler, Shamus P; Bloyet, Louis-Marie; Winkler, Emma S; Holtzman, Michael J; Fremont, Daved H; Whelan, Sean P J; Diamond, Michael S.
  • Case JB; Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
  • Rothlauf PW; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA.
  • Chen RE; Program in Virology, Harvard Medical School, Boston, MA, USA.
  • Kafai NM; Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
  • Fox JM; Departments of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO, USA.
  • Shrihari S; Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
  • McCune BT; Departments of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO, USA.
  • Harvey IB; Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
  • Smith B; Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
  • Keeler SP; Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
  • Bloyet LM; Departments of Biochemistry & Molecular Biophysics, Washington University School of Medicine, St. Louis, MO, USA.
  • Winkler ES; Departments of Biochemistry & Molecular Biophysics, Washington University School of Medicine, St. Louis, MO, USA.
  • Holtzman MJ; Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
  • Fremont DH; Division of Pulmonary and Critical Care Medicine, Washington University School of Medicine, St. Louis, MO, USA.
  • Whelan SPJ; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA.
  • Diamond MS; Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
bioRxiv ; 2020 Jul 10.
Article in English | MEDLINE | ID: covidwho-663086
Preprint
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ABSTRACT
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused millions of human infections and hundreds of thousands of deaths. Accordingly, an effective vaccine is of critical importance in mitigating coronavirus induced disease 2019 (COVID-19) and curtailing the pandemic. We developed a replication-competent vesicular stomatitis virus (VSV)-based vaccine by introducing a modified form of the SARS-CoV-2 spike gene in place of the native glycoprotein gene (VSV-eGFP-SARS-CoV-2). Immunization of mice with VSV-eGFP-SARS-CoV-2 elicits high titers of antibodies that neutralize SARS-CoV-2 infection 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 expressing human ACE2 and immunized with VSV-eGFP-SARS-CoV-2 show profoundly reduced viral infection and inflammation in the lung indicating protection against pneumonia. Finally, passive transfer of sera from VSV-eGFP-SARS-CoV-2-immunized animals protects naïve mice from SARS-CoV-2 challenge. These data support development of VSV-eGFP-SARS-CoV-2 as an attenuated, replication-competent vaccine against SARS-CoV-2.

Full text: Available Collection: International databases Database: MEDLINE Topics: Vaccines Language: English Year: 2020 Document Type: Article Affiliation country: 2020.07.09.196386

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Full text: Available Collection: International databases Database: MEDLINE Topics: Vaccines Language: English Year: 2020 Document Type: Article Affiliation country: 2020.07.09.196386