This proposal describes experiments to develop a defined vaccine against schistosomiasis for use in humans. In pursuit of this goal, laboratory animals will be vaccinated with purified antigens, antigen fragments, synthetic peptides, and fusion proteins produced by recombinant DNA technology.
The specific aims of this proposal are: 1) to study via vaccination trials in mice, the protective potential of 3 distinct surface membrane antigens when administered singly or in combination; 2) to test whether fusion proteins which express epitopes found on the 3 surface antigens can induce protective immunity in mice; 3) to map the epitopes detected by antibodies on the 3 native surface antigens, and then test whether antigen fragments and/or synthetic peptides are immunogenic in vivo; 4) to test if mice become sensitized to eggs and egg antigens after vaccination with native, recombinant or synthetic antigens. The three surface membrane antigens were selected with protective monoclonal antibodies produced from mice. All three antigens can be purified by immunoaffinity chromatography and/or electroelution. Epitopes will be mapped using both protective monoclonal antibodies and monospecific antisera as probes. Antigens will be fragmented into peptides by treatment with cyanagen-bromide and other proteases. Antigen fragments will be purified by reverse-phase HPLC, or by electro-elution after SDS-PAGE. Fusion proteins to be tested were produced by recombinant cDNA clones selected from adult worm and cercarial tail cDNA libraries using lambda gtll as expression vector. Assays for sensitization to antigens will be done by both lung and liver granuloma assays.
