Designer vaccines for parasitic diseases

Abstract

Conventional ways of developing vaccines against infections, either on pragmatic grounds or by identifying protective antigens and attempting to mimic natural immune responses, have largely been unsuccessful for parasitic-infections, mainly because of the complexity of the immunological processes involved. It is clear that a new approach is required and it is now known that the "immunological environment" in which the immune response is initiated is as, or more, important than the actual antigens used. CD4+ and CD8+ T1 cells, through the agency of IL-2 and IFN-gamma, direct the response towards cell-mediated immunity involving cytotoxicity and macrophage activation, whereas T2 cells, through the agency of IL-4 and IL-10, direct the response towards antibody production. The two poles are counter-regulatory in that IFN-gamma inhibits antibody formation and IL-4 and IL-10 inhibit macrophage activation. However, immune responses are not immutable and can be artificially driven towards one or other pole, for example IFN-gamma, IL-2 and IL-12 favour T1 responses, whereas IL-4 and IL-10 favour the T2 type. With this knowledge, it is possible to design recombinant or nucleic acid vaccines that include gene products or genes for desirable cytokines as well as the appropriate antigen. For example, in experimental leishmaniasis, protective immune responses can be induced by the incorporation of genes for IL-2 and IFN-gamma into recombinant Salmonella typhimurium vectors and nucleic acid vaccines. A similar approach might be appropriate in experimental schistosomiasis, in which exogenous IL-12 drives the immune response towards the T1 pole and ameliorates T2-mediated pathology. These approaches require novel delivery systems and these have already begun to produce encouraging results. However, simply modifying the nature and route of administration of the vaccine is not enough and attention has now turned to the effector molecules involved, for example nitric oxide, and the signaling systems that are modified by the presence of particular cytokines.