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

Author:

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 XiaoORCID,Li Yan,Han Gencheng,He Yuxian,Zhou Xiaojun,Geng Shusheng,Sheng Xiaoli,Jiang Shibo,Sun Shihui,Qin Cheng-Feng,Zhou Yusen

Abstract

AbstractCoronavirus 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.SummaryThis study describes a unique mouse model for SARS-CoV-2 infection and confirms protective efficacy of a SARS-CoV-2 RBD subunit vaccine.

Publisher

Cold Spring Harbor Laboratory

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