New strategies for malaria vaccines.

• Unité de recherche: TPH
• Numéro de projet: 1.05
• Titre du projet anglais: New strategies for malaria vaccines.

Mots-clé (Anglais)

Malaria, Plasmodium falciparum, PfEMP1, antigenic variation, var genes, sequence analysis, vaccine development, field studies

Description succincte (Anglais)

The main aim of the study is the identification of genes coding for adhesive parasite derived molecules responsible for the major pathogenicity in Plasmodium falciparum malaria. The identification of high affinity binders would allow the development of an anti-adhesion vaccine.

Objectifs du projet (Anglais)

The project aims to determine virulence factors in malaria and to identify and validate these as vaccine candidates.

Résumé des résultats (Abstract) (Anglais)

Cytoadherence of Plasmodium falciparum is a major contributor to the pathology of malaria. Adherence to endothelial receptors is mediated by parasite derived proteins termed PfEMP1. PfEMP1 shows antigenic variation and is encoded by the var gene family comprising 50 to 60 genes per haploid genome. We have shown that var genes are localized in two chromosomal areas and that the location can be identified by the regulatory sequence. Using this knowledge we will assay the function of var gene products in relation to their chromosomal location and will assay the micro-evolution of the various groups of antigens from naturally infected individuals. Deducing from the obtained data, we will identifiy conserved genes or gene domains, test their physiological binding properties and further validate their use as vaccine candidates.

Publications / Résultats (Anglais)

Beck, H.P., Felger, I., Huber, W., Steiger, S., Smith, T., Weiss, N., Alonso, P., Tanner, M. 1997 Analysis of multiple Plasmodium falciparum infections in Tanzanian children during the phase III trial of the malaria vaccine SPf66. J. Inf.ect. Dis. 175,: 921-926

Degen, R., Weiss, N., Beck, H.-P. 2000 Plasmodium falciparum: cloned and expressed CIDR domains of PfEMP1 bind to Chondroitin-Sulfate A (CSA). Exp. Parasitol. 95: 113-121.

Kaestli, M., Cortés, A., Lagog, M., Ott, M., Beck, H.-P. Longitudinal assessment of Plasmodium falciparum var gene transcription in naturally infected asymptomatic children in Papua New Guinea. J. Inf. Dis. (submitted)

Voss, T.S., Thompson, K., Waterkeyn, J., Felger, I., Weiss, N., Cowman, A.F., Beck. H.-P. 2000 Genomic distribution and functional characterisation of two distinct and conserved Plasmodium falciparum var gene 5' flanking sequences. Mol. Biochem. Parasitol. 107: 103-15.