CHILDHOOD VACCINES AND DENTAL CARIES IMMUNITY

根据DE-06153进行的研究的主要长期目标是 开发一种龋齿疫苗， 粘膜免疫系统。 必然的长期目标， 实现这一目标是（a）确定粘膜免疫的年龄 机制已经足够成熟，可以表现出潜在的保护作用， 免疫应答，（B）鉴定突变链球菌组分， 具有足够的免疫原性以引发潜在的保护性免疫 在用致龋植物群定殖之前的反应，和（c）对 评估小涎腺内免疫成分的能力 组织作为潜在防龋的诱导部位， 口腔内的抗体形成。 虽然这些长期 目标是针对龋病免疫，由此产生的研究 应该可以增强许多感染性 通过粘膜途径侵入的疾病。 本申请中描述的研究旨在首先揭示 分泌免疫的能力在一个年龄，这是相关的， 最初链球菌感染。 第二，抗原关系 和两种新型突变链球菌的保护性免疫潜力 初始时具有免疫原性的成分（GBP抗原） 将鉴定突变链球菌感染。 第三，能力 不同的小唾液腺隔间，以显示分泌 用明矾相关和 将测量微囊化破伤风类毒素。 将通过以下具体努力探索这些目标： 目的：（1）分析幼儿对 蛋白质组分（破伤风类毒素）、多糖结合物 （流感嗜血杆菌B荚膜多糖），细胞 （百日咳杆菌）或完整减毒病毒疫苗（脊髓灰质炎病毒） 在突变的关键期之前立即施用 链球菌的感染性;（2）测定 变形链球菌59 kDa葡聚糖结合蛋白（GBP）引发免疫 干扰细菌定植和致龋性的反应 大鼠龋齿模型中的变形链球菌;（3）纯化， 表位特异性的评估，以及诱导 保护性免疫反应的变形链球菌抗原（ 最常见的唾液免疫反应是 在MS感染的初始阶段检测到）;和（4）分析 局部免疫的小唾液腺方面， 唾液反应在不同小腺体内的分布 微环境（下唇，上唇和腭）与明矾相关 和微囊化破伤风类毒素，用作蛋白质的类似物， 的龋齿疫苗。

A principal long-term goal of the research conducted under DE-06153 is to develop a dental caries vaccine that mediates protection via the mucosal immune system. Corollary long-term objectives necessary to achieve this goal are (a) determine the age at which mucosal immune mechanisms are sufficiently mature to manifest potentially protective immune responses, (b) to identify mutants streptococcal components that are sufficiently immunogenic to elicit potentially protective immune responses prior to colonization with a cariogenic flora, and (c) to evaluate the capacity of immune elements within minor salivary gland tissue to function as inductive sites for potentially caries-protective antibody formation within the oral cavity. Although these long-term objectives are targeted for caries immunity, the resulting research should permit enhancement of secretory immunity for many infectious diseases that invade via mucosal routes. The research described in this application is intended first to reveal the capacity for secretory immunity at an age that is correlated with initial streptococcal infection. Secondly, the antigenic relationships and potential for protective immunity of two novel mutants streptococcal components (GBP Antigen) that are immunogenic at the time of initial mutants streptococcal infection will be identified. Thirdly, the ability of different minor salivary gland compartments to manifest secretory immune response after local induction with alum-associated and microencapsulated tetanus toxoid will be measured. These objectives will be explored by pursuing the following specific aims: (1) analysis of secretory immune responses of young children to components of proteins (tetanus toxoid), polysaccharide conjugate (capsular polysaccharide of Haemophilus influenza b), cellular (Bordetella pertussis), or intact attenuated viral vaccines (poliovirus) administered immediately prior to the critical period of mutans streptococcal infectivity; (2) determination of the ability of Streptococcus mutans 59 kDa glucan binding protein (GBP) to elicit immune responses that interfere with the colonization and cariogenicity of mutans streptococci in a rat model of dental caries; (3) purification, evaluation of epitopic distinctiveness, and potential for induction of protective immune responses by mutans streptococcal Antigen (the component to which the most frequent salivary immune responses are detected during the initial period of MS infectivity); and (4) analysis of topical immunization of minor salivary glands with respect to distribution of salivary responses within different minor gland microenvironments (lower, upper labial and palatine) with alum-associated and microencapsulated tetanus toxoid, used as an analogue of a protein- based dental caries vaccine.