MUCOSAL IMMUNIZATION USING AN H PYLORI UREASE

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Currently, the practical administration of miroparticles as carriers for the delivery of oral vaccine preparations is limited due to the poor efficiency of particle sampling by the GI tract. The addition of bioadhesive properties to vaccine carriers may increase the efficiency of sampling thereby reducing the doses required to achieve effective vaccination. It is believed that immunogenic molecules which readily bind to the surface of gut epithelial cells stimulate a stronger immune response than non-adherent molecules. This is likely due to enhanced sampling of adherent immunogens by M cells overlying intestinal lymphoid follicles, which ar specialized for antigen sampling and transport to mucosal antibody inductive sites. In preliminary studies, we have examined the ability of various bioadhesive compounds to enhance the binding and sampling of poly(lactic-co-glycolic) acid (PLGA) microparticles in mouse Peyer's patch (PP) tissue. We now have a quantitative tool to correlate optimization of particle uptake with the development of an immune response. The proposed Phase I project will now directly compare these improvements in particle uptake with immunogenicity to quantitatively determine the correlation between uptake and th development of immunity. They proposed work uses a candidate vaccine antigen against Helicobacter pylori, which is the principal case of peptic ulcer disease and chronic (type B) gastritis, and has been strongly implicated as co-factor in the genesis of gastric cancer. The strategies developed with this well-characterized system can potentially be applied to other antigens, as well. PROPOSED COMMERCIAL APPLICATION: The development of vaccine carriers for oral delivery presents a significant challenge for vaccine technology. Oral immunization is a more convenient and safer, and mucosal immunization is more efficient for eliciting secretory immune responses. Many vaccine manufacturers would be a potential commercial market for development/utilization of this technology.