Class II-Restricted Protective Immunity Induced by Malaria Sporozoites

Abstract

The irradiated-sporozoite vaccine elicits sterile immunity againstPlasmodiumparasites in experimental rodent hosts and human volunteers. Based on rodent malaria models, it has been proposed that CD8⁺T cells are the key protective effector mechanism required in sporozoite-induced immunity. To investigate the role of class II-restricted immunity in protective immunity, we immunized β₂-microglobulin knockout (β₂M^−/−) mice with irradiatedPlasmodium yoeliiorP. bergheisporozoites. Sterile immunity was obtained in the CD8⁺-T-cell-deficient mice immunized with eitherP. bergheiorP. yoeliisporozoites. β₂M^−/−mice with the BALB/c (H-2^d) genetic background as well as those with the C57BL (H-2^b) genetic background were protected. Effector mechanisms included CD4⁺T cells, mediated in part through the production of gamma interferon, and neutralizing antibodies that targeted the extracellular sporozoites. We conclude that in the absence of class I-restricted CD8⁺T cells, sporozoite-induced protective immunity can be effectively mediated by class II-restricted immune effector mechanisms. These results support efforts to develop subunit vaccines that effectively elicit high levels of antibody and CD4⁺T cells to targetPlasmodiumpreerythrocytic stages.