CHILDHOOD VACCINES AND DENTAL CARIES IMMUNITY

描述(改编自《调查者摘要》)：一个持续的长期 根据这项拨款进行的研究的目标是开发一种牙科 通过粘膜免疫系统发挥保护作用的龋齿疫苗。这个 变形链球菌的感染模式和最初的人体反应 抗原已经揭示了潜在的时间和特异性参数 儿童龋齿疫苗的应用，并提出了新的建议 疫苗治疗的途径。这项研究的一个直接结果是 变形链球菌葡聚糖结合蛋白(GBP59)的鉴定 新的变形链球菌疫苗治疗靶点。这一发现允许 一种更广泛的基于免疫调节的牙科控制方法 比以前更有可能发生龋齿。一种新型粘膜的初步研究 佐剂和生物粘附性微粒已经提出了新的或更多的 改进的方法，提高对粘膜应用的免疫诱导 抗原，如GBP59。为了建立在这些重要发现的基础上， 研究人员将探索变形链球菌GBP59的分子特征 通过克隆和测序负责其合成的基因。表位 与防龋性相关的，然后使用推导出的 与其他蛋白质的功能重要区域的序列同源性， 并通过使用免疫学探针。这些表位在生物医学中的潜在用途 然后，亚单位疫苗将在啮齿动物龋齿模型中进行测试。另外， 人类T和B淋巴细胞对这些表位的反应性将 被探索。以粘膜为基础的疫苗的成功不仅取决于 关于包含适当的表位，而且还关于诱导 有足够的免疫反应。因此，调查人员建议探索 艰难梭菌毒素A(TXA)作为一种新型毒素的潜力 重要龋病疫苗抗原的粘膜佐剂，如GBP59，AS 以及它对防龋性抗原表位的贡献潜力 可诱导产生抗体。将抗原定向递送到适当的 淋巴部位也有助于黏膜疫苗的成功。 因此，拟议的研究将考察一部小说的能力 生物粘附性微粒系统提供免疫原剂量的这些 GALT和BALT中诱导部位的抗原性构建物，并诱导 保护性免疫反应，单独或与TXA联合使用。

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.