Genetically attenuated P36p-deficient Plasmodium berghei sporozoites confer long-lasting and partial cross-species protection

Abstract

Immunisation with live, radiation-attenuated sporozoites (RAS) or genetically attenuated sporozoites (GAS) of rodent plasmodial parasites protects against subsequent challenge infections. We recently showed that immunisation with Plasmodium berghei GAS that lack the microneme protein P36p protects mice for a period of up to 4 months. Here, we show that the period of full protection induced by p36p(-)-sporozoites lasts 12 and 18 months in C57Bl6 and BALB/c mice, respectively. Full protection is also achieved with three doses of only 1000 p36p(-) (but not RAS) sporozoites. Subcutaneous, intradermal or intramuscular routes of administration also lead to partial protection. In addition, immunisation with either P. berghei RAS- or, to a lesser extent, p36p(-)-sporozoites inhibits parasite intrahepatic development in mice challenged with Plasmodium yoelii sporozoites. Since naturally acquired malaria infections or subunit-based vaccines only induce short-term immune responses, the protection conferred by immunisation with p36p(-)-sporozoites described here further emphasises the potential of GAS as a vaccination strategy for malaria.