J. Case, P. W. Rothlauf, Rita E. Chen, Natasha M Kafai, J. Fox, Brittany Smith, Swathi Shrihari, B. McCune, Ian B Harvey, Shamus P. Keeler, Louis-Marie Bloyet, Haiyan Zhao, Meisheng Ma, L. J. Adams, Emma S. Winkler, M. Holtzman, D. Fremont, S. Whelan, M. Diamond
Cell Host & Microbe, 2020
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.
Cited by 55 publications.
Field of study: Biology