EUROMALVAC

European
Malaria
Vaccine
Consortium

EM
VC

xx You are here: Home ->Workplan

Version for printing

The Consortium's projects are at present concerned with the discovery, validation and preclinical development phases of malaria vaccine development. They aim to build on the best of the blood stage malaria vaccine work that has gone before and are based on a clear understanding of the criteria that need to be applied to move a vaccine candidate from the discovery phase to the development phase. An integrated programme is being built up which can consider evidence from numerous fields from sero-epidemiological studies to antigen engineering. The guiding principle is that of the evidence-based decision making.

There is no doubt that European malaria vaccine research has been hampered by the lack of infrastructure to carry basic research through to clinical studies. The consortium is therefore based on an agreed malaria vaccine development pathway and each of its constituent projects work packages is constructed to meet the following basic requirements:

• The application of stringent criteria to define the candidacy of any individual antigen for vaccine development.
• The use of detailed understanding of the biological processes of the parasite-host interaction to define important targets for vaccine development.
• The identification of mechanisms of immune evasion by the parasite and rational approaches to overcome them.

• The use of the very powerful structure-function approach to inform the process of antigen selection and improvement.
• The identification and combination of the best targets for vaccine development to facilitate a multi-stage, multi-component approach.

Project performance and progress are monitored through Consortium meetings which take place every six months.
We have chosen two main areas of malaria parasite biology in the blood stream that can now be exploited for vaccine design. The first is that of parasite invasion of red blood cells and the second is that of the interaction of the infected red blood cell with host cells. The following projects are currently funded and ongoing:

• Pre-clinical development and testing of 1st and 2nd generation Plasmodium falciparum Merozoite Surface Protein 1 (MSP-1) C-terminal-based vaccines, formulated with both alum and new experimental adjuvants. Key objectives are to define the binding sites and biological activities of specific antibodies and thus design more effective vaccine constructs using immunological and biochemical assays correlated with immunity.
• Seroepidemiological studies of human antibody responses to MSP-1 in Africa have suggested that polymorphic and dimorphic sequences of the molecule may play a major role in inducing protective immunity. N-terminal Block 2 sequences are being inserted into Pichia pastoris vectors for expression at high yield, prior to immunogenicity testing and reformulation in adjuvants for immunisation studies in primate models.
• The identification of malaria parasite isolates which express variants of the Plasmodium falciparum erythrocyte membrane proteinÜ1 (PfEMP-1) that are commonly recognised by endemic sera. This involves identification of cross-reactive epitopes and high-frequency variants and mapping epitopes of PfEMP-1.

• Experiments to produce rodent and phage display antibodies against defined PfEMP-1 epitopes and determine whether specific human antibody responses to defined epitopes are associated with protection against disease are also underway.
• Codon re-engineering and scaled up P. pastoris expression of P. falciparum AMA-1 and MSP-1 constructs to obtain pure antigen for vaccine challenge studies in animal models are ongoing.
• Work to scale-up production of Pf antigen R23 for vaccine formulation with alum and other adjuvants and carry out dose-response experiments in animal models has been initiated.
• The collation of the consortium's sera and parasite isolate banks to perform immuno-epidemiological services for all relevant consortium projects is underway.
• Preparation of the Malaria Vaccine Testing Facility at Nijmegen University to carry out clinical trials of malaria vaccines is at an advanced stage and a number of clinical studies are about to begin.

click on flag to return to top