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

被引：130

作者：

Ryan, Kathryn A. ^{[1
]}

Bewley, Kevin R. ^{[1
]}

Fotheringham, Susan A. ^{[1
]}

Slack, Gillian S. ^{[1
]}

Brown, Phillip ^{[1
]}

Hall, Yper ^{[1
]}

Wand, Nadina, I ^{[1
]}

Marriott, Anthony C. ^{[1
]}

Cavell, Breeze E. ^{[1
]}

Tree, Julia A. ^{[1
]}

Allen, Lauren ^{[1
]}

Aram, Marilyn J. ^{[1
]}

Bean, Thomas J. ^{[1
]}

Brunt, Emily ^{[1
]}

Buttigieg, Karen R. ^{[1
]}

Carter, Daniel P. ^{[1
]}

Cobb, Rebecca ^{[1
]}

Coombes, Naomi S. ^{[1
]}

Findlay-Wilson, Steve J. ^{[1
]}

Godwin, Kerry J. ^{[1
]}

Gooch, Karen E. ^{[1
]}

Gouriet, Jade ^{[1
]}

Halkerston, Rachel ^{[1
]}

Harris, Debbie J. ^{[1
]}

Hender, Thomas H. ^{[1
]}

Humphries, Holly E. ^{[1
]}

Hunter, Laura ^{[1
]}

Ho, Catherine M. K. ^{[1
]}

Kennard, Chelsea L. ^{[1
]}

Leung, Stephanie ^{[1
]}

Longet, Stephanie ^{[1
]}

Ngabo, Didier ^{[1
]}

Osman, Karen L. ^{[1
]}

Paterson, Jemma ^{[1
]}

Penn, Elizabeth J. ^{[1
]}

Pullan, Steven T. ^{[1
]}

Rayner, Emma ^{[1
]}

Skinner, Oliver ^{[1
]}

Steeds, Kimberley ^{[1
]}

Taylor, Irene ^{[1
]}

Tipton, Tom ^{[1
]}

Thomas, Stephen ^{[1
]}

Turner, Carrie ^{[1
]}

Watson, Robert J. ^{[1
]}

Wiblin, Nathan R. ^{[1
]}

Charlton, Sue ^{[1
]}

Hallis, Bassam ^{[1
]}

Hiscox, Julian A. ^{[2
]}

Funnell, Simon ^{[1
]}

Dennis, Mike J. ^{[1
]}

机构：

[1] Publ Hlth England PHE, Natl Infect Serv, Salisbury SP4 0JG, Wilts, England

[2] Univ Liverpool, Inst Infect & Global Hlth, Liverpool L69 2BE, Merseyside, England

[3] Peter Doherty Inst Infect & Immun, Victorian Infect Dis Reference Lab, Melbourne, Vic 3000, Australia

[4] Univ Oxford, Nuffield Dept Med, Oxford OX1 3SY, England

来源：

NATURE COMMUNICATIONS | 2021年 / 12卷 / 01期

关键词：

ACUTE RESPIRATORY SYNDROME; INFLUENZA-VIRUS PATHOGENESIS; SARS CORONAVIRUS INFECTION; ANIMAL-MODELS; TRANSMISSION; VACCINE; CATS; MICE;

D O I：

10.1038/s41467-020-20439-y

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 (5x10(6)pfu) and medium (5x10(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 (5x10(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. SARS-CoV-2 induces mild infection in ferret model. Here, Ryan et al. characterise optimal infection dosage inducing upper respiratory tract (UTR) viral shedding, progression time of viral shedding, and pathology in ferrets and finally provide evidence for protection after re-challenge.

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