Evaluation of Vaccines and Therapeutics Against Ebolaviruses in the Domestic Ferret.

Filoviruses, including Ebola and Marburg viruses, have caused periodic outbreaks of severe hemorrhagic disease in humans and nonhuman primates (NHP), resulting in major public health emergencies primarily in endemic areas. Filovirus disease has also been exported to developed nations, where it has been equally disruptive. There are four ebolaviruses (Ebola virus, Sudan virus, Bundibugyo virus, and Taï Forest virus) and two marburgviruses [Marburg virus (MARV) and Ravn virus] known to cause disease in humans, yet vaccines and therapeutics have only been approved for Ebola virus. NHPs have long served as the "gold standard" for medical countermeasure (MCM) evaluation and will most likely be required for regulatory approval for use in humans. However, screening and refinement of MCM dosing regimens are more efficiently and ethically performed in lower-order species such as rodents. However, mouse, hamster, and guinea pig models of filovirus infection require virus adaptation to cause disease in these animal models. Nonadapted filovirus strains can be used in immune-compromised rodent systems (genetic knockouts or humanized mice), but the immune defect must be accounted for when interpreting MCM efficacy. Recently, several groups have described the use of the domestic ferret (Mustela putorius furo) as a model for several ebolaviruses using wild-type (nonadapted) virus, with disease largely reflecting what has been observed in humans and NHPs. Interestingly, no disease has been observed in ferrets challenged with MARV. Here, we describe the use of the domestic ferret for vaccine and therapeutic evaluation against ebolaviruses.