An update on nonhuman primate usage for drug and vaccine evaluation against filoviruses.

Abstract

Due to their faithful recapitulation of human disease, nonhumanprimates (NHPs) are considered the gold standard for evaluating drugs against Ebolavirus and other filoviruses. The long-term goal is to reduce the reliance on NHPswith more ethical alternatives. In silico simulations and organoidmodels have the potential to revolutionize drug testing by providing accurate,human-based systems that mimic disease processes and drug responses without theethical concerns associated with animal testing. However, as these emergingtechnologies are still in their developmental infancy, NHP models are presentlyneeded for late-stage evaluation of filovirus vaccines and drugs, as theyprovide critical insights into the efficacy and safety of new medicalcountermeasures. In this review, the authors introduce available NHP models andexamine the existing literature on drug discovery for all medically significantfiloviruses in corresponding models. A deliberate shift towards animal-free models is desired to alignwith the 3Rs of animal research. In the short term, the use of NHP models canbe refined and reduced by enhancing replicability and publishingnegative data. Replacement involves a gradual transition, beginning withthe selection and optimization of better small animal models; advancingorganoid systems, and using in silico models to accurately predictimmunological outcomes.