MUCOSAL IMMUNIZATION USING AN H PYLORI UREASE

目前，微粒作为用于治疗癌症的载体的实际给药是困难的。 口服疫苗制剂的提供由于穷人而受到限制， 通过胃肠道进行颗粒采样的效率。 添加 对疫苗载体的生物粘附特性可以增加免疫的效率。 从而减少达到有效剂量所需的剂量 预防针 据信，容易结合的免疫原性分子 肠道上皮细胞表面刺激更强的免疫力 反应比非粘附分子。 这很可能是由于增强 通过覆盖肠淋巴的M细胞采集粘附免疫原 滤泡，专门用于抗原采样和运输， 粘膜抗体诱导位点。 在初步研究中， 研究了各种生物粘附化合物增强 聚（乳酸-羟基乙酸）（PLGA）的结合和取样 在小鼠Peyer集合淋巴结（PP）组织中的微粒。 我们现在有一个 定量工具，将颗粒摄取的优化与 免疫反应的发展。 拟议的第一阶段项目现在将直接比较这些改进 在颗粒摄取与免疫原性，以定量确定 摄取与免疫力发展之间的相关性。 他们提出 这项工作使用了一种针对幽门螺杆菌的候选疫苗抗原， 是消化性溃疡病和慢性（B型）的主要病例 胃炎，并已强烈牵连的共同因素的成因， 胃癌 这些策略是根据这种特征鲜明的 该系统也可以潜在地应用于其他抗原。 拟议的商业应用：疫苗载体的开发， 口服给药对疫苗技术提出了重大挑战。 口服免疫是一种更方便、更安全的免疫方式，而粘膜免疫 更有效地引发分泌性免疫反应。 许多疫苗 制造商将成为潜在的商业市场， 开发/利用这项技术。

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.