CHILDHOOD VACCINES AND DENTAL CARIES IMMUNITY

在DE-06153下进行的研究的一个主要长期目标是 开发一种龋齿疫苗，通过 粘膜免疫系统。必然需要的长期目标 实现这一目标的目标是(A)确定黏膜免疫的年龄 机制已经足够成熟，足以表现出潜在的保护性 免疫反应，(B)鉴定突变链球菌成分， 具有足够的免疫原性以诱导潜在的保护性免疫 在殖民之前对致龋菌群的反应，以及(C)对 评价小涎腺内免疫成分的能力 组织作为潜在防龋剂的诱导部位发挥作用 在口腔内形成抗体。尽管这些长期的 目标是针对龋齿免疫，由此产生的研究 应允许增强对许多传染性疾病的分泌免疫 通过粘膜途径入侵的疾病。 本申请中描述的研究首先旨在揭示 与年龄相关的分泌性免疫能力 最初的链球菌感染。第二，抗原性关系 两个新的链球菌突变体的保护性免疫潜力 初始时具有免疫原性的成分(GBP抗原) 将确定链球菌感染的突变株。第三，能力 不同的小唾液腺隔间，以显示分泌 明矾联合免疫球蛋白局部诱导后的免疫应答 微囊化破伤风类毒素将被测量。 将通过追求以下具体目标来探索这些目标 目的：(1)分析幼儿的分泌性免疫反应。 蛋白质成分(破伤风类毒素)、多糖结合物 (乙型流感嗜血杆菌荚膜多糖)，细胞 (百日咳杆菌)，或完整减毒病毒疫苗(脊髓灰质炎病毒) 紧接在变种的关键时期之前给药 链球菌传染性；(2)链球菌感染能力的测定 变形链球菌59 kDa葡聚糖结合蛋白(GBP)诱导免疫 干扰其定殖性和致龋性的反应 大鼠龋齿模型中的变形链球菌；(3)纯化， 表位特异性的评估，以及诱导的潜力 变形链球菌抗原的保护性免疫反应 唾液免疫反应最频繁的成分 在MS传染性初期检测)；以及(4)分析 关于小涎腺局部免疫的研究 唾液反应在不同小腺体内的分布 与明矾相关的微环境(下、上唇和腭部) 以及微囊化破伤风类毒素，用作蛋白质的类似物- 以龋齿为基础的疫苗。

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.