LIPOSOME-S MUTANS DELIVERY SYSTEM FOR CARIES IMMUNITY

用于龋齿免疫的脂质体-S UTANS 递送系统

• 批准号: 3462364
• 负责人: NOEL K CHILDERS
• 金额: $ 9.63万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-08-01 至 1997-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3462364
• 关键词: B lymphocyte; Peyer's patches; Streptococcus mutans; antigen presentation; antiserum; bacterial antigens; biomaterial development /preparation; carbohydrates; cell migration; dental caries vaccine; dental plaque; disease /disorder model; drug delivery systems; enzyme linked immunosorbent assay; epithelium; germ free condition; guinea pigs; human subject; humoral immunity; immunization; laboratory rabbit; laboratory rat; liposomes; oral administration; oral mucosa; saliva; secretory immune system; serotyping; tear; transmission electron microscopy

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.

脂质体已被用于靶向给药，最近还被用于 利用纯化的可溶性抗原研制猪传染性支原体口服疫苗 诱导粘膜免疫反应。尽管通过这些机制 脂质体促进对可溶性抗原的反应尚未诱导 已经清楚地表明，当给予这些囊泡时， 口服，由M细胞摄取，将抗原输送到底层 作为佐剂的Peyers斑内的淋巴样细胞 针对分泌性免疫反应的抗原处理。这项提议将 检查脂质体的特性，这些特性在 增强口服变形链球菌抗原的免疫应答 (血清型碳水化合物抗原和葡萄糖基转移酶)。在这 在这方面，使用透射电子显微镜，体外实验将 用来测定脂质体的物理特性和 脂质体中的抗原定位。后续的体内研究将评估 脂质体囊泡被M细胞摄取后的命运 实验大鼠模型及最佳脂质体/抗原 这种理解的特征。使用已建立的灵生大鼠 将对龋病模型、抗原/脂质体制剂进行评估 在诱导保护性免疫反应方面的有效性。人类口腔 免疫接种研究也将继续进行，以建立 该疫苗递送系统的适用性，并确定 该疫苗的特性对粘膜诱导具有重要意义 回应。人体志愿者将摄入肠溶胶囊 含脂质体/抗原制剂7天。免疫 反应将通过分析腮腺唾液、泪水和 用于抗原特异性抗体反应的血浆。此外，中的更改 变形链球菌对牙菌斑的定植水平将为 下定决心。ELISPOT分析将用外周血进行 淋巴细胞检测抗原特异性B细胞向局部的迁移 分泌性网站。总括而言，拟议研究的目标是 确定一种实用而有效的口服脂质体/变形链球菌抗原 诱导保护性粘膜免疫反应的递送系统。 这些研究不仅将扩大和扩大我们对 诱导粘膜免疫抗S。 变种人感染，但它们将提高我们对如何 诱导黏膜免疫，对抗多种其他黏膜病原体。