Experimental human challenge infections can accelerate clinical malaria vaccine development

Malaria is one of the most frequently occurring infectious diseases worldwide, with almost 1 million deaths and an estimated 243 million clinical cases annually. Several candidate malaria vaccines have reached Phase IIb clinical trials, but results have often been disappointing. As an alternative to these Phase IIb field trials, the efficacy of candidate malaria vaccines can first be assessed through the deliberate exposure of participants to the bites of infectious mosquitoes (sporozoite challenge) or to an inoculum of blood-stage parasites (blood-stage challenge). With an increasing number of malaria vaccine candidates being developed, should human malaria challenge models be more widely used to reduce cost and time investments? This article reviews previous experience with both the sporozoite and blood-stage human malaria challenge models and provides future perspectives for these models in malaria vaccine development.