INDUCTION OF PROTECTIVE IMMUNITY AGAINST CHLAMYDIA

诱导针对衣原体的保护性免疫力

• 批准号: 8446379
• 负责人: Francis O. Eko
• 金额: $ 32.57万
• 依托单位: MOREHOUSE SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-09-01 至 2015-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8446379
• 关键词: Achievement; Adjuvant; Affect; Antibiotic Therapy; Antibodies; Antigen-Presenting Cells; Antigens; B-Lymphocytes; Bacterial Sexually Transmitted Diseases; CD8B1 gene; Chlamydia; Chlamydia Infections; Chlamydia trachomatis; Coupled; Detection; Development; Economic Burden; Ectopic Pregnancy; Elements; FLT3 ligand; Frequencies; Genital system; Goals; HIV; HIV Infections; HIV-1; Healthcare Systems; Human; Immune; Immune response; Immune system; Immunity; Immunization; Immunoglobulin A; Immunoglobulin G; Immunologics; Individual; Infection; Infection Control; Infection prevention; Infertility; Lead; Ligands; Luciferases; Lymphogranuloma Venereum; Maintenance; Mediating; Membrane Proteins; Memory B-Lymphocyte; Molecular; Motivation; Mus; NF-kappa B; Pathology; Pathway interactions; Pelvic Inflammatory Disease; Play; Public Health; Recombinants; Relative (related person); Reporter; Risk; Role; Route; Severities; Sexually Transmitted Diseases; Signal Transduction; Symptoms; System; T cell response; T memory cell; T-Lymphocyte; T-Lymphocyte Subsets; Testing; Treatment Cost; Vaccination; Vaccine Design; Vaccines; Vibrio; Woman; base; cross reactivity; immune activation; immunoregulation; migration; p65; porin; prevent; prophylactic; protective efficacy; protein B; public health relevance; rectal; response; therapy development; transmission process; vaccine candidate; vaccine delivery; vaccine development; vaccine efficacy

DESCRIPTION (provided by applicant): Chlamydia trachomatis, composed of 15 odd serovars (A through K and L1 to L3) with serovars D through K and the lymphogranuloma venereum strains L1 - L3 causing sexually transmitted diseases (STDs), is the most common bacterial cause of STDs and if untreated often lead to severe complications, including pelvic inflammatory disease, ectopic pregnancy and infertility in women. Since most infected individuals do not seek treatment due to lack of obvious symptoms, prophylactic immunization will be the best option for preventing infection and controlling chlamydial diseases. An efficacious chlamydial vaccine should induce broad-based, long lasting immunity against the different chlamydial serovars. We previously showed that the recombinant Vibrio choerae ghost (rVCG) platform is an effective delivery system capable of simultaneously delivering multiple Chlamydia antigens to the immune system. The results suggested that achievement of a long-term, cross-protective chlamydial immunity is possible and would require the mucosal delivery of specific multiple chlamydial antigens and effective immunomodulation of host immune response. Thus, the goal of this proposal is to utilize an rVCG- based multisubunit vaccine candidate together with a molecular mucosal adjuvant to validate a mucosal route for vaccine delivery and enhancement of chlamydial immunity. We will examine how a combination of the mucosal route of administration and mucosal adjuvant affect the profile and quality of antibody and T cell response for protection against Chlamydia. We propose to test the overall hypothesis that intrarectal (IR) delivery of select multiple chlamydial antigens together with a molecular adjuvant will enhance genital tract immunity and provide broad-based, long-lasting protection against intravaginal challenge. In specific aim 1, we will establish that IR delivery of an rVCG-based vaccine together with Flt3 ligand (FL) will enhance long-term, cross- protective chlamydial immunity. Specific aim 2 will examine the effect of FL adjuvant on the profile and quality of immune effectors elicited by a chlamydial vaccine after rectal mucosal delivery. Finally, studies in Specific aim 3 will elucidate the molecular mechanisms involved in the induction of immune responses by an rVCG vaccine expressing FL and determine the migration pathway of antigen presenting cells after IR delivery of rVCG vaccine.

描述（由申请人提供）：沙眼衣原体，由15种奇数血清（a至k和l1至l3）组成，其血清de d d t in t t t k in k和k和lymphogrogrogrogrogromoloma l1 -l1 l1 -l3引起性传播性疾病（STD）（STD），是最常见的疾病的炎症，包括疾病的炎症，包括疾病的疾病，包括疾病的疾病，包括疾病的疾病，包括疾病的疾病，包括疾病的疾病，包括疾病的疾病，包括疾病的疾病，包括疾病，包括疾病的疾病疾病（包括疾病）。和女性不孕症。由于大多数受感染的人由于缺乏明显的症状而不寻求治疗，因此预防性免疫将是预防感染和控制衣原体疾病的最佳选择。有效的衣原体疫苗应诱发基于广泛的，持久的免疫力，以抵抗不同的衣原体血清射手。我们先前表明，重组弧菌Choerae Ghost（RVCG）平台是一个有效的输送系统，能够同时将多种衣原体抗原传递到免疫系统中。结果表明，实现长期，跨保护衣原体免疫是可能的，并且需要粘膜递送特定的多重衣原体抗原和有效的宿主免疫反应免疫调节。因此，该提案的目的是利用基于RVCG的多亚基疫苗候选者以及分子粘膜佐剂来验证粘膜途径，以供疫苗输送和增强衣原体免疫。我们将研究粘膜给药途径和粘膜佐剂的结合如何影响抗体和T细胞反应的概况和质量，以保护衣原体。我们建议测试总体假设，即直肠内（IR）选择多种衣原体抗原和分子佐剂将增强生殖道的免疫力，并提供广泛的基于基于持久的基于持久的抗阴道挑战的保护。在特定的目标1中，我们将确定基于RVCG的疫苗与FLT3配体（FL）一起递送将增强长期，跨保护性衣原体免疫。特定的目标2将检查FL辅助对直肠粘膜递送后衣原体疫苗引起的免疫效应子的特征和质量的影响。最后，在特定目标3中的研究将阐明通过表达FL的RVCG疫苗诱导免疫反应的分子机制，并确定IR递送RVCG疫苗后抗原呈现细胞的迁移途径。