Schistosomiasis is a health problem of major proportions in many of the developing countries of the world. Combined with other community-wide control measures now available, an effective vaccine would have significant impact in limiting this parasitic infection. A great deal of evidence in experimental models support the contention that although immune induction occurs by classical antigen-specific means, actual effector mechanisms, which may be relatively non-antigen specific, play large roles in challenge parasite attrition. In part the work proposed here is designed to better define vaccine candidates which preferentially stimulate T cell responses leading to resistance. Using mice immunized with irradiated Schistosoma mansoni cercariae, advantage will be taken of the technology for immortalizing antigen-reactive T cells, by T cell cloning procedures, to examine T cell reactivity, define relevant antigens, and determine the functional significance of such T cell reactivity. Experiments will also be conducted to examine larvacidal activity of cells isolated from the lungs of immune mice, in hopes of better defining their potential participation in eliminating challenge infections. In addition, some of the parameters for immune induction and effector mechanisms that have been worked out for the S. mansoni model in the mouse will be expanded to include experiments with the related species, S. japonicum. The overall goal of these experiments will be to speed the development of a safe and effective vaccine by better defining the mechanisms leading to resistance to both S. mansoni and S. japonicum.
