Adaptation of SARS-CoV-2 in BALB/c mice for testing vaccine efficacy

By Hongjing Gu, Qi Chen, Guan Yang, Lei He, Hang Fan, Yongqiang Deng, Yanxiao Wang, Yue Teng, Zhongpeng Zhao, Yujun Cui and 22 more. Science, 2020

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Modeling SARS-CoV-2 in mice Among the research tools necessary to develop medical interventions to treat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, high on the list are informative animal models with which to study viral pathogenesis. Gu et al. developed a mouse model in which a SARS-CoV-2 strain was infectious and could cause an inflammatory response and moderate pneumonia. Adaptation of this viral strain in the mouse appeared to be dependent on a critical amino acid change, Asn501 to Tyr (N501Y), within the receptor-binding domain of the viral spike protein. The new mouse model was used to study neutralizing antibodies and a vaccine candidate against the virus. Science, this issue p. 1603 A SARS-CoV-2 mouse model is used to study viral responses and the development of vaccine candidates. 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.

Subfields: Animal Science and Zoology, Infectious Diseases

View Paper: https://www.semanticscholar.org/paper/dae74544aea5157407069552505ce6996b283eb7

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