Schistosomiasis is a chronic, often debilitating, disease afflicting over 200 million people, an additional 600 million are at risk in 74 countries. Although schistosomicidal agents and other control measures, including public hygiene and snail control exist, the advent of an efficacious vaccine still remains the most potentially powerful means for control of this disease. Schistosomes interact closely with their host, performing functions such as nutrient uptake, immune avoidance and attachment. Our goal is to test the hypothesis that host-exposed, schistosome proteins that undertake such essential functions can be effective targets of a schistosomiasis vaccine. In this proposal, we focus on one host interactive protein and utilize the latest technologies to stimulate and modulate immune responses so as to definitively test the hypothesis that these proteins will be effective targets of a highly protective schistosomiasis vaccine. Our vaccine candidate is calcium activated neutral protease (= calpain, =sm-p80), which plays a pivotal role in the surface membrane renewal of schistosomes, a phenomenon which is considered to be a mechanism employed by hemo-helminths to evade host immunity. The protein has been shown to be exposed at the host parasite interface and to be naturally immunogenic. Therefore if an immune response is induced against this protein, it should cause substantial harm to the worm. In this application we propose to construct expression vectors containing cDNA encoding calpain and cytokines for DNA immunization. We will test DNA immunization protocols using these constructs containing calpain and also vectors directing co-expression of cytokines to enhance immune recognition of calpain for its ability to elicit a damaging effect on the survival of schistosomes. In addition to testing the hypothesis that functionally important schistosome host interactive proteins make effective vaccine targets, the results of the proposed experiments should offer additional benefits. Our studies will provide new data on how these strategies and cytokines succeed in modifying immune responses to amphitropic proteins. Of greater importance, these studies should provide new insight into immune mechanisms which can damage worm parasites and establish a model by which to subsequently study the effector mechanisms.
