“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, De-Yan 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 Zhou2020 (; similar)⁠:

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.