Six new Chlamydia epitopes

六个新的衣原体表位

• 批准号: 8426077
• 负责人: RAYMOND Morris JOHNSON
• 金额: $ 23.4万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-02-15 至 2015-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8426077
• 关键词: Address; Adolescent; Amino Acids; Antibiotic Therapy; Antibodies; Antigens; Applications Grants; Bacteria; Bacterial Sexually Transmitted Diseases; Binding; Biology; CD4 Positive T Lymphocytes; Cell Line; Cells; Chlamydia; Chlamydia Infections; Chlamydia trachomatis; Cicatrix; Consensus; Data; Dendritic Cells; Development; Disease; Ectopic Pregnancy; Epithelial; Epithelial Cells; Epithelium; Epitopes; Escherichia coli; Future; Genetic Recombination; Genital system; Genome; Genomics; Goals; Human; Immune response; Immunity; In Vitro; Incidence; Infection; Infertility; Investigation; Libraries; MHC Class II Genes; Maps; Mediating; Modeling; Mus; Mutagenesis; Pathway interactions; Peptides; Play; Prevalence; Process; Proteins; Public Health; Publishing; Recombinants; Relative (related person); Research; Research Personnel; Role; Source; Subunit Vaccines; T cell response; T-Cell Receptor; T-Lymphocyte; T-Lymphocyte Epitopes; Technology; Tubal Pregnancy; Vaccinated; Vaccine Antigen; Vaccines; Western Europe; Whole Organism; Woman; antigen processing; base; immunogenic; immunogenicity; immunopathology; in vivo; interest; major outer membrane protein; mouse model; mutant; novel; reproductive; research study; tool; trachoma vaccine; trait; vaccine candidate; vaccine development; young adult

DESCRIPTION (provided by applicant): Chlamydia trachomatis is the most common bacterial sexually transmitted disease in the developed world with a prevalence approaching 10% in adolescents and young adults. In women C. trachomatis infections ascend into the upper reproductive tract causing scarring that results in infertility and ectopic pregnancy. Antibiotic therapy has been ineffective in addressing the prevalence of the disease making development of a protective vaccine a logical approach to address this common infection. Existing data from the C. muridarum mouse model shows a correlation between a CD4 T cell clones ability to control replication of Chlamydia in epithelial cells in vitro and its ability to protect the reproductive tract in vivo. Similarly, existing vaccine data in the C. muridarum model has shown that not all Chlamydia antigens induce protective immunity. The major challenge for development of a protective Chlamydia vaccine is identifying which of the ~900 Chlamydia proteins is capable of inducing protective immunity. We hypothesize based on existing data that the protective epitopes will be found in the subset of Chlamydia proteins that are processed and presented by infected epithelial cells, generating a CD4 T cell response capable of controlling Chlamydia replication in epithelial cells. CD4 T cell clones that recognize and control C. muridarum replication in epithelial cells are logical tools for identifying candidate vaccine antigens. We propose using our unique epithelial cell lines, existing panel of Chlamdydia- specific CD4 T cell clones, and novel technologic expertise in generating Chlamydia mutants and recombinants to accomplish the following specific aims: #1 to identify six new "epithelial" CD4 epitope-source proteins using recombinant and mutant libraries of C. muridarum combined with genomic sequencing, #2 to investigate the role of epitope abundance on infected epithelial cells as a parameter for CD4 T cell-mediated control of C. muridarum replication in epithelial cells, #3 to investigate the ability of each identified epitope source protein to induce protective vaccine immunity in the C. muridarum mouse model.

描述（由申请人提供）：沙眼衣原体是发达国家最常见的细菌性传播疾病，在青少年和年轻人中的患病率接近10%。在女性中，C。沙眼感染上升到上生殖道，引起疤痕，导致不孕和异位妊娠。抗生素治疗在解决该疾病的流行方面一直无效，使得开发保护性疫苗成为解决这种常见感染的合乎逻辑的方法。现有的数据来自C.小鼠模型显示了CD4 T细胞克隆体外控制衣原体在上皮细胞中复制的能力与其体内保护生殖道的能力之间的相关性。同样，现有的疫苗数据在C。muridarum模型已经显示并非所有衣原体抗原都诱导保护性免疫。开发保护性衣原体疫苗的主要挑战是鉴定约900种衣原体蛋白中的哪一种能够诱导保护性免疫。我们假设基于现有的数据，保护性表位将被发现在衣原体蛋白的子集，被感染的上皮细胞加工和呈递，产生能够控制衣原体复制上皮细胞的CD4 T细胞反应。识别和控制C.上皮细胞中的鼠伤寒沙门氏菌复制是鉴定候选疫苗抗原的逻辑工具。我们建议使用我们独特的上皮细胞系、现有的衣原体特异性CD4 T细胞克隆组和产生衣原体突变体和重组体的新技术专长来实现以下特定目标：#1使用衣原体的重组和突变体文库鉴定六种新的“上皮”CD4表位源蛋白。结合基因组测序，#2研究表位丰度在感染上皮细胞上的作用，作为CD4 T细胞介导的C. #3，以研究每种鉴定的表位源蛋白诱导保护性免疫应答的能力。 C.小鼠模型。