Adaptation of SARS-CoV-2 in BALB/c mice for testing vaccine efficacy
View ORCID ProfileHongjing Gu1,*, View ORCID ProfileQi Chen1,*, View ORCID ProfileGuan Yang2,*, View ORCID ProfileLei He1,*, View ORCID ProfileHang Fan1,*, View ORCID ProfileYong-Qiang Deng1,*, Yanxiao Wang2, Yue Teng1, View ORCID ProfileZhongpeng Zhao1, View ORCID ProfileYujun Cui1, Yuchang Li1, View ORCID ProfileXiao-Feng Li1, View ORCID ProfileJiangfan Li1, View ORCID ProfileNa-Na Zhang1, View ORCID ProfileXiaolan Yang1, Shaolong Chen1, Yan Guo1, View ORCID ProfileGuangyu Zhao1, View ORCID ProfileXiliang Wang1, De-Yan Luo1, Hui Wang1, View ORCID ProfileXiao Yang2, Yan Li3, Gencheng Han3, Yuxian He4, Xiaojun Zhou5, Shusheng Geng6, Xiaoli Sheng6, View ORCID ProfileShibo Jiang7,†,‡, View ORCID ProfileShihui Sun1,†,‡, View ORCID ProfileCheng-Feng Qin1,†,‡, View ORCID ProfileYusen Zhou1,‡,§
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Science 30 Jul 2020:
eabc4730
DOI: 10.1126/science.abc4730
Abstract
The ongoing COVID-19 pandemic has prioritized the development of small animal models for SARS-CoV-2. Herein, 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 (termed MASCp6) showed increased infectivity in mouse lung, and led to interstitial pneumonia and inflammatory responses in both young and aged mice following 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 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.
