Muscosal Immunity in Heavily S. Mutans Exposed Children

描述(由申请人提供) 尽管人们对龋病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，主要影响高变形链球菌挑战下的人群。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变形链球菌的早期感染和疾病。龋齿疫苗的临床前研究已经成功地干预了变形链球菌的感染和疾病。这种方法需要足够的分泌性免疫成熟水平，足以在感染前对这些疫苗中包含的毒力抗原(S)做出足够的反应。通常患有变形链球菌的儿童会在18-36个月大的时候被感染，并形成对几种变形链球菌抗原的唾液IgA抗体。然而，由于严重的挑战，儿童很早就开始定居，对这些抗原的分泌性免疫反应知之甚少。为此，NIDCR要求研究适应性免疫与变形链球菌、感染程度和龋齿发展的关系。我们提出了一项前瞻性研究，在经历严重变形链球菌感染挑战的人群中，研究在变形链球菌最初口腔建立期间对初始定殖者(米蒂斯链球菌)和病原菌(变形链球菌)的IgA抗体反应。从6-12米到24-30米，每隔6米对160名儿童进行跟踪调查。在临床检查之后，将在每个间隔进行微生物检查，以分析米蒂斯链球菌和变形链球菌的感染水平。将对变形链球菌克隆的遗传多样性和稳定性进行测量。将采集唾液样本，以测量总IgA水平和对变形链球菌分泌/表面相关抗原的IgA抗体水平。将比较对这些链球菌菌株的IgA反应的模式和程度，以评估分泌性免疫反应的相对成熟度。然后将根据变形链球菌感染的时间和强度以及龋齿的发展对这些数据进行分析。这些研究应该有助于确定针对患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.