CD8+ T cells (cytotoxic/suppressors) are required for protection in mice immunized with malaria sporozoites.

In recent malaria sporozoite vaccine trials in humans and mice, antibodies to the sporozoite coat protein have given only modest protection against sporozoite challenge. In contrast, irradiated sporozoites can protect mice against massive sporozoite infections. Evidence suggests that immunity in these mice is mediated by T cells. To identify the mechanism of immunity, we used monoclonal antibodies specific for either the CD4 or CD8 molecule to selectively deplete sporozoite-immunized mice of T-cell subsets. Though in vivo depletion of CD4+ T cells did not reduce immunity, depletion of CD8+ T cells abolished protection. Monoclonal antibody treatment did not affect anti-sporozoite antibody levels. Our data indicate that cytotoxic T cells are critical for immunity to large numbers of sporozoites and suggest that vaccine development should be reoriented toward stimulating cellular as well as humoral immunity.