Characterization of a vaccine against Chlamydia trachomatis

描述(由申请人提供)：与我们在葛兰素史克生物制药的合作者一起，我们根据人类体液和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。优先考虑的是那些既能从健康捐赠者的PBMC中引发Thelper Type1(Th1)反应的抗原，又能在衣原体感染的啮齿动物模型中保护衣原体。根据我们的初步数据，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，需要特定T细胞的诱导和募集。我们建议更详细地研究与衣原体保护性免疫有关的免疫学因素。基于血清和脾细胞的分析将被用来确定抗体和T细胞对构成候选疫苗的蛋白质的特异性反应水平。该项目将定义相关的调节免疫的效应器，包括长期记忆，负责诱导这些效应器的抗原，并将在我们开发的生殖器衣原体感染的小鼠模型中评估疫苗接种的方法。本提案中概述的工作建立在我们以前在抗原表征、佐剂/制剂和传染病疫苗交付方面的研究和专业知识的基础上。我们推测，候选衣原体抗原，当适当地呈现给免疫系统时，可能会集中免疫反应，提供对衣原体的长期保护，并预防疾病。这些用人类可接受的佐剂和递送系统配制的优先重组抗原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造成了许多苦难。世界卫生组织估计，每年有280万美国人感染这种通过性传播的疾病，而在非洲和亚洲，眼部疾病每年导致600万人失明，1100万人倒立。不幸的是，经过几十年的研究，可能由于衣原体生物学的复杂性、多个血清型的存在以及诱导保护性和病理性免疫反应的能力，尚未有疫苗可用。

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.