Recombinant C. trachomatis vaccine

重组沙眼衣原体疫苗

• 批准号: 7197954
• 负责人: LUIS M DE LA MAZA
• 金额: $ 37.36万
• 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/7197954
• 关键词: Abdominal Pain; Acute; Adjuvant; Animals; Area; Blindness; C57BL/6 Mouse; Chlamydia trachomatis; Chronic; Condition; Disease; Drug Formulations; Economics; Ectopic Pregnancy; Effectiveness; Embryo; Escherichia coli; Female; Fertility Rates; Genital system; Goals; Human; Immunization; Inbred BALB C Mice; Infection; Infertility; Length; Mucosal Immune Responses; Mus; Numbers; Patient currently pregnant; Pelvic Inflammatory Disease; Pneumonia; Populations at Risk; Preparation; Protocols documentation; Recombinants; Research Personnel; Route; Severities; Testing; Trachoma; Vaccinated; Vaccination; Vaccines; Vagina; Week; Woman; day; genital infection; major outer membrane protein; pathogen; prevent; programs

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，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。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。在这个提议中，我们想要验证一个假设，即用沙眼衣原体主要外膜蛋白（MOMP）配制的疫苗可以诱导雌性小鼠免受生殖器攻击的保护。为了实现这一目标，我们希望利用重组MOMP制备在大肠杆菌中表达的小鼠肺炎（MoPn）血清型。我们将首先优化BALB/c小鼠的疫苗接种方案，优化接种途径和佐剂配方，以诱导强烈的全身和粘膜免疫反应。在最后一次免疫后四周，小鼠将在生殖道内接受挑战。保护参数将包括：生殖道的组织病理学变化，阴道培养阳性小鼠的百分比，阴道脱落的严重程度和长度。然后将测试优化后的疫苗对C3H/HeN和C57BL/6小鼠的保护能力。随后将通过确定生育率和每只怀孕动物的胚胎数量来评估对长期后遗症的保护。该疫苗还将测试其诱导长期保护的功效。具体而言，在最后一次免疫接种后的60、120和180天，接种疫苗的动物将在生殖道受到挑战。最后，交叉保护将通过将重组MOMP制剂从MoPn和选定的人类血清型接种给小鼠，并确定其对其他人类血清型攻击的保护功效来建立。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，以防止沙眼衣原体对生殖器的攻击。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。