A Review of Nonhuman Primate Models of Rift Valley Fever Virus Infection: Progress, Challenge Strains, and Future Directions

Abstract

Rift Valley fever (RVF) is a mosquito-borne viral disease that primarily affects animals, especially ruminants, but has the capacity to infect humans and result in outbreaks. Infection with the causative agent, RVF virus (RVFV), causes severe disease in domestic animals, especially sheep, resulting in fever, anorexia, immobility, abortion, and high morbidity and mortality rates in neonate animals. Humans become infected through exposure to infected animals and, less frequently, directly via a mosquito bite. A greater awareness of RVFV and its epidemic potential has resulted in increased investment in the development of interventions, especially vaccines. There is currently no substitute for the use of animal models in order to evaluate these vaccines. As outbreaks of RVF disease are difficult to predict or model, conducting Phase III clinical trials will likely not be feasible. Therefore, representative animal model systems are essential for establishing efficacy data to support licensure. Nonhuman primate (NHP) species are often chosen due to their closeness to humans, reflecting similar susceptibility and disease kinetics. This review covers the use of NHP models in RVFV research, with much of the work having been conducted in rhesus macaques and common marmosets. The future direction of RVF work conducted in NHP is discussed in anticipation of the importance of it being a key element in the development and approval of a human vaccine.