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, we need to identify the targets of immunity. Sporozoite cultured axenically for 3 days are morphologically similar to hepatocytes-invaded sporozoite. In collaboration with Sanaria, we compared the proteome of P. falciparum sporozoite maintained in an axenic culture for 3 days to the proteome of salivary gland sporozoites. Mass spectrometry analysis identified a subset of proteins expressed in 3 days-cultured sporozoite but not in salivary gland sporozoites or other parasite stages. In parallel to the effort to identify new vaccine targets, we have been focusing on identifying biomarkers of immunity to liver-stage parasites. Immunization with attenuated sporozoites (-irradiated) and, more recently, chemoprophylaxis vaccination (CVac) regimens induce immunity that prevents malaria infection. Both vaccine approaches induce CD8+T cells and interferon- responses that have been used as markers of protection. Because earlier trials of both approaches induced sterile immunity in all vaccinated individuals, and all had high IFN-, it has not been possible to assess whether IFN is part of the protective mechanism or a surrogate marker of immunity. We applied two proteomics approaches to compare Liver proteome profile using semi-quantitative method in samples collected from nave mice and mice immunized with -irradiated sporozoite.
