This proposal has three major goals, all of which center on the surface of the human parasite Schistsosoma mansoni. First, the cercarial glycocalyx will be analyzed biochemically and immunologically in order to test its suitability as a candidate for a vaccine. The glycocalyx is highly antigenic, reacts with a protective mnonoclonal antibody, and is a mildly acidic glycoprotein that is over half carbohydrate. The glycocalyx will be purified, analyzed, fragmented and both the intact molecule and fragments will be tested for their ability to protect mice from schistosome infections. A second goal is to determine how the parasite protects itself from attack by cells of the host's immune system. In particular, the parasite lyses human granulocytes and acquires host membrane components. The mechanism of lysis will be explored with fluorescence photobleaching recovery techniques and the mechanism of host antigen acquisition with electron microscopic immunocytoochemnistry and freeze fracture. If these mechanism can be determined, the phenomena may be inhibited therapeutically with a resulting decrease in infection. Finally, since the surface of the parasite is syncytium covered by two lipid bilayers, the outer of which appears to contain very little protein, the lipid composition and biosynthesis of the surface will be examined by radiolabeling and HPLC. Many properties of the parasite surface can be attributed potentially to its lipids. Knowledge of the lipid makeup and turnover of the surface membranes may lead to the ability to produce biochemical alterations in these membranes which make the worm susceptible to immune killing.
Showing the most recent 10 out of 36 publications