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

Kathryn A RyanKevin R BewleySusan A FotheringhamGillian S SlackPhillip J BrownYper HallNadina I WandAnthony C MarriottBreeze E CavellJulia A TreeLauren AllenMarilyn J AramThomas J BeanEmily BruntKaren R ButtigiegDaniel P CarterRebecca CobbNaomi S CoombesSteve J Findlay-WilsonKerry J GodwinKaren E GoochJade GourietRachel HalkerstonDebbie J HarrisThomas H HenderHolly E HumphriesLaura HunterCatherine M K HoChelsea L KennardStephanie LeungStéphanie LongetDidier NgaboKaren L OsmanJemma PatersonElizabeth J PennSteven T PullanEmma RaynerOliver SkinnerKimberley SteedsIrene TaylorT R W TiptonStephen ThomasCarrie TurnerRobert J WatsonNathan R WiblinSue CharltonBassam HallisJulian A HiscoxSimon G P FunnellMike J DennisCatherine J WhittakerMichael G CattonJulian DruceFrancisco J SalgueroMiles W Carroll
Published in: Nature communications (2021)
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 × 106 pfu) and medium (5 × 104 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 × 102 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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