Pre-erythrocytic-stage immune effector mechanisms in Plasmodium spp. infections.
The potent protective immunity against malaria induced by immunization of mice and humans with radiation-attenuated Plasmodium spp. sporozoites is thought to be mediated primarily by T-cell responses directed against infected hepatocytes. This has led to considerable efforts to develop subunit vaccines that duplicate this protective immunity, but a universally effective vaccine is still not available and in vitro correlates of protective immunity have not been established. Contributing to this delay has been a lack of understanding of the mechanisms responsible for the protection. There are now data indicating that CD8+ T cells, CD4+ T cells, cytokines, and nitric oxide can all mediate the elimination of infected hepatocytes in vitro and in vivo. By dissecting the protection induced by immunization with irradiated sporozoite, DNA and synthetic peptide-adjuvant vaccines, we have demonstrated that different T-cell-dependent immune responses mediate protective immunity in the same inbred strain of mouse, depending on the method of immunization. Furthermore, the mechanism of protection induced by a single method of immunization may vary among different strains of mice. These data have important implications for the development of pre-erythrocytic-stage vaccines designed to protect a heterogeneous human population, and of assays that predict protective immunity.
Doolan
D L
DL
Malaria Program, Naval Medical Research Institute, Rockville, MD 20852, USA.
Hoffman
S L
SL
D000818:Animals; D004912:Erythrocytes / Q000276:immunology*; D006801:Humans; D008288:Malaria / Q000276:immunology* / Q000469:parasitology; D017780:Malaria Vaccines / Q000276:immunology*; D051379:Mice; D010961:Plasmodium / Q000472:pathogenicity / Q000502:physiology*
D017780:Malaria Vaccines