Characterization of a vaccine against Chlamydia trachomatis

描述（由申请人提供）：我们与GlaxoSmithKline Biologicals的合作者一起，根据人类体液和T细胞反应以及动物保护研究，确定了几种新的衣原体疫苗候选抗原。优先考虑那些抗原，这两个引发T辅助1型（Th 1）反应的PBMC从健康的捐助者是衣原体血清阳性和保护生殖器衣原体感染的啮齿动物模型。根据我们的初步数据，看来衣原体感染的免疫可能主要是由辅助性T细胞1型免疫应答介导的，需要特异性T细胞的诱导和募集。我们建议进一步详细研究参与衣原体保护性免疫的免疫因素。将利用基于血清和脾细胞的测定来确定针对包含候选疫苗的蛋白质的抗体和T细胞特异性反应性的水平。该项目将定义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以前在传染病抗原表征、佐剂/制剂和疫苗递送方面的研究和专业知识基础上。我们推测，当适当地呈递给免疫系统时，候选衣原体抗原可能会集中免疫应答，提供针对衣原体的长期保护并预防疾病。将在衣原体感染和疾病的小鼠模型中评价这些优先重组抗原与佐剂和人类可接受的递送系统一起配制。沙眼衣原体细菌在地球仪上造成了许多痛苦。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，而在非洲和亚洲，这种眼部形式每年造成600万例失明和1100万例倒睫。不幸的是，经过几十年的研究，疫苗还没有可用的可能是由于衣原体的生物学复杂性，存在多种血清型，并诱导保护性和病理性免疫反应的能力。

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.