| Title: |
Dose-dependent response to infection with SARS-CoV-2 in the ferret model and evidence of protective immunity |
| Authors: |
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 |
| Publisher Information: |
Nature Research |
| Publication Year: |
2026 |
| Collection: |
Oxford University Research Archive (ORA) |
| Description: |
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 |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1038/s41467-020-20439-y |
| Availability: |
https://doi.org/10.1038/s41467-020-20439-y; https://ora.ox.ac.uk/objects/uuid:c5334101-292c-4b93-8f81-37b93ce76c3c |
| Rights: |
info:eu-repo/semantics/openAccess ; CC Attribution (CC BY) |
| Accession Number: |
edsbas.F96E9F4F |
| Database: |
BASE |