Protective and non-protective CD8 T cell responses against Plasmodium infection (MPF2P.760)

Abstract

Despite decades of research, malaria remains a global health crisis. Currently, subunit vaccine approaches do not provide long-term, sterilizing immunity against Plasmodium infection. Conversely, immunization using whole parasites can confer protection in rodents through eliciting protective CD8 T cell responses, likely against a broad spectrum of Plasmodium antigens. However, it is unknown whether all of these CD8 T cell specificities contribute to protection. Recently, four novel H-2b-restricted Plasmodium-specific CD8 T cell epitopes were described from the following antigens: GAP50, PbT, S20, and TRAP. Here, we show that priming with peptide-loaded mature dendritic cells followed by boosting with recombinant L. monocytogenes expressing these epitopes results in memory antigen-specific CD8 T cell responses constituting 5-40% of the CD8 T cell compartment. To date, only TRAP-specific CD8 T cells generated through this vaccination approach can provide sterilizing immunity following a sporozoite challenge. This result occurs despite similar numbers, function and phenotype for each of the memory CD8 T cell populations. These data suggest that timing of antigen presentation during liver-stage infection coupled with a requirement for direct MHC presentation predicts the protective capacity of a CD8 T cell specificity. These data may aid in identifying novel target antigens to elicit sterilizing protection against Plasmodium infection.