Recombinant C. trachomatis vaccine

重组沙眼衣原体疫苗

• 批准号: 7559527
• 负责人: LUIS M DE LA MAZA
• 金额: $ 37.4万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-03-16 至 2012-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7559527
• 关键词: Acute; Adjuvant; Affect; Age-Months; Animal Model; Animals; Antibiotics; Area; Arthritis; Blindness; C57BL/6 Mouse; Cervicitis; Chlamydia; Chlamydia Infections; Chlamydia muridarum; Chlamydia trachomatis; Clinical; Conjunctivitis; Country; Disease; Drug Formulations; Ectopic Pregnancy; Effectiveness; Embryo; Endocarditis; Epididymitis; Escherichia coli; Eye; Female; Fertility Rates; Genital system; Goals; Human; Immunization; Inbred BALB C Mice; Individual; Infection; Infertility; Lead; Length; Lymphogranuloma Venereum; Meningoencephalitis; Modeling; Mucosal Immune Responses; Mus; Myocarditis; Newborn Infant; Organism; Ovarian; Partner in relationship; Pelvic Inflammatory Disease; Pneumonia; Populations at Risk; Preparation; Proctitis; Protocols documentation; Recombinant Vaccines; Recombinants; Reporting; Research Personnel; Resources; Route; Severities; Synthetic Antigens; Testing; Time; Trachoma; Urethritis; Vaccinated; Vaccination; Vaccines; Vagina; Woman; base; chronic abdominal pain; economic impact; genital infection; major outer membrane protein; male; mouse model; pathogen; pregnant; prevent; programs; prostatitis; research study; response; sexually active

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. Thus, the only practical approach to prevent these diseases is vaccinating the population at risk. In this proposal we want to test the hypothesis that a vaccine formulated with the C. trachomatis major outer membrane protein (MOMP) can induce protection in female mice against a genital challenge. To achieve this goal we want to utilize a recombinant MOMP preparation of the mouse pneumonitis (MoPn) serovar expressed in Escherichia coli. We will first optimize the vaccination protocol in BALB/c mice for the route and adjuvant formulation so as to induce strong systemic and mucosal immune responses. Mice will be challenged in the genital tract at four weeks after the last immunization. Parameters of protection will include: histopathological changes in the genital tract, percentage of mice with positive vaginal cultures and severity and length of vaginal shedding. The optimized vaccine will then be tested for its ability to protect C3H/HeN and C57BL/6 mice. Protection against long-term sequelae will subsequently be evaluated by determining fertility rates and the number of embryos per pregnant animal. The vaccine will also be tested for its efficacy for inducing long-term protection. Specifically, vaccinated animals will be challenged in the genital tract at 60, 120 and 180 days after the last immunization. Finally, cross-protection will be established by vaccinating mice with recombinant MOMP preparations from MoPn and selected human serovars and determining their efficacy to protect against a challenge with the other human serovars. In conclusion, our goal is to establish a vaccination protocol utilizing a recombinant MOMP preparation to protect against a genital challenge with C. trachomatis. 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C.沙眼是世界上最常见的可预防失明的原因。生殖器C.妇女的沙眼感染是无症状的。此外，在有症状的病例中，除非及时进行治疗，否则可能会出现长期后遗症，包括盆腔炎、慢性腹痛、异位妊娠和不孕症。因此，预防这些疾病的唯一切实可行的办法是为高危人群接种疫苗。在这个提议中，我们想验证一个假设，即用C.沙眼衣原体主要外膜蛋白（MOMP）可以诱导保护雌性小鼠免受生殖器攻击。为了实现这一目标，我们希望利用重组MOMP制备的小鼠肺炎（MoPn）血清型大肠杆菌中表达。我们将首先在BALB/c小鼠中优化疫苗接种方案的途径和佐剂配方，以诱导强烈的全身和粘膜免疫应答。在最后一次免疫接种后4周，在生殖道中激发小鼠。保护参数将包括：生殖道的组织病理学变化、阴道培养物阳性的小鼠百分比以及阴道脱落的严重程度和长度。然后将测试优化的疫苗保护C3 H/HeN和C57 BL/6小鼠的能力。随后将通过测定生育率和每只妊娠动物的胚胎数量来评价对长期后遗症的保护。该疫苗还将测试其诱导长期保护的效力。具体而言，将在末次免疫后60、120和180天对接种动物的生殖道进行攻毒。最后，通过用来自MoPn和选定的人血清型的重组MOMP制剂接种小鼠，并确定其针对其他人血清型攻击的保护效力，建立交叉保护。总之，我们的目标是建立一种利用重组MOMP制剂的疫苗接种方案，以保护免受C.沙眼一种有效的抗C.沙眼将对全世界的卫生和经济产生巨大影响。