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

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

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 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. Passive transfer of sera from VSV-eGFP-SARS-CoV-2-immunized animals also 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.