Dose-dependent response to infection with SARS-CoV-2 in the ferret model and evidence of protective immunity

Ryan, KA; Bewley, KR; Fotheringham, SA; Slack, GS; Brown, P; Hall, Y; Wand, NI; Marriott, AC; Cavell, BE; Tree, JA; Allen, L; Aram, MJ; Bean, TJ; Brunt, E; Buttigieg, KR; Carter, DP; Cobb, R; Coombes, NS; Findlay-Wilson, SJ; Godwin, KJ; Gooch, KE; Gouriet, J; Halkerston, R; Harris, DJ; Hender, TH; Humphries, HE; Hunter, L; Ho, CMK; Kennard, CL; Leung, S; Longet, S; Ngabo, D; Osman, KL; Paterson, J; Penn, EJ; Pullan, ST; Rayner, E; Skinner, O; Steeds, K; Taylor, I; Tipton, T; Thomas, S; Turner, C; Watson, RJ; Wiblin, NR; Charlton, S; Hallis, B; Hiscox, JA; Funnell, S; Dennis, MJ; Whittaker, CJ; Catton, MG; Druce, J; Salguero, FJ; Carroll, MW

COVID-19 Collection

Journal article

Dose-dependent response to infection with SARS-CoV-2 in the ferret model and evidence of protective immunity

Abstract:: Coronavirus disease (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is currently spreading globally. To overcome the COVID-19 pandemic, preclinical evaluations of vaccines and therapeutics using K18-hACE2 and CAG-hACE2 transgenic mice are ongoing. However, a comparative study on SARS-CoV-2 infection between K18-hACE2 and CAG-hACE2 mice has not been published. In this study, we compared the susceptibility and resistance to SARS-CoV-2 infection between two strains of transgenic mice, which were generated in FVB background mice. K18-hACE2 mice exhibited severe weight loss with definitive lethality, but CAG-hACE2 mice survived; and differences were observed in the lung, spleen, cerebrum, cerebellum, and small intestine. A higher viral titer was detected in the lungs, cerebrums, and cerebellums of K18-hACE2 mice than in the lungs of CAG-hACE2 mice. Severe pneumonia was observed in histopathological findings in K18-hACE2, and mild pneumonia was observed in CAG-hACE2. Atrophy of the splenic white pulp and reduction of spleen weight was observed, and hyperplasia of goblet cells with villi atrophy of the small intestine was observed in K18-hACE2 mice compared to CAG-hACE2 mice. These results indicate that K18-hACE2 mice are relatively susceptible to SARS-CoV-2 and that CAG-hACE2 mice are resistant to SARS-CoV-2. Based on these lineage-specific sensitivities, we suggest that K18-hACE2 mouse is suitable for highly susceptible model of SARS-CoV-2, and CAG-hACE2 mouse is suitable for mild susceptible model of SARS-CoV-2 infection.ope

Publication status:: Published

Peer review status:: Peer reviewed

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APA Style

Ryan, K. A., Bewley, K. R., Fotheringham, S. A., Slack, G. S., Brown, P., Hall, Y., Wand, N. I., Marriott, A. C., Cavell, B. E., Tree, J. A., Allen, L., Aram, M. J., Bean, T. J., Brunt, E., Buttigieg, K. R., Carter, D. P., Cobb, R., Coombes, N. S., Findlay-Wilson, S. J., … Carroll, M. W. (2021). Dose-dependent response to infection with SARS-CoV-2 in the ferret model and evidence of protective immunity. Nature Communications, 12(1), 81–81.

MLA Style

Ryan, KA, et al. “Dose-Dependent Response to Infection with SARS-CoV-2 in the Ferret Model and Evidence of Protective Immunity.” Nature Communications, vol. 12, no. 1, 2021, pp. 81–81.

Chicago Style

Ryan, KA, KR Bewley, SA Fotheringham, et al. 2021. “Dose-Dependent Response to Infection with SARS-CoV-2 in the Ferret Model and Evidence of Protective Immunity.” Nature Communications 12 (1): 81–81.
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