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bioRxiv · 10.1101/2020.07.09.196386

Replication-competent vesicular stomatitis virus vaccine vector protects against SARS-CoV-2-mediated pathogenesis

James Brett Case·Paul Rothlauf·Rita E. Chen·Natasha Kafai·Julie M. Fox·Swathi Shrihari·Broc T. McCune·Ian B. Harvey·Brittany Smith·Shamus Keeler·Louis-Marie Bloyet·Emma S Winkler·Michael J. Holtzman·Daved H. Fremont·Sean P. J. Whelan·Michael S. Diamond
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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 naive 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.

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James Brett Case, Paul Rothlauf, Rita E. Chen, Natasha Kafai, Julie M. Fox, Swathi Shrihari, Broc T. McCune, Ian B. Harvey, Brittany Smith, Shamus Keeler, Louis-Marie Bloyet, Emma S Winkler, Michael J. Holtzman, Daved H. Fremont, Sean P. J. Whelan, Michael S. Diamond. 2020-07-10. Replication-competent vesicular stomatitis virus vaccine vector protects against SARS-CoV-2-mediated pathogenesis. https://doi.org/10.1101/2020.07.09.196386

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