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

JB Case, PW Rothlauf, RE Chen, NM Kafai, JM Fox… - Cell host & …, 2020 - cell.com
JB Case, PW Rothlauf, RE Chen, NM Kafai, JM Fox, BK Smith, S Shrihari, BT McCune…
Cell host & microbe, 2020cell.com
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 …
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.
cell.com