T cell memory allows for the rapid generation of effective immune responses to previously encountered pathogens. Most memory T cells recirculate through the body and require time to accumulate in tissues upon reinfection. The short duration of the hepatic stage of Plasmodium parasites demands an extremely fast and effective immune response for protection, and hence circulating memory T cells are relatively inefficient at controlling liver-stage malaria infection. We have established that a newly defined subset of memory T cells, the tissue resident memory T cells (TRM), remain in the liver for extended periods of time and constantly survey the hepatic sinusoids, being able to provide efficient protection against malaria. By combining dendritic cell priming and antigen recognition on hepatocytes we generated a novel vaccination strategy, called “prime-and-trap”, that induced the formation of vast numbers of liver TRM cells. Using TCR transgenic PbT-I cells, we showed that prime-and-trap vaccination provides high levels of sterilizing immunity against sporozoite doses almost 50 times higher than those occurring upon natural mosquito transmission, and that sterile protection can be maintained in most mice for at least a fourth of their life span after one single immunization. Using a mass spectrometry approach, we discovered a highly immunogenic H-2Kb epitope within the putative 60S ribosomal protein L6-2 (RPL6) of Plasmodium berghei ANKA. This protein, constitutively expressed during liver and blood stage infection, is conserved across malaria parasite species. Prime-and-trap vaccination targeting this antigen induced the formation of an endogenous population of liver Trm cells that was highly protective against sporozoite challenge. These results demonstrate the feasibility of obtaining persisting, efficient protection against malaria through subunit vaccination aimed at the generation of endogenous liver Trm cells and describe a novel, protective liver stage target for vaccination.