Accelerating the development of next generation malaria vaccines through development of innovative trial designs in malaria-endemic areas. (360G-Wellcome-107499_Z_15_Z)

Malaria remains a public health emergency despite a partially effective pre-erythrocytic malaria vaccine. There is an urgent need to accelerate the development of a more effective multi-stage vaccine. We will use controlled human malaria infection in semi-immune adults (CHMI) to overcome two critical blocks in vaccine development: a) a comprehensive prioritization of antigens associated with blood-stage immunity for vaccine development and b) an adaption of CHMI to test proof-of-concept for tr ansmission blocking vaccines in vivo. We will comprehensively characterize immunity to malaria using > 100 antigens in thousands of semi-immune adults, then select 200 with a range of different immunological profiles, and conduct CHMI studies with serial quantitative PCR to measure the parasite growth rate in vivo and relate this to host immunity. In addition we will vary the parasite dose in CHMI and use low-doses of anti-malarial drugs if necessary to produce gametocytes in vivo and demon strate transmissibility to mosquitoes fed on participants blood. We will use the CHMI studies to test candidate pre-erythrocytic vaccines, blood-stage vaccines and transmission-blocking vaccines.