LIPOSOME S MUTANS DELIVERY SYSTEM FOR CARIES IMMUNITY

脂质体已用于靶向药物递送，最近用于药物递送。 使用纯化的可溶性抗原开发口服疫苗 诱导粘膜免疫应答。 尽管这些机制 脂质体促进对可溶性抗原的应答的诱导， 已经清楚地表明，已经表明，这些囊泡，当给予 口服，被M细胞吸收，用于将抗原递送到潜在的 派尔集合淋巴结中的淋巴样细胞，其作为佐剂， 用于分泌性免疫应答的抗原加工。 这项建议会 检查脂质体的特性， 增强对口服S.变形抗原 （血清型C碳水化合物抗原和葡糖基转移酶）。 在这 在这方面，使用透射电子显微镜，在体外实验将 以确定脂质体的物理特性， 脂质体中的抗原定位。 随后的体内研究将评估 脂质体囊泡的命运，因为它们被M细胞吸收，在一个 实验大鼠模型及最佳脂质体/抗原 这种吸收的特点。 利用一只已知的无菌鼠 龋齿模型，抗原/脂质体制剂将评估其 有效诱导保护性免疫反应。 人口腔 还将继续进行免疫研究， 该疫苗输送系统的适用性，并确定 这种疫苗的特性对诱导粘膜免疫反应很重要， 应答 人类志愿者将摄入肠溶胶囊 含有脂质体/抗原制剂的溶液中持续7天。 免疫 将通过分析腮腺唾液、泪液和 血浆用于抗原特异性抗体应答。 此外， 牙菌斑中S.变种人将会 测定 将使用外周血进行ELISPOT分析 淋巴细胞，以检测抗原特异性B细胞向局部淋巴细胞的迁移。 分泌部位 总之，拟议的研究旨在 定义了一种实用且有效的口服脂质体/S。变形抗原 递送系统用于诱导保护性粘膜免疫应答。 这些研究不仅将扩大和扩展我们对 机制参与诱导粘膜免疫对S。 变形杆菌感染，但他们将提高我们的理解的方式， 诱导针对多种其它粘膜病原体的粘膜免疫。

Liposomes have been used in targeted drug delivery and recently in the development of oral vaccines using purified soluble antigens for the induction of mucosal immune responses. Although the mechanisms by which liposomes promote the induction of responses to soluble antigens have not been Clearly shown, it has been suggested that these vesicles, when given orally, are taken up by M cells for delivery of antigen to underlying lymphoid cells in the Peyers patch which serves as an adjuvant for processing of antigen for secretory immune responses. This proposal will examine the characteristics of liposomes that are important in potentiating immune responses to orally administered S. mutans antigens (serotype c carbohydrate antigen and glucosyltransferase). In this regard, using transmission electron microscopy, in vitro experiments will be conducted to determine the physical characteristics of liposomes and antigen location in liposomes. Subsequent in vivo studies will assess the fate of the liposomal vesicles as they are taken up by M cells in an experimental rat model as well as optimum liposome/antigen characteristics for this uptake. Using an established gnotobiotic rat caries model, antigen/liposome preparations will be assessed for their effectiveness in inducing protective immune responses. Human oral immunization studies will also be continued in order to establish the applicability of this vaccine delivery system and to determine the properties of this vaccine important for the induction of mucosal responses. Human volunteers will ingest enteric coated capsules containing liposome/antigen preparations for seven days. Immune responses will be monitored by analysis of parotid saliva, tears and plasma for antigen specific antibody responses. Additionally, changes in levels of colonization of dental plaque with S. mutans will be determined. ELISPOT analysis will be done with peripheral blood lymphocytes to detect the migration of antigen specific B-cells to local secretory sites. In conclusion, the proposed studies are directed at defining a practical and yet effective oral liposome/S. mutans antigen delivery system for the induction of protective mucosal immune responses. Not only will these studies expand and extend our understanding of the mechanisms involved in the induction of mucosal immunity against S. mutans infection, but they will improve our understanding of ways to induce mucosal immunity against the multitude of other mucosal pathogens.