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.; Han, G.; He, Y.; Zhou, X.; Geng, S.; Sheng, X.; Shi, B.; Sun, S.; Qin, C.-F.; Zhou, Y.

doi:10.1101/2020.05.02.073411

bioRxiv · 10.1101/2020.05.02.073411

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.·Han, G.·He, Y.·Zhou, X.·Geng, S.·Sheng, X.·Shi, B.·Sun, S.·Qin, C.-F.·Zhou, Y.

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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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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., Han, G., He, Y., Zhou, X., Geng, S., Sheng, X., Shi, B., Sun, S., Qin, C.-F., Zhou, Y.. 2020-05-02. Rapid adaptation of SARS-CoV-2 in BALB/c mice: Novel mouse model for vaccine efficacy. https://doi.org/10.1101/2020.05.02.073411

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