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: 6951900
• 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 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6951900
• 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） 尽管对龋齿发病机制有相当多的了解，但这种传染性传染病仍然是一个世界性的公共卫生问题，主要影响遭受变形链球菌挑战的人群。尽管使用氟化物具有有益效果，但不良的口腔卫生和高蔗糖消耗继续促进早期变形链球菌感染和疾病。龋齿疫苗的临床前研究已成功干扰变形链球菌感染和疾病。这种方法需要一定水平的分泌性免疫成熟度，足以在感染前对这些疫苗中包含的毒力抗原产生充分的反应。通常受到变形链球菌攻击的儿童在 18-36 个月大时会受到感染，并形成针对几种变形链球菌抗原的唾液 IgA 抗体。然而，人们对这些抗原的分泌性免疫反应知之甚少，这些儿童由于严重的挑战而更早地被定植。为此，NIDCR 要求研究变形链球菌的适应性免疫、感染程度和龋齿发展之间的关系。我们提出了一项前瞻性研究，以调查在遭受严重变形链球菌感染挑战的人群中，在变形链球菌最初口服建立期间，IgA抗体对初始定殖者（轻链球菌）和致病菌（变形链球菌）的反应。将对 160 名 6-12m 至 24-30m 的儿童进行跟踪，间隔为 6m。临床检查后将在每个时间间隔进行微生物学检查，以分析轻链球菌和变形链球菌的感染水平。将测量变形链球菌克隆的遗传多样性和稳定性。将收集唾液样本以测量 IgA 总水平和轻链球菌/S 的 IgA 抗体水平。变形链球菌分泌/表面相关抗原。将比较这些链球菌菌株的 IgA 反应模式和程度，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和龋齿发展的时间和强度对这些数据进行分析。这些研究应有助于确定针对龋齿高危儿童的疫苗方法。

项目成果

Transcriptional analysis of gtfB, gtfC, and gbpB and their putative response regulators in several isolates of Streptococcus mutans.

• DOI: 10.1111/j.1399-302x.2008.00451.x
• 发表时间: 2008-12
• 期刊: Oral microbiology and immunology
• 作者: R. N. Stipp;R. Gonçalves;J. F. Höfling;Daniel J. Smith;R. MATTOS-GRANER

CovR and VicRK regulate cell surface biogenesis genes required for biofilm formation in Streptococcus mutans.

• DOI: 10.1371/journal.pone.0058271
• 发表时间: 2013
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Stipp RN;Boisvert H;Smith DJ;Höfling JF;Duncan MJ;Mattos-Graner RO
• 通讯作者: Mattos-Graner RO

Age-specific salivary immunoglobulin A response to Streptococcus mutans GbpB.

年龄特异性唾液免疫球蛋白 A 对变形链球菌 GbpB 的反应。

• DOI: 10.1128/cvi.00098-07
• 发表时间: 2007
• 期刊: Clinical and vaccine immunology : CVI
• 作者: Nogueira,RucheleD;Alves,AlessandraC;King,WilliamF;Goncalves,ReginaldoB;Hofling,JoseF;Smith,DanielJ;Mattos-Graner,RenataO
• 通讯作者: Mattos-Graner,RenataO