Muscosal Immunity in Heavily S. Mutans Exposed Children

描述（由申请人提供） 尽管对龋齿的发病机制有相当多的了解，但这种传染性疾病仍然是一个世界性的公共卫生问题，主要影响变形链球菌高挑战下的人群。虽然使用氟化物有有益的效果，但不良的口腔卫生和高蔗糖消耗继续促进早期S。变形菌感染和疾病。龋齿疫苗的临床前研究已经成功地干扰了S。变形菌感染和疾病。这种方法需要足够的分泌性免疫成熟度水平，以在感染前对这些疫苗中含有的毒力抗原产生足够的应答。儿童通常挑战S。变形链球菌在18-36月龄之间感染，并形成唾液伊加抗体，以对抗几种变形链球菌。变形抗原然而，很少了解的是这些抗原的分泌性免疫反应的儿童成为殖民地早得多，由于沉重的挑战。为此，NIDCR要求研究获得性免疫与S。变形菌、感染程度和龋齿发展。我们提出了一项前瞻性研究，以调查伊加抗体反应的初始殖民者（S。缓症）和致病菌（S.在S. mutans口腔建立初期，变形链球菌在经历重S.变形杆菌感染性挑战将对160名6- 12 m至24- 30 m年龄的儿童以6 m间隔进行随访。临床检查后将在每个时间间隔进行微生物检查，以分析S. mitis和S.变异人研究表明，S.将测量变异克隆。将采集唾液样本，以测量伊加总水平和抗链球菌伊加抗体水平。缓生S.变形杆菌分泌/表面相关抗原。将比较对这些链球菌菌株的伊加应答的模式和程度，以评估分泌性免疫应答的相对成熟度。然后将这些数据与S的时间和强度进行分析。变形菌感染和龋齿的发展。这些研究应有助于确定针对龋齿高危儿童的疫苗方法。

DESCRIPTION (provided by applicant) Despite considerable knowledge of dental caries pathogenesis, this transmissible infectious disease is still a worldwide public health problem, affecting mainly populations under high Streptococcus mutans challenge. Although use of fluoride has beneficial effect, poor oral hygiene and high sucrose consumption continue to promote early S. mutans infection and disease. Preclinical studies with dental caries vaccines have successfully interfered with S. mutans infection and disease. This approach requires a level of secretory immune maturity sufficient for adequate response to virulence antigen(s) contained within these vaccines before infection. Children normally challenged with S. mutans become infected between 18-36 months of age and form salivary IgA antibody to several S. mutans antigens. However, poorly understood are secretory immune responses to these antigens in children who become colonized much earlier due to heavy challenge. To this end, the NIDCR has requested studies of the relationships of adaptive immunity to S. mutans, degree of infection, and caries development. We propose a prospective study to investigate IgA antibody responses to initial colonizers (S. mitis) and pathogenic bacteria (S. mutans) during the period of initial oral establishment of S. mutans in a population undergoing heavy S. mutans infectious challenge. 160 children will be followed at 6m intervals from 6-12m until 24-30m of age. Clinical examinations will be followed by microbiological exams at each interval to analyze levels of infection by S. mitis and S. mutans. The genetic diversity and stability of S. mutans clones will be measured. Salivary samples will be collected to measure total levels of IgA and levels of IgA antibody to S. mitis/S. mutans secreted/surface-associated antigens. Patterns and extent of IgA responses to these streptococcal strains will be compared to assess relative maturation of secretory immune responses. These data will then be analyzed with respect to the time and intensity of S. mutans infection and development of dental caries. These studies should help to define vaccine approaches targeting children at high risk for dental caries.