| The development of novel vaccines for bovine mycobacterial diseases would likely reduce the incidence of bovine tuberculosis and Johne's disease. Chapters 2 and 3 describe the development and testing of subunit vaccines for both bovine tuberculosis and Johne's disease in cattle, the natural host. Both vaccines consisted of mycobacterial culture filtrate proteins (CFP), recombinant interleukin 2 (IL-2), and adjuvants. Animals were vaccinated subcutaneously and challenged with either a virulent strain of M. bovis or M. a. paratuberculosis. The bovine tuberculosis CFP vaccine did not interfere with the tuberculin skin test and significantly reduced the severity of lung lesions seen post challenge. Unfortunately, it also significantly increased the dissemination of M. bovis. The Johne's disease CFP vaccine trial has yet to be concluded however, preliminary evidence suggests that the CFP vaccine induced significantly higher percentages of αβ and γδ T cells with activated phenotypes than the adjuvants alone. The protective efficacy of the vaccine and the biological relevance of the activated T cell populations will be conclusively determined at the end of the study.; In addition to the bovine vaccine trials, this study examined phenotypic and functional characteristics of bovine γδ T cells, Chapters 4 and 5. This study identified and characterized the expression of activation markers on two peripheral blood populations of bovine γδ T cells. CD62L, CD44, and CD45R were identified as useful markers of activation on WC1+ and WC1− γδ T cells. This study also demonstrated the propensity of bovine γδ T cells to expand in response to stimulation with various mycobacterial antigens. In addition, bovine γδ T cells were identified as potent producers of IFN-γ, following stimulation with a component of the mycobacterial cell wall, mycolylarabinogalactan peptidoglycan (mAGP). Given that the bovine tuberculosis and Johne's disease subunit vaccines described in this study failed to induce significant amounts of IFN-γ following vaccination, mAGP may be a useful adjuvant component of future CFP based vaccines for bovine mycobacterial diseases. |
