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

Gu, H.; Chen, Q.; Yang, G.; He, L.; Fan, H.; Deng, Y.-q.; Wang, Y.; Teng, Y.; Zhao, Z.; Cui, Y.; Li, Y.; Li, X.-F.; Li, J.; Zhang, N.; Yang, X.; Chen, S.; Zhao, G.; Wang, X.; Luo, D.; Wang, H.; Yang, X.; Li, Y.; Han, G.; He, Y.; Zhou, X.; Geng, S.; Sheng, X.; Shi, B.; Sun, S.; Qin, C.-F.; Zhou, Y.

2020-05-02 microbiology
10.1101/2020.05.02.073411 bioRxiv
Show abstract

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

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