The aim of this project is to study mechanisms of immunity and immune evasion in schistosomiasis with the ultimate goal of developing an experimental vaccine employing defined antigens: A. Genetics of protective immunity in the irradiated vaccine model. A single gene defect was identified by means of genetic crosses which controls the deficient irradiated vaccine induced immunity of A/J mice. Using recombinant inbred strains the gene was tentatively mapped to chromosome 6 of the mouse. Genetic complementation experiments revealed that the gene locus controlling the A/J mouse immune defect is distinct from that controlling the deficient immunity of P mice. B. Mechanisms of immune evasion of developing schistosomula. Schistosomula developing in vitro were shown to become resistant to killing by activated macrophages. This phenomenon was temporally correllated with a change in membrane permeability to the probe tetraphenylphosphonium. Susceptibility to activated macrophage killing was shown to be regained in 2 1/2 week old worms but lost in older parasites suggesting that 2 1/2 week old schistosomes may be a target for late stage immunity. C. Identification of vaccine immunogen. A 97 Kd soluble schistosome protein was identified as the sole antigen recognized by antibodies from mice vaccinated with BCG plus shcistosome extracts. Antigen purification and vaccination experiments supported the hypothesis that this molecule is the immunogen responsible for the induction of protective immunity in the BCG model.
