Scanning Chlamydia proteome for vaccine antigens

扫描衣原体蛋白质组寻找疫苗抗原

• 批准号: 7394476
• 负责人: LUIS M DE LA MAZA
• 金额: $ 29.93万
• 依托单位: IMMPORT THERAPEUTICS, INC.
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-15 至 2009-09-16
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7394476
• 关键词: Abdominal Pain; Animals; Antibiotic Therapy; Antibiotics; Antibodies; Antigens; Area; Bacteria; Bioinformatics; Biology; Birth; Blindness; Body measure procedure; CD4 Positive T Lymphocytes; Caliber; Cell membrane; Cells; Child; Chlamydia; Chlamydia Infections; Chlamydia trachomatis; Chlamydophila pneumoniae; Chlamydophila psittaci; Chronic; Cicatrix; Clinical Trials; Cloning; Condition; Conjunctivitis; Country; Data; Development; Disease; Disease Outcome; Drug Formulations; Economics; Ectopic Pregnancy; Epithelial Cells; Eye Infections; Female; Genital system; Genomics; Goals; Gram-Negative Bacteria; Health; Hypersensitivity; Immune response; Immunization; Inbred BALB C Mice; Individual; Infection; Infertility; Laboratories; Lead; Length; Life; Localized; Lymphogranuloma Venereum; Measures; Mediating; Mouse Strains; Mus; Natural Immunity; Numbers; Open Reading Frames; Patients; Pelvic Inflammatory Disease; Phase; Phase II Clinical Trials; Play; Pneumonia; Populations at Risk; Prevalence; Preventive; Protein C; Protein Microchips; Proteins; Proteome; Proteomics; Protocols documentation; Reaction; Role; Route; Rupture; Sampling; Scanning; Screening procedure; Serological; Serum; Severities; Small Business Technology Transfer Research; Spottings; Subunit Vaccines; Systemic infection; Testing; Therapeutic; Time; Tissues; Trachoma; Vaccinated; Vaccine Antigen; Vaccines; Vagina; Week; Whole Organism; Woman; Work; base; genital infection; high throughput technology; mouse model; novel strategies; pathogen; plasmid DNA; prevent; respiratory; vaccine development; vaccine evaluation

DESCRIPTION (provided by applicant): Throughout the world Chlamydia trachomatis is the most common sexually transmitted bacterial pathogen. In areas with poor sanitary conditions C. trachomatis causes trachoma the most common cause of preventable blindness in the world. A majority of the genital C. trachomatis infections in women are asymptomatic. In addition, in symptomatic cases, unless therapy is implemented in a timely manner, long-term sequelae including, pelvic inflammatory disease, chronic abdominal pain, ectopic pregnancy and infertility, may develop. Children get infected at the time of birth and can develop conjunctivitis and pneumonia. Thus, the only practical approach to prevent these diseases is vaccinating the population at risk. Here we are going to utilize a high throughput approach to identify new potential candidate antigens for the formulation of a vaccine against C. trachomatis infections. The hypothesis we want to test is that antigens that can induce antibodies can protect against infection, and/or the long-term sequelae of a C. trachomatis infection, e.g., infertility. Using a new approach, developed by ImmPORT Therapeutics, Inc., we are going to clone and express all the proteins from C. trachomatis mouse pneumonitis (MoPn). The expressed proteins will be spotted onto a microarray chip. Three strains of mice will be vaccinated with live and UV-inactivated C. trachomatis MoPn using several mucosal and systemic routes of immunization. The animals will then be challenged intravaginally with C. trachomatis MoPn. To determine the severity and length of the genital infection vaginal cultures will be collected. Six weeks after the intravaginal challenge the mice will be euthanized and their genital tract examined for the presence of scar tissue and hydroxalpinx. Serum samples will be collected on a regular basis from the immunized and intravaginally challenged mice. These serum samples will be profiled based on the presence of antibodies to specific Chlamydia proteins using the microarray chip. Data will be analyzed to reveal any correlation between immune responses against specific subset of antigens and protection profile or disease state. Those proteins that are identified using the microarray chip, as potential vaccine antigens, will be subsequently tested in the phase II of the study for their ability to protect against a genital challenge. An efficacious vaccine against C. trachomatis will have a tremendous sanitary and economic impact throughout the world.

描述（由申请人提供）：沙眼衣原体是世界上最常见的性传播细菌病原体。在卫生条件差的地区，沙眼原体引起沙眼，这是世界上可预防失明的最常见原因。大多数女性生殖器沙眼衣原体感染是无症状的。此外，在有症状的病例中，除非及时实施治疗，否则可能出现盆腔炎、慢性腹痛、异位妊娠和不孕症等长期后遗症。儿童在出生时就被感染，并可能发展成结膜炎和肺炎。因此，预防这些疾病的唯一实际方法是为高危人群接种疫苗。在这里，我们将利用一种高通量的方法来鉴定新的潜在候选抗原，用于制定针对沙眼衣原体感染的疫苗。我们想要验证的假设是，可以诱导抗体的抗原可以防止感染和/或沙眼衣原体感染的长期后遗症，例如不孕症。利用一种由import Therapeutics， Inc.开发的新方法，我们将克隆和表达沙眼原体小鼠肺炎（MoPn）的所有蛋白。表达的蛋白质将被标记到微阵列芯片上。通过几种粘膜和全身免疫途径，对三株小鼠分别接种活的和紫外线灭活的沙眼衣原体MoPn。然后将对这些动物进行沙眼衣原体MoPn阴道内感染。为了确定生殖器感染的严重程度和持续时间，将采集阴道培养物。在阴道内注射六周后，这些老鼠将被安乐死，并检查它们的生殖道是否存在疤痕组织和羟化酶。将定期收集免疫小鼠和经阴道刺激小鼠的血清样本。这些血清样本将根据使用微阵列芯片对特定衣原体蛋白的抗体的存在进行分析。将对数据进行分析，以揭示针对特定抗原子集的免疫反应与保护概况或疾病状态之间的任何相关性。使用微阵列芯片识别的那些蛋白质，作为潜在的疫苗抗原，随后将在研究的第二阶段测试它们保护生殖器免受挑战的能力。一种有效的沙眼原体疫苗将对全世界的卫生和经济产生巨大影响。

项目成果

Identification of immunodominant antigens of Chlamydia trachomatis using proteome microarrays.

使用蛋白质组微阵列鉴定沙眼衣原体的免疫主导抗原。

• DOI: 10.1016/j.vaccine.2009.12.020
• 发表时间: 2010-04-09
• 期刊: VACCINE
• 影响因子: 5.5
• 作者: Molina, Douglas M.;Pal, Sukumar;Kayala, Mathew A.;Teng, Andy;Kim, Paul J.;Baldi, Pierre;Felgner, Philip L.;Liang, Xiaowu;de la Maza, Luis M.
• 通讯作者: de la Maza, Luis M.

Proteomic identification of immunodominant chlamydial antigens in a mouse model.

小鼠模型中免疫显性衣原体抗原的蛋白质组学鉴定。

• DOI: 10.1016/j.jprot.2012.08.017
• 发表时间: 2012
• 期刊: Journal of proteomics
• 影响因子: 3.3
• 作者: Teng,Andy;Cruz-Fisher,MariaI;Cheng,Chunmei;Pal,Sukumar;Sun,Guifeng;Ralli-Jain,Pooja;Molina,DouglasM;Felgner,PhilipL;Liang,Xiaowu;delaMaza,LuisM
• 通讯作者: delaMaza,LuisM