Researchers who generated a strain of SARS-CoV-2 that can infect mice used it to produce a new mouse model of infection that may help facilitate testing of COVID-19 vaccines and therapeutics. Notably, they used their mouse model to test and confirm the protective efficacy of a COVID-19 vaccine candidate. The ongoing COVID-19 pandemic has prioritized the development of small animal models for SARS-CoV-2. As SARS-CoV-2 does not use mouse ACE2 - the entry point for this virus in humans - mice are thought to be less susceptible. To date, efforts to study virus infection and to evaluate vaccines in mice have required mice to be engineered to express human ACE2. Here, in a different approach, Hongjing Gu and colleagues adapted a strain of SARS-CoV-2 seen in the clinic in the mouse respiratory tract, developing a mutant version (MASCp6) that was able to replicate and cause disease in young and aged mice; both groups showed pneumonia and inflammatory responses after intranasal infection, clinical features seen in human patients. Deep sequencing of the genome of MASCp6 compared to SARS-CoV-2 revealed that a mutation in the spike protein in the virus's receptor binding domain may be responsible for MASCp6's ability to enter mouse ACE2 cells, the authors say. To show their new model's utility for testing vaccine candidates, the researchers immunized female mice with two doses of a recombinant subunit vaccine candidate and then infected them with the adapted virus. Viral loads were lower and no visible clinical symptoms were identified in the vaccinated mice, compared to non-vaccinated controls, they say. Their new mouse-adapted strain of SARS-CoV-2 and the corresponding mouse model of infection add to the repertoire of animal models for studying SARS-CoV-2 transmission. This is important as no single animal model of SARS-CoV-2 currently recapitulates all aspects of human disease.
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Journal
Science