HUMORAL IMMUNE RESPONSE TO NATURAL CHLAMYDIAL INFECTION

对自然衣原体感染的体液免疫反应

• 批准号: 6099666
• 负责人: RAPHAEL Paul VISCIDI
• 金额: $ 6.38万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-01 至 1999-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6099666
• 关键词: Chlamydia trachomatis; antibacterial antibody; bacterial antigens; chlamydial disease; complementary DNA; disease /disorder proneness /risk; female; genital secretion; human tissue; humoral immunity; immunoglobulin A; immunoprecipitation; laboratory rabbit; male; membrane proteins; method development; microorganism immunology; monoclonal antibody; neutralizing antibody; polymerase chain reaction; secretory immune system; serology /serodiagnosis; sexually transmitted diseases; synthetic peptide; western blottings

Chlamydia trachomatis is the leading bacterial sexually transmitted disease. An effective vaccine would be one of the best strategies for control of chlamydia. However, efforts to develop a chlamydia vaccine have been unsuccessful so far. Despite these failures, the available epidemiological data suggest that natural chlamydia infection is followed by short-term protective immunity and, on this basis, development of a vaccine should be feasible. The problem at this juncture is to define the nature of the protective response. One of the major difficulties impeding the definition of epitopes that might mediate protection is the lack of well characterized immunological reagents. One goal of this project is to develop assays to identify antibodies to specific chlamydial gene products by using as antigens either labeled proteins translated in vitro from chlamydial genes that have already been cloned and sequenced, or synthetic peptides which are known to represent serovar-specific epitopes on the major outer membrane protein (MOMP). These reagents will be used to characterize anti-chlamydial response in serum and genital secretion. Most previous methods for measuring antigen-specific IgA in body fluids have not used reagents that detect the secretary component of IgA, nor have they been performed in a way that would eliminate interference by IgG which is also found in body fluids. To address this problem, we will develop methods to assay specific SigA in genital secretions by using a mouse monoclonal antibody specific for secretory IgA. To remove IgG, specimens will be immunoprecipitated. The epidemiological investigations have two principal aims. First, we will determine the antibody prevalence to genital strains of C. trachomatis in populations with different risk of prior STD (STD clinic patients, college-age men and women, girls and boys seen in an adolescent medicine clinic, and healthy children). Second, a nested case-control study will be performed in the Baltimore City STD Clinics in order to evaluate serum and local antibody markers as predictors of reduced risk of chlamydial infection. Serum and genital secretions will be collected prospectively on all clinic attendees. Cases (infected women) and controls (a random sample of uninfected women or uninfected women who are known, through contact tracing, to have been exposed to chlamydia) will be identified and the sepciemn bank will be accessed. The antibody reactivity of cases and controls will be compared to identify serovar-specific or species-specific antibodies which are predictors of reduced risk of infection. A better understanding of the contribution of individual chlamydial antigens to the human immune response to chlamydia and identification of serologic markers that correlate with protection against chlamydial infection should assist in vaccine development efforts.

沙眼衣原体是性传播的主要细菌 疾病 一种有效的疫苗将是最好的策略之一， 控制衣原体。 然而，开发衣原体疫苗的努力 目前还没有成功。 尽管有这些失败， 流行病学数据表明，自然衣原体感染后， 通过短期保护性免疫，并在此基础上， 疫苗应该是可行的。 在这个节骨眼上的问题是定义 保护性反应的本质。 的主要困难之一 阻碍可能介导保护的表位的定义是 缺乏良好表征的免疫学试剂。 其中一个目标是 项目是开发检测方法，以确定抗体的具体 衣原体基因产物作为抗原， 从已克隆的衣原体基因体外翻译 和测序，或合成肽，已知代表 主要外膜蛋白（MOMP）上的血清型特异性表位。 这些试剂将用于表征抗衣原体应答， 血清和生殖器分泌物。 大多数以前的测量方法 体液中的抗原特异性伊加尚未使用检测 伊加的分泌成分，也没有以一种 这将消除IgG干扰，IgG也存在于体内， 流体. 为了解决这个问题，我们将开发方法， 用小鼠单克隆抗体检测生殖器分泌物中特异性SigA 特异于分泌型伊加。 为了去除IgG，将 免疫沉淀。 流行病学调查有两个 主要目标。 首先，我们将确定抗体流行率， 生殖系C.不同风险人群中的沙眼 既往STD（STD门诊患者，大学年龄男性和女性，女孩和男孩 在青少年医学诊所和健康儿童中看到）。 第二、 将在巴尔的摩市STD进行巢式病例对照研究 临床，以评估血清和局部抗体标志物， 降低衣原体感染风险的预测因子。 血清和生殖器 将前瞻性地收集所有诊所参与者的分泌物。 病例组（感染妇女）和对照组（未感染妇女的随机样本 或通过接触者追踪已知已被感染的未感染妇女， 暴露于衣原体）将被识别，并将 访问。 将比较病例和对照的抗体反应性 为了鉴定血清型特异性或种特异性抗体， 感染风险降低的预测因素。 更好地理解 单个衣原体抗原对人类免疫的贡献 对衣原体的反应和鉴定血清学标志物， 与保护免受衣原体感染有关， 疫苗研发工作。