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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...
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
Nature Publishing Group UK
2021
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| Materias: | |
| 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 |
| _version_ | 1783631911791362048 |
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| author | 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. |
| author_facet | 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. |
| author_sort | Ryan, Kathryn A. |
| collection | PubMed |
| description | 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. |
| format | Online Article Text |
| id | pubmed-7782478 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2021 |
| publisher | Nature Publishing Group UK |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-77824782021-01-11 Dose-dependent response to infection with SARS-CoV-2 in the ferret model and evidence of protective immunity 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. Nat Commun Article 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. Nature Publishing Group UK 2021-01-04 /pmc/articles/PMC7782478/ /pubmed/33398055 http://dx.doi.org/10.1038/s41467-020-20439-y Text en © Crown 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
| spellingShingle | Article 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. Dose-dependent response to infection with SARS-CoV-2 in the ferret model and evidence of protective immunity |
| title | Dose-dependent response to infection with SARS-CoV-2 in the ferret model and evidence of protective immunity |
| title_full | Dose-dependent response to infection with SARS-CoV-2 in the ferret model and evidence of protective immunity |
| title_fullStr | Dose-dependent response to infection with SARS-CoV-2 in the ferret model and evidence of protective immunity |
| title_full_unstemmed | Dose-dependent response to infection with SARS-CoV-2 in the ferret model and evidence of protective immunity |
| title_short | Dose-dependent response to infection with SARS-CoV-2 in the ferret model and evidence of protective immunity |
| title_sort | dose-dependent response to infection with sars-cov-2 in the ferret model and evidence of protective immunity |
| topic | Article |
| url | 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 |
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