Priming of CD8+ T cell responses following immunization with heat‐killed Plasmodium sporozoites

Protective immune responses against malaria are induced by immunization with radiation‐attenuated Plasmodium sporozoites. In contrast, non‐viable, heat‐killed sporozoites do not induce protection, emphasizing the requirement for live parasites to achieve effective immune responses. Using an experimental system with CD8+ T cells from T cell receptor‐transgenic mice, we analyzed the primary CD8+ T cell responses elicited by heat‐killed inactivated sporozoites. We found that the numbers of specific CD8+ T cells induced were much lower compared to when immunizing with attenuated sporozoites; however, the kinetics of activation and the phenotype of these T cells were similar in both groups. Despite their low frequency after priming, high numbers of specific CD8+ T cells were observed after boosting with a recombinant vaccinia virus. Upon induction of the recall response, the same level of protection was observed when either heat‐killed or attenuated sporozoites were used for priming. We propose that live parasites are not critical for the induction of memory T cell populations against the malaria liver stages.