Rapid adaptation of SARS-CoV-2 in BALB/c mice: Novel mouse model for vaccine efficacy

Gu, Hongjing; Chen, Qi; Yang, Guan; He, Lei; Fan, Hang; Deng, Yong-Qiang; Wang, Yanxiao; Teng, Yue; Zhao, Zhongpeng; Cui, Yujun; Li, Yuchang; Li, Xiao-Feng; Li, Jiangfan; Zhang, Nana; Yang, Xiaolan; Chen, Shaolong; Zhao, Guangyu; Wang, Xiliang; Luo, Deyan; Wang, Hui; Yang, Xiao; Li, Yan; Han, Gencheng; He, Yuxian; Zhou, Xiaojun; Geng, Shusheng; Sheng, Xiaoli; Jiang, Shibo; Sun, Shihui; Qin, Cheng-Feng; Zhou, Yusen

Coronavirus disease 2019 (COVID-19) threatens global public health and economy. In order to develop safe and effective vaccines, suitable animal models must be established. Here we report the rapid adaption of SARS-CoV-2 in BALB/c mice, based on which a convenient, economical and effective animal model was developed. Specifically, we found that mouse-adapted SARS-CoV-2 at passage 6 (MACSp6) efficiently infected both aged and young wild-type BALB/c mice, resulting in moderate pneumonia as well as inflammatory responses. The elevated infectivity of MACSp6 in mice could be attributed to the substitution of a key residue (N501Y) in the receptorbinding domain (RBD). Using this novel animal model, we further evaluated the in vivo protective efficacy of an RBD-based SARS-CoV-2 subunit vaccine, which elicited highly potent neutralizing antibodies and conferred full protection against SARS-CoV-2 MACSp6 challenge. This novel mouse model is convenient and effective in evaluating the in vivo protective efficacy of SARS-CoV-2 vaccine. Summary This study describes a unique mouse model for SARS-CoV-2 infection and confirms protective efficacy of a SARS-CoV-2 RBD subunit vaccine.