Andrea Marzi NIAID, National Institutes of Health, Laboratory of Virology, Hamilton, MT, USA
Laboratory of Virology, Division of Intramural Research, NIAID, NIH, Hamilton, MT, USA Animal modeling of ebolaviruses is well established and can be performed in multiple species. Immunocompetent rodent models (mouse, hamster, guinea pig) usually depend on adaptation of wildtype ebolaviruses. Adaptation is associated with genome mutations occurring often in those genes that encode interferon antagonists. These rodent models do not always closely mimic human disease, especially not the mouse model. Nevertheless, rodents remain preferred screening models, but they are not overall predictive of efficacy in nonhuman primates (NHPs) models and ultimately humans. NHP models, in particular cynomolgus and rhesus macaques, are considered the gold standard animal models for ebolaviruses with human-like disease presentation. Cynomolgus macaques are often chosen for vaccine efficacy testing, whereas rhesus macaques are utilized for efficacy testing of antivirals and therapeutics as a prolonged time to death allows for an extended window for intervention. More recently, humanized mice and ferrets have been considered as animal models for ebolaviruses. These models have the advantage of utilizing wildtype ebolavirus isolates, but they are still in their infancies in general. Major disadvantages of the humanized mice are their varying biological make-up the and inconsistency of infection outcome. The lack of tools, varying infection outcome and the more difficult holding and handling are shortcomings of the ferret model. Today, preclinical work for ebolavirus countermeasure development commonly starts with screening in rodent models followed by confirmation in macaque models. VSV-EBOV is a prime example that followed this preclinical development pathway.
Work on ebolaviruses is funded by the Intramural Research Program of the NIAID, NIH.