Vaccine-like immunity against malaria by repeated causal-prophylactic treatment of liver-stage Plasmodium parasites.

Liver-stage development of Plasmodium parasites represents a dramatic expansion phase for the malarial parasite between vector transmission and onset of the pathogenic blood-stage cycle. Here, we report that repeated causal-prophylactic primaquine treatment of liver-stage Plasmodium parasites in rodents elicits vaccine-like protective immunity against sporozoite-induced malaria. This regimen differs fundamentally from those involving radiation- or genetically attenuated parasites, in which long-lasting immune responses are dependent on persistence of metabolically active parasites. Pharmacological inhibition of liver-stage parasites in the rodent malaria model offers a potential fast track toward development of a vaccine that targets parasites in preerythrocytic stages.