Characterization of a vaccine against Chlamydia trachomatis

描述（由申请人提供）：我们与葛兰素史克生物制品公司的合作者一起，根据人类体液和T细胞反应确定了几种新的衣原体疫苗候选抗原，随后进行了动物保护研究。优先考虑那些既能引起来自健康供体的PBMC的辅助性T型1 （Th1）反应，且衣原体血清阳性，又能保护啮齿动物生殖器衣原体感染模型的抗原。根据我们的初步数据，似乎对衣原体感染的免疫可能主要由T辅助1型免疫反应介导，需要诱导和募集特异性T细胞。我们建议进一步详细研究衣原体保护性免疫中涉及的免疫因素。基于血清和脾细胞的测定将用于确定抗体和t细胞对候选疫苗中蛋白质的特异性反应性水平。该项目将确定介导免疫的相关效应物，包括长期记忆，负责诱导这些效应物的抗原，并将评估我们开发的生殖器衣原体感染小鼠模型中的疫苗递送方法。本提案中概述的工作建立在我们之前在抗原表征、佐剂/配方和传染病疫苗递送方面的研究和专业知识的基础上。我们假设候选衣原体抗原，当适当地提交给免疫系统时，可能会集中免疫反应，提供长期的衣原体保护和预防疾病。这些优先重组抗原配以佐剂和人类可接受的递送系统，将在衣原体感染和疾病的小鼠模型中进行评估。沙眼衣原体细菌在全球范围内造成了许多痛苦。世界卫生组织估计，每年有280万美国人感染这种性传播形式的疾病，而眼部形式的疾病每年在非洲和亚洲造成600万例失明和1100万例倒睫。不幸的是，经过数十年的研究，可能由于衣原体的生物学复杂性，多种血清型的存在以及诱导保护性和病理性免疫反应的能力，疫苗尚未问世。

DESCRIPTION (provided by applicant): Together with our collaborators at GlaxoSmithKline Biologicals, we have identified several new Chlamydia vaccine candidate antigens based on human humoral and T cell responses followed by animal protection studies. Priority has been given to those antigens that both elicit a T helper type1 (Th1) response from PBMC from healthy donors that are seropositive for Chlamydia and protect in rodent models of genital chlamydial infection. Based on our preliminary data, it appears that immunity to Chlamydia infection may be mediated primarily by a T helper type 1 immune response, requiring the induction and recruitment of specific T cells. We propose to examine in further detail the immunological factors that are involved in protective immunity to Chlamydia. Both serum- and splenocyte - based assays will be utilized to determine the level of antibody- and T-cell specific reactivity against the proteins comprising the candidate vaccine. This project will define the relevant effectors mediating immunity, including long-term memory, the antigens responsible for inducing these effectors, and will evaluate methods of vaccine delivery in a mouse model of genital chlamydial infection which we have developed. The work outlined in this proposal builds on our previous studies and expertise in antigen characterization, adjuvants/ formulations and vaccine delivery for infectious diseases. We hypothesize that the candidate chlamydial antigens, when properly presented to the immune system, may focus the immune response, provide long-term protection against Chlamydia and prevent disease. These priority recombinant antigens formulated with adjuvants and delivery systems acceptable for human use will be evaluated in mouse models of Chlamydia infection and disease. Chlamydia trachomatis bacteria cause much misery around the globe. The World Health Organization estimates that 2.8 million Americans are infected with the sexually transmitted form of the disease each year, while the ocular form causes 6 million cases of blindness and 11 million cases of trichiasis annually in Africa and Asia. Unfortunately, after decades of research, a vaccine has not been available perhaps due to the biological complexity of Chlamydia, the existence of multiple serovars, and the capacity to induce both protective and pathological immune responses.