| Malaria vaccines are needed to reduce the unacceptably high burden of disease and death in particular in the lowest income countries. Malaria vaccines aim at interruption of the life cycle of the parasite Plasmodium falciparum by induced immune responses in the humans. Transmission-blocking (TB) vaccines specifically aim at an arrest sexual stage development preventing the generation of infectious mosquitoes. TBMVs are the most effective tools for reduction of the spread of malaria in the population. This is indispensible for sustained control, elimination and eventually eradication.Pfs48/45 is the most advanced EU-developed malaria TB vaccine candidate. PF10C is a subunit of Pfs48/45 that has been produced with >95% purity inducing functional TB antibodies in 90% of the mice. Objectives: 1) Manufacture PF10C at cGMP grade; 2)Conduct a Phase 1a clinical trial with PF10C in Europe; 3)Prepare for clinical trials with PF10C in Africa. Workplan: PF10C production will be optimized and up-scaled for release of clinical grade batches for human trials. In preclinical studies a PF10C/Alum platform will be the basis for addition of novel adjuvants for final formulation. Next, a Phase Ia trial will be conducted in Europe for safety, immunogenicity and efficacy of TB antibodies in a membrane feeding assay. To rapidly move clinical testing to Africa, preparation for Phase Ib and II will be concomitantly initiated including training of a clinical team. A Phase II trial of a malaria TB vaccine will require a specific design. Important transmission parameters will be collected and introduced in a mathematical model to study the possible impact on transmission in the selected study area followed by a development of a clinical trial protocol. Milestones: 1) Safety, immunogenicity and TB antibody capacity induced by the PF10C vaccine in European volunteers; 2) Protocols and team for Phase I and II clinical trials with PF10C in Africa in place. |
