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

Abstract 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 dose titration study SARS-CoV-2 in ferret model. After high (5 × 10 6 pfu) medium 4 virus delivered, intranasally, viral RNA shedding upper respiratory tract (URT) observed 6/6 animals, however, only 1/6 ferrets show similar signs after low 2 challenge. Following sequential culls pathological mild multifocal bronchopneumonia approximately 5–15% lung seen on day 3, dosed groups. Ferrets re-challenged, ceased, are fully protected from acute pathology. The endpoints URT replication & distinct pathology most consistently group. This model infection presents clinical disease.