Malaria, caused by Plasmodium species, is an unresolved global health burden associated with >200 million cases and >400,000 deaths per year. A recently licensed malaria vaccine designed to limit the initial liver-stage of infection may partially reduce severe malaria in children but highly effective vaccines remain elusive. Development of potent and translatable vaccines against malaria has been hampered by our incomplete understanding of the mechanisms by which the immune system can be trained to control Plasmodium infections. The long-term goals of this new five-year award are to dissect mechanisms leading to generation and function of memory CD8+ T cells that can provide potent immunity to Plasmodium liver-stage infection in order to inform development of effective human vaccines.