期刊
CELL HOST & MICROBE
卷 28, 期 3, 页码 465-+出版社
CELL PRESS
DOI: 10.1016/j.chom.2020.07.018
关键词
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资金
- NIH [75N93019C00062, HHSN272201700060C, R01 AI127828, R37 AI059371, U01 AI151810, HR001117S0019, R01 AI130591, R35 HL145242]
- Defense Advanced Research Project Agency [HR001117S0019]
- Washington University Institute of Clinical and Translational Sciences from the National Center for Advancing Translational Sciences (NCATS) of the National Institutes of Health (NIH) [UL1TR002345]
- Helen Hay Whitney Foundation postdoctoral fellowship
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-conveiling 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.
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