Malaria affects hundreds of millions of people and causes over 600,000 deaths each year. One of the reasons malaria remains such a large global health problem is that there is not a highly effective vaccine. New ways of vaccinating people will be instrumental in helping eliminate malaria. We have shown previously that curing liver stage parasites with novel antimalarials prevents malaria disease and death (Favuzza et al Cell Host & Microbe 2020). We have subsequently shown that re-infecting previously drug-cured animals results in no malaria for up to 2 years later because they were completely immune. This project will identify how animals cured of their Plasmodium liver infections become immune to reinfection by studying humoral and cellular responses to the vaccine and identifying novel protective antigens.