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

There is a vital need for authentic COVID-19 animal models to enable the pre-clinical evaluation of candidate vaccines and therapeutics. Here we report a dose titration study of SARS-CoV-2 in the ferret model. After a high (5 × 10(6) pfu) and medium (5 × 10(4) pfu) dose of virus is delivered, intran...

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Detalles Bibliográficos
Autores principales: Ryan, Kathryn A., Bewley, Kevin R., Fotheringham, Susan A., Slack, Gillian S., Brown, Phillip, Hall, Yper, Wand, Nadina I., Marriott, Anthony C., Cavell, Breeze E., Tree, Julia A., Allen, Lauren, Aram, Marilyn J., Bean, Thomas J., Brunt, Emily, Buttigieg, Karen R., Carter, Daniel P., Cobb, Rebecca, Coombes, Naomi S., Findlay-Wilson, Steve J., Godwin, Kerry J., Gooch, Karen E., Gouriet, Jade, Halkerston, Rachel, Harris, Debbie J., Hender, Thomas H., Humphries, Holly E., Hunter, Laura, Ho, Catherine M. K., Kennard, Chelsea L., Leung, Stephanie, Longet, Stephanie, Ngabo, Didier, Osman, Karen L., Paterson, Jemma, Penn, Elizabeth J., Pullan, Steven T., Rayner, Emma, Skinner, Oliver, Steeds, Kimberley, Taylor, Irene, Tipton, Tom, Thomas, Stephen, Turner, Carrie, Watson, Robert J., Wiblin, Nathan R., Charlton, Sue, Hallis, Bassam, Hiscox, Julian A., Funnell, Simon, Dennis, Mike J., Whittaker, Catherine J., Catton, Michael G., Druce, Julian, Salguero, Francisco J., Carroll, Miles W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7782478/
https://www.ncbi.nlm.nih.gov/pubmed/33398055
http://dx.doi.org/10.1038/s41467-020-20439-y
Descripción
Sumario:There is a vital need for authentic COVID-19 animal models to enable the pre-clinical evaluation of candidate vaccines and therapeutics. Here we report a dose titration study of SARS-CoV-2 in the ferret model. After a high (5 × 10(6) pfu) and medium (5 × 10(4) pfu) dose of virus is delivered, intranasally, viral RNA shedding in the upper respiratory tract (URT) is observed in 6/6 animals, however, only 1/6 ferrets show similar signs after low dose (5 × 10(2) pfu) challenge. Following sequential culls pathological signs of mild multifocal bronchopneumonia in approximately 5–15% of the lung is seen on day 3, in high and medium dosed groups. Ferrets re-challenged, after virus shedding ceased, are fully protected from acute lung pathology. The endpoints of URT viral RNA replication & distinct lung pathology are observed most consistently in the high dose group. This ferret model of SARS-CoV-2 infection presents a mild clinical disease.

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