The innovative approach taken by our laboratory, relies on secreted gp96-Ig chaperoning antigenic proteins that are efficiently taken up by activated APCs and cross presented via MHC I to CD8 CTL, thereby stimulating an avid, antigen specific, cytotoxic CD8 T cell response. Here we developed malaria vaccine that relies on secreted gp96-Ig chaperoning Plasmodium falciparum antigenic sporozoite proteins CSP and AMA1. The generation of a powerful, cytotoxic anti sporozoiteCD8 CTL response by the vaccine is expected to provide prophylactic immunity for malaria by removing infected liver cells before sporozoites can replicate and spread to the erythrocyte stage causing parasitemia. In the fourth year, we completed all proposed mouse immunogenicity experiments that addressed the effect of secondary 293-gp96-Ig PfAMA1-PfCSP immunization and induced memory responses as well as we compared the immunogenicity of the 293-gp96-IgPfAMA1-PfCSP vaccine to the immunogenicity of NMRC-M3V-DAd-PfCA vaccine. We found that gp96-Igvaccination provided stronger antigen specific CD8 T cell responses in the liver and uterus compared to NMRC vaccine. Since we have already completed manufacturing of GMP-grade vaccine material, we are ready for non-human primate studies.