The general objective of the current proposal is to exploit DNA vaccination as a treatment modality for chronic inflammatory diseases including autoimmune diseases and tuberculosis. It is increasingly realized that protective immunity against infectious diseases depends on immune recognition of 'altered self'. Many of the prominent microbial antigens seen in infection are now known to be highly conserved or homologous with mammalian protein antigens. Using DNA vaccination it has been demonstrated in an animal model that at least three mycobacterial antigens can be protective against tuberculosis infection. Two of these mycobacterial antigens are highly conserved heat shock proteins known to be cross-reactive with the mammalian homolgues. One of them, hsp650, is implicated and extensively studied in the aetiology of autoimmune arthritis, diabetes and a variety of other diseases with a presumed autoimmune component. Hence this antigen presents an ideal model to test ways of manipulating DNA vaccines to selectively favor the development of either anti-autoimmune or antimicrobial responses or both. In this project we propose to develop a transdisease vaccination technology for the treatment of chronic inflammatory conditions. To meet the overall objective of this research project, we propose to execute a research plan that can roughly be divided in three tasks, each with a measurable objective.