The overall goal of this research is to develop a vaccine against schistosomiasis using novel approaches based on anti-idiotype antibodies and synthetic peptide synthesis. The concept for these studies on the function, structure and therapeutic use of 'Idiotope Vaccines' is based on the Immune Network Theory which predicts the existence of so-called 'Internal Antigens'. Experimental support for 'Internal Antigen' derived vaccines has been recently obtained by one of us (HK) by inducing PC anti-streptococcal immunity using a modified anti-idiotypic hybridoma. In the murine model of schistosomiasis, we will identify anti-idiotype antibodies (internal antigens) and demonstrate their protective value against infection. Then to make this applicable to humans we will identify the internal antigen epitopes. This will be accomplished by deducing the amino acid sequence of the variable regions of internal image anti-idiotypes by primer extension sequencing of mRNA. Idiotopic regions expressing the internal antigen will then be identified by computer modeling. Computer modeling studies will indicate the synthetic peptides to be made. By immunizing mice with the synthesized idiotope peptide-protein complex and subsequently challenging them with Schistosoma we will demonstrate the feasibility of making a synthetic idiotope vaccine. These studies will lay the ground work for specific vaccines against the human schistosomes.
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