Muscosal Immunity in Heavily S. Mutans Exposed Children

严重变形链球菌暴露儿童的粘膜免疫

• 批准号: 6830333
• 负责人: Daniel James Smith
• 金额: $ 4.86万
• 依托单位: ADA FORSYTH INSTITUTE, INC.
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-01 至 2006-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6830333
• 关键词: SDS polyacrylamide gel electrophoresis; Streptococcus mitis; Streptococcus mutans; antigen antibody reaction; clinical research; dental caries vaccine; enzyme linked immunosorbent assay; human subject; immune response; immunoglobulin A; mucosal immunity; oral bacteria; polymerase chain reaction; preschool child (1-5); saliva; vaccine development; vaccine evaluation; virulence; western blottings

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.

描述（由申请人提供） 尽管了解龋齿的发病机理，但这种可传播的传染病仍然是世界范围内的公共卫生问题，主要影响了高链球菌突变体挑战下的主要种群。尽管使用氟化物具有有益的作用，但口腔卫生和高蔗糖消耗量较差，继续促进早期的突变链球菌感染和疾病。龋齿疫苗的临床前研究已成功干扰了链球菌感染和疾病。这种方法需要一定水平的分泌免疫成熟度，足以足以对感染前这些疫苗中包含的毒力抗原的足够反应。通常受到葡萄球菌挑战的儿童在18-36个月大的年龄之间被感染，并形成了唾液IgA抗体对几种抗原抗原。但是，人们对这些抗原对这些抗原的分泌免疫反应较低，这些儿童因巨大的挑战而早早被殖民。为此，NIDCR要求研究适应性免疫与葡萄链球菌的关系，感染程度和龋齿发育。我们提出了一项前瞻性研究，以研究IgA抗体对初始菌落（S. mitis）和致病细菌（S. mutans）的反应。从6-12m到24-30m的年龄，将以6m的间隔为160个儿童。临床检查将在每个间隔内进行微生物学检查，以分析Mitis和Mutans链球菌的感染水平。将测量链球菌克隆的遗传多样性和稳定性。将收集唾液样品，以测量IgA的总水平和对Mitis/s的IgA抗体水平。突变分泌/表面相关的抗原。将比较IgA对这些链球菌菌株的模式和程度，以评估分泌免疫反应的相对成熟。然后，将对龋齿链球菌感染的时间和强度分析这些数据。这些研究应有助于定义针对龋齿高风险儿童的疫苗方法。