ENHANCING MUCOSAL IMMUNITY TO TRICHOMONIASIS

增强粘膜对滴虫病的免疫力

基本信息

批准号：
2068600
负责人：
LYNETTE Bundy CORBEIL
金额：
$ 17.39万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
1993
资助国家：
美国
起止时间：
1993-08-01 至 1998-12-31
项目状态：
已结题

项目摘要

This proposal is designed to address the great need to enhance immune responses against microbial agents which cause sexually transmitted diseases (STDs). With diseases which are only (or primarily) transmitted sexually, enhanced immunity at the reproductive mucosa is key. We chose to study immunity at the female reproductive mucosa in trichomoniasis because a) trichomoniasis is a human STD of increasing importance, b) there is a bovine model of trichomoniasis in which immunity can be studied in the natural host and challenge infection can be done, c) we have experience with the bovine model, d) bovine trichomoniasis is one of the few STDs which can be controlled by vaccination. For these reasons, we will use the bovine trichomoniasis model to develop means to enhance mucosal immunity to a defined protective antigen. To accomplish this goal, our objectives are to: 1) immunize mice with purified trichomonad protective antigen TF1.17 mixed with alum, or Quil A adjuvants or conjugated to cholera toxin (CT) adjuvant. Intravaginal or subcutaneous routes will be used. IgG and IgA vaginal or serum antibodies to TF1.17 antigen will be quantitated by ELISA. 2) determine whether a better local immune response results after intravaginal administration of antigen/adjuvant with or without a foam delivery system in mice. 3) compare serum and vaginal antibody responses of cattle to TF1.17 antigen after vaginal immunization with adjuvants from above studies. 4) assess protection of cattle against trichomoniasis with TF1.17 antigen immunization using the best local and systemic vaccination formulations from the above studies. 5) investigate antigenic variation of weekly trichomonad isolates from the bovine challenge experiment (AIM 4). 6) compare vaginal and systemic isotypic antibody titers with protection in locally immunized, systemically immunized, and control cattle. 7) determine functions of IgA vs. IgG antibodies from vaginal secretions. 8) compare isotypic antibody responses in the uterus and vagina for each group of cattle with day of clearance of the organism and with stage of the estrus cycle. 9) determine relationships between enhanced immunogenicity and degree of inflammation in the vagina, cervix, uterus and oviducts of immunized and control cattle. These studies are expected to show which adjuvant (or antigen-adjuvant conjugates), routes and delivery systems enhance genital mucosal immunity resulting in enhanced protection against an important STD. The results should have broad significance since vaccines are unavailable to protect against human diseases which are primarily transmitted sexually.

该提案旨在解决增强免疫力的巨大需求针对引起性传播疾病的微生物的反应疾病（性病）。对于仅（或主要）传播的疾病在性方面，增强生殖粘膜的免疫力是关键。我们选择了研究女性生殖粘膜对滴虫病的免疫力因为 a) 滴虫病是一种日益重要的人类性传播疾病，b) 有一种滴虫病牛模型，可以通过该模型获得免疫力在自然宿主中进行研究并攻击感染可以完成，c）我们有牛模型经验，d) 牛滴虫病是其中之一少数可以通过疫苗接种来控制的性传播疾病。对于这些由于原因，我们将使用牛滴虫病模型来开发方法增强对特定保护性抗原的粘膜免疫。为了完成这个目标，我们的目标是： 1)用纯化的滴虫保护性抗原TF1.17免疫小鼠与明矾或 Quil A 佐剂混合或与霍乱毒素 (CT) 缀合佐剂。将使用阴道内或皮下途径。 IgG 和 IgA TF1.17 抗原的阴道或血清抗体将通过以下方法进行定量酶联免疫吸附试验。 2) 确定是否会产生更好的局部免疫反应阴道内给予抗原/佐剂，有或没有泡沫小鼠体内的递送系统。 3) 比较牛对TF1.17的血清和阴道抗体反应使用上述研究的佐剂进行阴道免疫后的抗原。 4) 用TF1.17抗原评估牛对滴虫病的保护作用使用最佳的局部和全身疫苗接种配方进行免疫接种从上述研究来看。 5) 研究每周滴虫分离物的抗原变异牛挑战实验（AIM 4）。 6) 比较阴道和全身同型抗体滴度与保护作用在局部免疫、系统免疫和对照牛中。 7) 确定阴道分泌物中 IgA 与 IgG 抗体的功能。 8) 比较子宫和阴道中每种抗体的同型抗体反应一组牛，其微生物清除日和阶段为发情周期。 9) 确定增强的免疫原性和程度之间的关系免疫接种者的阴道、子宫颈、子宫和输卵管炎症控制牛。这些研究有望表明哪种佐剂（或抗原佐剂）缀合物）、途径和递送系统增强生殖器粘膜免疫从而增强对重要性传播疾病的保护。结果由于疫苗无法提供保护，因此应该具有广泛的意义预防主要通过性传播的人类疾病。