Whole-Sporozoite Malaria Vaccines

Whole-sporozoite administration is the sole immunization strategy that has been shown to elicit sterile immunity against malaria. Sporozoite-based immunization aims at eliciting potent pre-erythrocytic immune responses whilst preventing the appearance and progression of the symptomatic blood stages of infection. Following the landmark demonstration that live, Xirradiated sporozoites of a rodent-infective Plasmodium species were able to protect against a new infection, numerous efforts have been undertaken to exploit the potential of whole sporozoite approaches for clinical vaccine development. Such efforts have led to the generation of candidate vaccines based on the attenuation of P. falciparum by irradiation (RAS) or genetic modification (GAP), or on the administration of live, non-attenuated parasites, under a prophylactic drug regimen (CPS). The well established controlled human malaria infection model has proven to be of great value in this endeavor. In this chapter, we provide a historical perspective and discuss major advances in the development of wholesporozoite malaria vaccines, as well as the search for immune mechanisms and correlates of protection.