PfVIMT · A Multi-stage Malaria Vaccine for Control and Elimination

This proposal responds to the HORIZON 2024 call “EDCTP3 Joint Undertaking: Research on existing Malaria vaccines and development of new promising candidates.”The malaria epidemic will not stop without a safe, efficacious, and affordable vaccine that can interrupt transmission. The first licensed malaria vaccines, RTS,S and R21, will substantially reduce childhood deaths in Africa. We propose to pursue accelerated approval of Pfs230D1+R21, the first multi-stage malaria vaccine to reduce transmission, which will reduce clinical malaria rates and support control and elimination. While R21 kills sporozoites in skin/liver, Pfs230D1 lyses gametes in mosquitoes. In field trials with adults and children, Pfs230D1 reduced mosquito infection rates >75%. Pfs230D1+R21 development relies on in-vivo direct-skin-feeding (DSF) bioassay, that feeds mosquitoes on skin to recapitulate natural parasite transmission, to measure reasonably likely surrogate efficacy endpoints for accelerated licensure. Modelling R21 and Pfs230D1 field efficacy data suggests Pfs230D1+R21 will substantially reduce malaria burden in high-transmission zones, while other simulations predict accelerated elimination in low-transmission zones. Through innovative trial designs and capacity-building, we will pursue EDCTP3 aims: 1) establish safety and efficacy of a multi-stage vaccine to reduce transmission; 2) pursue accelerated approval of Pfs230D1+R21; 3) expand population-wide long-term safety and efficacy data on R21; and 4) generate expertise and data to inform recommendations that expand cGMP and supply chain for vaccines in Africa. The program will expand clinical trial capacity for transmission-blocking interventions, build expertise and evidence to support future vaccine manufacture in Africa, and improve understanding of malaria immunity including correlates of protection. At project end, an approved multi-stage malaria vaccine to reduce transmission will be poised for Phase 4 cluster-randomized trials.