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.

严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 已导致数百万人感染，有效的疫苗对于减轻 2019 年冠状病毒 (COVID-19) 引起的疾病至关重要。此前，我们开发了一种具有复制能力的水泡性口炎病毒（VSV），表达修饰形式的 SARS-CoV-2 刺突基因，代替天然糖蛋白基因（VSV-eGFP-SARS-CoV-2）。在这里，我们表明，接种 VSV-eGFP-SARS-CoV-2 疫苗会产生中和免疫反应，并保护小鼠免受 SARS-CoV-2 感染。用 VSV-eGFP-SARS-CoV-2 免疫小鼠会引发高抗体滴度，中和 SARS-CoV-2 并靶向与人血管紧张素转换酶 2 (ACE2) 结合的受体结合域。在用人类 SARS-CoV-2 分离株攻击后，表达人类 ACE2 并用 VSV-eGFP-SARS-CoV-2 免疫的小鼠显示出肺部病毒感染和炎症显着减少，表明可以预防肺炎。来自 VSV-eGFP-SARS-CoV-2 免疫动物的血清被动转移也可以保护幼鼠免受 SARS-CoV-2 攻击。这些数据支持将 VSV-SARS-CoV-2 开发为针对 SARS-CoV-2 的减毒、具有复制能力的疫苗。