Vesicular stomatitis virus vectored vaccine for SARS-CoV-2

Vesicular stomatitis virus vectored vaccine for SARS-CoV-2

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused millions of human infections and hundreds of thousands of deaths. An effective vaccine is of critical importance in mitigating coronavirus induced disease 2019 (COVID-19) and curtailing the pandemic. Using an infectious molecular clone of vesicular stomatitis virus (VSV), we replaced the glycoprotein gene (G) with the spike gene of SARS-CoV-2 to generate VSV-SARS-CoV-2. Using a variant that expresses eGFP we developed a high-throughput imaging based neutralization assay at biosafety level 2. Using this assay we demonstrate that antibody and soluble ACE2 receptor decoy inhibition of infection correlated exceptionally well with inhibition of a human SARS-CoV-2 isolate. Mice immunized with VSV-SARS-CoV-2 elicits high titers of antibodies that neutralize SARS-CoV-2 infection. Upon challenge with a human isolate of SARS-CoV-2, mice expressing human ACE2 show profoundly reduced viral infection and inflammation in the lung indicating protection against pneumonia. Passive transfer of sera from immunized animals protects naïve mice from SARS-CoV-2 challenge. Further development of VSV-SARS-CoV-2 as a replication-competent vaccine against SARS-CoV-2 is warranted.