Target cell specificity for the invasion of human liver hepatocytes by malaria sporozites is conferred by a receptor-ligand interaction between hepatocytes plasma membrane heparin sulfate proteoglycans (HSPG) and an evolutionarily conserved region in the carboxy terminus of the malaria sporozoite coat protein, the circumsporozoite (CS) protein. The detailed structural requirements for this recognition are however, not fully understood and it may be possible to construct sequences or structural mimics of the conserved Region II-plus which bind the receptor with higher affinity than the native sequence. It is proposed to select such 'mimeotopes' from bacteriophage display libraries for use in experiments on inhibition of malarial infection in vivo and in vitro by blocking the recognition of sporozoite CS by the HSPG hepatocyte receptors.
