Replication-Competent Vesicular Stomatitis Virus Vaccine Vector Protects against SARS-CoV-2-Mediated Pathogenesis in Mice

James Brett Case, Paul W. Rothlauf, Rita E. Chen, Natasha M. Kafai, Julie M. Fox, Brittany K. Smith, Swathi Shrihari, Broc T. McCune, Ian B. Harvey, Shamus P. Keeler, Louis Marie Bloyet, Haiyan Zhao, Meisheng Ma, Lucas J. Adams, Emma S. Winkler, Michael J. Holtzman, Daved H. Fremont, Sean P.J. Whelan, Michael S. Diamond

Research output: Contribution to journalArticlepeer-review

81 Scopus citations

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.

Original languageEnglish
Pages (from-to)465-474.e4
JournalCell Host and Microbe
Volume28
Issue number3
DOIs
StatePublished - Sep 9 2020

Keywords

  • COVID-19
  • SARS-CoV-2
  • correlates
  • humoral immunity
  • immunity
  • neutralizing antibodies
  • vaccine
  • vesicular stomatitis virus

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