Recombinant C. trachomatis vaccine

重组沙眼衣原体疫苗

• 批准号: 7763165
• 负责人: LUIS M DE LA MAZA
• 金额: $ 37.03万
• 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/7763165
• 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）：全世界沙眼衣原体是最常见的性传播细菌病原体。在卫生条件较差的地区，沙眼炎会导致沙丘瘤，这是世界上可预防失明的最常见原因。女性的大多数生殖器梭状芽胞庭感染无症状。此外，在有症状的情况下，除非及时实施治疗，否则可能会发展出长期后遗症，包括骨盆炎性疾病，慢性腹痛，异位妊娠和不育。因此，预防这些疾病的唯一实际方法是为处于危险中的人群接种疫苗。在此提案中，我们要检验以下假设：用沙眼甲状腺梭形集型的主要外膜蛋白（MOMP）配制的疫苗可以诱导雌性小鼠的保护，以防止生殖器挑战。为了实现这一目标，我们希望利用在大肠杆菌中表达的小鼠肺炎（MOPN）血清的重组MOMP制备。我们将首先优化BALB/C小鼠中的疫苗接种方案，用于途径和辅助配方，以诱导强烈的系统性和粘膜免疫反应。最后一次免疫后四周的生殖道中，小鼠将受到挑战。保护参数将包括：生殖道的组织病理学变化，阴道阳性培养的小鼠的百分比以及阴道脱落的长度。然后，将对优化的疫苗保护其保护C3H/HEN和C57BL/6小鼠的能力。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，在最后一次免疫后，在60、120和180天的生殖道中，接种疫苗的动物将受到挑战。最后，通过用MOPN和选择人类血清的重组MOMP制剂为小鼠接种小鼠，并确定它们的功效以防止对其他人类血清的挑战，从而确定了交叉保护。总而言之，我们的目标是利用重组MOMP制备来建立疫苗接种方案，以防止对沙眼梭状芽孢杆菌的生殖器挑战。针对沙aratomis的有效疫苗将在全世界产生巨大的卫生和经济影响。