ENHANCING IMMUNOGENICITY OF EPITOPE INSERTS IN FLAGELLIN

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1. It has been shown that the hypervariable region of flagellin of strains of Salmonella (potentially useful as typhoid vaccines) is a suitable locus for insertion of DNA coding for epitopes which are of interest as potentially effective immunogens for diseases other than salmonellosis. A nonapeptide which represents aa163-171 of Il-1 beta has been shown to be immunoenhancing. We shall test whether the expression of this nonapeptide enhances immune response to determinants which are juxtaposed to, near or spatially removed from this nonapeptide when it is inserted in the hypervariable region of vaccine strains of Salmonella. 2. Many polysaccharide antigens are considered to bc T independent in the sense that response to them does not require T cell help; anamnestic responses are not elicited and the immunoglobulin isotype response is restricted with such antigens. We propose to test a method to convert oligosaccharide determinants of such antigens to T dependence enabling both the elicitation of memory and unrestricted class switching. Furthermore, the process would make it possible to have such antigens expressed as peptide surrogates as piggy-back antigens in the hypervariable region of flagellin as in 1. A monoclonal anti Salmonella Vi will be used to screen a random peptide library for adventitious cross-reactive peptides which will be back-translated to DNA, and inserted for expression in the hypervariable region of flagellin. The essential hypothesis is that cross-reactivity as recognized in reaction will bc matched by cross-reactivity in induction of immune response. Specifically this might greatly enhance the utility of the typhoid vaccines being tested since they do not at present elicit anti-Vi.