A role for cytokines in potentiation of malaria vaccines through immunological modulation of blood stage infection.

Malaria is the world's major parasitic disease, for which effective control measures are urgently needed. One of the difficulties hindering successful vaccine design against Plasmodium is an incomplete knowledge of antigens eliciting protective immunity, the precise types of immune response for which to aim, and how these can be induced. A greater appreciation of the mechanisms of protective immunity, on the one hand, and of immunopathology, on the other, should provide critical clues to how manipulation of the immune system may best be achieved. We are studying the regulation of the balance between T helper 1 (Th1) and T helper 2 (Th2) CD4+ T lymphocytes in immunity to asexual blood stages of malaria responsible for the pathogenicity of the disease. Protective immunity to the experimental murine malarias Plasmodium chabaudi and Plasmodium yoelii involves both Th1 and Th2 cells, which provide protection by different mechanisms at different times of infection characterised by higher and lower parasite densities, respectively. This model therefore facilitates a clearer understanding of the Th1/Th2 equilibrium that appears central to immunoregulation of all host/pathogen relationships. It also permits a detailed dissection in vivo of the mechanisms of antimalarial immunity. Here, we discuss the present state of malaria vaccine development and our current research to understand the factors involved in the modulation of vaccine-potentiated immunity.