REDMAL

 

 

Framework programme:

 7

Project number:

HEALTH-F3-2010-242079

EC contribution:

2,999,998 €

Duration:

48 months

Funding scheme :

Focused Research Project

Starting date:

01/03/2010

 

 

Keywords: Malaria, Vaccine, Transmission blocking, Clinical trials, Epidemiology, Pfs48/45, Adjuvants, cGMP

Problem

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.

Aim

The objective of a transmission-blocking malaria vaccine (TBMV) is to prevent the chance for an individual to become infected with Plasmodium parasites by mosquito bites of the Anopheles vector. As a result the spread of malaria in the population will decrease with subsequent reduction of the disease. TBMV are based on sexual or sporogonic-specific antigens and designed to arrest the development of these stages inside the mosquito. They specifically aim at an arrest sexual stage development preventing the generation of infectious mosquitoes. Pfs48/45 is the most advanced EU-developed TBMV candidate. PF10C-MBP is a subunit of Pfs48/45 that has been produced with 95% purity inducing functional transmission blocking antibodies in 90% of the mice.

Workplan:

• Manufacture PF10C-MBP at cGMP grade;
• Conduct a Phase 1a clinical trial with PF10C-MBP in Europe;
• Prepare for clinical trials with PF10C-MBP in Africa.

PF10C-MBP production will be optimized and up-scaled for release of clinical grade batches for human trials. In preclinical studies a PF10C-MBP/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 transmission blocking 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 TBMV 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.