Cell Host & Microbe
Volume 28, Issue 3, 9 September 2020, Pages 465-474.e4
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Clinical and Translational Report
Replication-Competent Vesicular Stomatitis Virus Vaccine Vector Protects against SARS-CoV-2-Mediated Pathogenesis in Mice

https://doi.org/10.1016/j.chom.2020.07.018Get rights and content
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Highlights

  • A replicating VSV-SARS-CoV-2 vaccine induces high-titer neutralizing antibodies

  • Infectious SARS-CoV-2 is undetectable in the lung of vaccinated mice post-challenge

  • SARS-CoV-2-induced lung inflammation and pathology is decreased in vaccinated mice

  • Transfer of vaccine-derived immune sera to naive mice protects against SARS-CoV-2

Summary

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

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

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