• James Brett Case, Paul W Rothlauf, Rita E Chen, Natasha M Kafai, Julie M Fox, Brittany K Smith, Swathi Shrihari, Broc T McCune, Ian B Harvey, Shamus P Keeler, Louis-Marie Bloyet, Haiyan Zhao, Meisheng Ma, Lucas J Adams, Emma S Winkler, Michael J Holtzman, Daved H Fremont, Sean P J Whelan, and Michael S Diamond.
• Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
• Cell Host Microbe. 2020 Sep 9; 28 (3): 465-474.e4.

AbstractSevere 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.Copyright © 2020 Elsevier Inc. All rights reserved.

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