Immunization with attenuated sporozoites (gamma-irradiated or genetically modified) induces sterile immunity that prevents malaria infection. Attenuated sporozoites maintain their ability to infect the hepatocyte but arrest at an early stage of intrahepatocytic development. To develop a sub-unit vaccine based on this model, we need to identify the targets of immunity. Previous studies in cancer research demonstrated that heat shock protein (HSP)-chaperoned peptides derived from tumor cells can induce immune responses against the same tumor. In this project, HSPVpeptide complexes will be purified from infected hepatocytes and will be used to immunize mice followed by challenge with wild type sporozoites to identify protective HSP-peptide complexes. In parallel peptide sequences will be defined using proteomics tools. The corresponding proteins will be used to identify orthologs expressed by human parasites.
