Class II-Restricted Protective Immunity Induced by Malaria Sporozoites

Abstract

ABSTRACT The irradiated-sporozoite vaccine elicits sterile immunity against Plasmodium parasites 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 β 2 -microglobulin knockout (β 2 M −/− ) mice with irradiated Plasmodium yoelii or P. berghei sporozoites. Sterile immunity was obtained in the CD8 + -T-cell-deficient mice immunized with either P. berghei or P. yoelii sporozoites. β 2 M −/− 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 target Plasmodium preerythrocytic stages.