Adaptation of SARS-CoV-2 in BALB/c mice for testing vaccine efficacy
Hongjing Gu, Qi Chen, Guan Yang, Lei He, Hang Fan, Yong‐Qiang Deng, Yanxiao Wang, Yue Teng, Zhongpeng Zhao, Yujun Cui, Yuchang Li, Xiao-Feng Li, Jiangfan Li, Na-Na Zhang, Xiaolan Yang, Shaolong Chen, Yan Guo, Guangyu Zhao, Xiliang Wang, Deyan Luo, Hui Wang, Xiao Yang, Yan Li, Gencheng Han, Yuxian He, Xiaojun Zhou, Shusheng Geng, Xiaoli Sheng, Shibo Jiang, Shihui Sun, Cheng‐Feng Qin, Yusen Zhou
Abstract
The ongoing coronavirus disease 2019 (COVID-19) pandemic has prioritized the development of small-animal models for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We adapted a clinical isolate of SARS-CoV-2 by serial passaging in the respiratory tract of aged BALB/c mice. The resulting mouse-adapted strain at passage 6 (called MASCp6) showed increased infectivity in mouse lung and led to interstitial pneumonia and inflammatory responses in both young and aged mice after intranasal inoculation. Deep sequencing revealed a panel of adaptive mutations potentially associated with the increased virulence. In particular, the N501Y mutation is located at the receptor binding domain (RBD) of the spike protein. The protective efficacy of a recombinant RBD vaccine candidate was validated by using this model. Thus, this mouse-adapted strain and associated challenge model should be of value in evaluating vaccines and antivirals against SARS-CoV-2.