The immunological challenge to developing a vaccine to the blood stages of malaria parasites

Twenty-one years after malaria antigens were first cloned, a vaccine still appears to be a long way off. There have been periods of great excitement, and in model systems, subunit vaccine homologs can induce robust protection. However, significant challenges exist concerning antigenic variation and polymorphism, immunological non-responsiveness to individual vaccine antigens, parasite-induced apoptosis of immune effector and memory cells, and immune deviation as a result of maternal immunity and alterations of dendritic cell function. Novel approaches will be required. This review addresses some of the approaches that might present malaria antigens in a way designed to induce superior immune responses or that target novel conserved epitopes. Cell-mediated immunity, acting independently of antibody, may exert potent anti-parasite effects, and identification of multiple target antigens/epitopes could lead to the development of vaccines with profound efficacy.