The world needs a highly effective pre-erythrocytic vaccine for malaria prevention. Immunocompetent animal models are needed to test candidate vaccines targeting the most lethal species: Plasmodium falciparum (Pf). However, Pf does not infect mice and does not cause blood-stage infections in the common rhesus non-human primate (NHP) model. Although rhesus do not support blood stage infections, our preliminary data shows that parasites actively proliferate in the preceding liver stage, making it possible to monitor liver burden in nave vs. immunized animals by RT-PCR as an efficacy endpoint. This sort of endpoint is well accepted in rodent models, but has not been widely used in NHP studies because the growth of Pf in rhesus livers was unappreciated until now. We propose to establish this model and compare the liver burden in immunologically- nave NHP compared to NHP vaccinated in a pilot study using our ?prime-and-trap? approach that generates protective liver resident memory CD8+ T cells. This model is enabled by high quality diagnostics, and our lab is considered a reference center for molecular detection of malaria parasites ? therefore we are well suited to evaluate the proposed model. The study will (a) provide additional data on use of Pf/rhesus as a useful NHP model for pre-erythrocytic malaria vaccines and (b) provide translational data on our prime-and-trap vaccine to advance this promising vaccine approach and accelerate funding for further translational studies.
Non-human primate (NHP) models are extremely valuable for development of vaccines and drugs. However, in Plasmodium falciparum, NHP models are lacking for efficacy studies of liver-targeted interventions. This pilot study will evaluate the feasibility and robustness of an NHP P. falciparum sporozoite challenge model monitored by parasite nucleic acid testing on liver samples.
