Project description: 

The development of a malaria vaccine that targets the pre-erythrocytic stages of Plasmodium falciparum is based on the assumption that the vaccine would elicit a strong neutralizing humoral immune response directed against surface-exposed sporozoite proteins. This antibody-mediated protection would be achieved either through opsonization and destruction of the invading parasites by macrophages, through the inhibition of a function that is essential for sporozoite invasion of the liver, or both. Additionally, because most free sporozoites persist in the bloodstream for less than 30 minutes and it’s likely that some parasites will have invaded liver cells within a few minutes following an infectious bite, an efficient pre-erythrocytic vaccine should also elicit Cell Mediated Immune (CMI) responses of the CD8+ and CD4+ Th1 type. The role of these T cells is to recognize infected liver cells through parasite-derived processed peptides exposed at the surface of infected hepatocytes in association with the major histocompatibility complexes (MHC) class I and class II. These effector T lymphocytes can either lyse infected liver cells or impede further intracellular parasite development through the localized secretion of appropriate cytokines. Ideally, both types of immune responses (humoral and cell-mediated) should be recalled following further vaccination or upon subsequent natural infection. The vaccine should therefore be capable of inducing appropriate subsets of memory T and B cells, specific for epitopes derived from parasite proteins.