CHILDHOOD VACCINES AND DENTAL CARIES IMMUNITY

描述（改编自研究者摘要）：一项持续的长期研究 根据这项赠款进行的研究的目标是开发一种牙科 通过粘膜免疫系统介导保护作用的龋齿疫苗。 的 变形链球菌感染模式和人类初始反应 抗原揭示了潜在的时间和特异性参数 儿童龋齿疫苗的应用，并提出了新的 疫苗治疗的途径。 这项研究的直接结果是， 鉴定变形链球菌葡聚糖结合蛋白（GBP59）作为 疫苗治疗的新变异链球菌靶点。 这一发现使得 一种基础更广泛的免疫介导的牙科控制方法， 比以前可能的龋齿。 新粘膜的初步研究 佐剂和生物粘附微粒已经提出了新的或更多的 改进的，增强粘膜应用免疫诱导的方法 例如GBP59抗原。 在这些重要发现的基础上， 研究人员将探索S.变形菌GBP59 通过克隆和测序负责其合成的基因。 表位 与龋齿保护相关的，然后将使用推导的 与其它蛋白质的功能重要区域的序列同源性， 和使用免疫探针。 这些表位的潜在用途， 然后在啮齿动物龋齿模型中测试亚单位疫苗。 还 人T和B淋巴细胞对这些表位的反应性的存在将 被探索。 粘膜疫苗的成功不仅取决于 包括适当的表位，但也对诱导的能力， 足够的免疫反应。 因此，研究人员建议探索 艰难梭菌毒素A（TxA）作为一种新的 重要龋齿疫苗抗原的粘膜佐剂，如GBP59， 以及其贡献表位的潜力， 可以诱导抗体。 将抗原靶向递送至适当的 淋巴部位也有助于粘膜疫苗的成功。 因此，拟议的研究将调查小说的能力， 生物粘附性微粒系统，以递送免疫原性剂量的这些 将抗原构建体与GALT和BALT中的诱导位点结合，并诱导 保护性免疫应答，单独和与TxA组合。

DESCRIPTION (Adapted from investigator's Abstract): A continuing long-term goal of the research conducted under this grant is to develop a dental caries vaccine that mediates protection via the mucosal immune system. The patterns of infection and initial human responses to mutans streptococcal antigens have revealed parameters of time and specificity for potential pediatric application of dental caries vaccines, and have suggested novel pathways for vaccine therapy. A direct result of this study has been the identification of Streptococcus mutans glucan binding protein (GBP59) as a new mutans streptococcal target for vaccine therapy. This discovery permits a broader based approach to immunologically mediated control of dental caries than previously possible. Preliminary studies with novel mucosal adjuvants and bioadhesive microparticles have suggested new, or more refined, methods of enhancing the induction of immunity to mucosally applied antigens such as GBP59. To build on these important discoveries, the investigators will explore the molecular characteristics of S. mutans GBP59 by cloning and sequencing the gene responsible for its synthesis. Epitopes associated with caries protection will then be identified using deduced sequence homologies with functionally important regions of other proteins, and by using immunologic probes. The potential use of these epitopes in subunit vaccines will then be tested in a rodent caries model. Also, the presence of human T and B Iymphocyte responsiveness to these epitopes will be explored. The success of mucosal-based vaccines is dependent, not only on inclusion of appropriate epitopes, but also on the ability to induce an adequate immune response. Thus, the investigators propose to explore the potential for Clostridium difficile toxin A (TxA) to serve as a novel mucosal adjuvant for important caries vaccine antigens, such as GBP59, as well as its potential to contribute epitopes to which caries-protective antibody may be induced. Targeted delivery of antigen to appropriate lymphatic sites can also contribute to the success of mucosal vaccines. Hence, the proposed studies will investigate the ability of a novel bioadhesive microparticle system to deliver immunogenic doses of these antigenic constructs to inductive sites in the GALT and BALT, and to induce protective immune responses, alone, and in combination with TxA.