Chondroitin Sulphate A Binding Domains: Potential Vaccine for Malaria
Posted Feb 27 2011 7:00pm
Description of Invention: The subject invention is related to a potential vaccine against malaria, and in particular to a vaccine that can prevent malaria infection in pregnant women. The invention relates to the identification of chondroitin sulphate A (CSA) binding domains in var2CSA homologs from different parasite strains. Malaria in pregnancy is a serious complication associated with the parasitized erythrocyte (PE) sequestration in the placenta. With successive pregnancies, pregnant women develop antibodies that recognize placental variants worldwide suggesting these isolates express conserved determinants. Plasmodium falciparum encodes multiple copies of an erythrocyte surface adhesion ligands called var genes. Recent work suggests that two different var genes (var1CSA and var2CSA) could have an important role in PE binding to chondroitin sulphate A (CSA), a primary placental adherence receptor. It has now been shown that var2CSA is transcribed in CSA-binding parasites and that the disruption of var2CSA results in the inability of the parasites to recover the CSA-binding phenotype. Furthermore, when expressed in Chinese hamster ovary (CHO) cells, three Duffy binding-like domains (DBL2-X, DBL3-X and DBL6-epsilon) from var2CSA revealed strong and specific binding to CSA. The identification of multiple binding domains in var2CSA is envisioned as forming the basis of a vaccine against malaria, especially in pregnancy.