FUNDING ORGANIZATION	RESEARCH ORGANIZATION	PROGRAM	DIRECTOR	CITY	COUNTRY	ABSTRACT
	EC	KILIMANJARO CHRISTIAN MEDICAL CENTRE (KCMC)	CLINICAL DEVELOPMENT OF A PFS48/45-BASED MALARIA TRANSMISSION BLOCKING VACCINE	SHEKALAGHE, SEIF	MOSHI	TANZANIA	View
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.
	EC	KILIMANJARO CHRISTIAN MEDICAL CENTRE (KCMC)	MULTI-DRUG RESISTANCE IN MALARIA UNDER COMBINATION THERAPY: ASSESSMENT OF SPECIFIC MARKERS AND DEVELOPMENT OF INNOVATIVE, RAPID AND SIMPLE DIAGNOSTICS.	BOUSEMA, JAN TEUN	MOSHI	TANZANIA	View
This project aims to assess specific P. falciparum genetic markers for resistance to artemisinin-based combinations (ACT), and to develop innovative, rapid and simple diagnostics for malaria and these markers. Specific objectives are: • To develop and evaluate in disease endemic countries accurate low-tech molecular diagnostic tests. • To identify alleles of candidate resistance genes associated with increased transmission success of P. falciparum after ACT treatment in completed clinical trials (endpoints at gametocyte or infected mosquito level). • To conduct ACT treatment trials with transmission endpoints, and measure impact of resistance-associated alleles on gametocyte emergence, and on the infectiousness of gametocyte-positive or randomly-selected treated individuals to Anopheles mosquitoes. • To measure ACT efficacy using in vivo treatment trials, and in vitro drug sensitivity testing of natural parasite isolates. The impact of candidate resistance markers will be measured in patients with treatment failure, and in parasites with reduced in vitro sensitivity. • To develop new low-tech diagnostic tools able to demonstrate the presence of mutations conferring drug resistance in the Plasmodium population, particularly those markers validated by the project. • To investigate commercial value aspects of developed tests. The project will move our knowledge of ACT resistance forward in 2 complementary ways: 1) In order to identify and validate genetic markers for ACT resistance, we will use our unprecedented access to parasites isolated both from ACT-treated individuals and from mosquitoes fed on blood from ACT-treated individuals. 2) we will develop and validate simple tests in new formats for detection of these and other markers of relevance, and for rapid detection of persisting parasites in treated patients. The work is a balanced mix of clinical field work, laboratory research and (commercial) test development and linked to EU initiative EDCTP.