Evaluation of CPAF Mediated Anti-Chlamydial Immunity in the Guinea Pig

描述(申请人提供)：沙眼衣原体是全球细菌性传播疾病的主要原因。未经治疗的生殖器衣原体感染会导致严重的后遗症，如盆腔炎、宫外孕和不孕症。目前还没有获得许可的疫苗，这种疫苗被认为是限制衣原体引起的发病率的理想方法。衣原体蛋白酶样活性因子(CPAF)是一种高度保守的细菌蛋白，分泌到宿主细胞质中。我们的实验室已经证明了重组(R)CPAF(血清型L2)鼻腔接种对小鼠生殖器衣原体感染和病理的保护作用。这种保护是由抗原特异性的CD4+T细胞介导的，并高度依赖于内源性干扰素-3的诱导。鉴于(1)rCPAF疫苗在小鼠模型中对生殖器衣原体感染产生保护性免疫的广泛免疫学特征，以及(2)豚鼠对衣原体感染的致病机制和免疫力已被证明与人类的衣原体生殖器感染非常相似，我们假设“rCPAF疫苗将诱导对豚鼠生殖器衣原体感染引起的炎症病理的保护性免疫”。我们建议翻译和验证rCPAF在另一种动物模型上的保护效果，该动物模型是豚鼠内涵性结膜炎(GPIC)的病原体。这些发现的结果将为人类使用的有效抗衣原体疫苗的设计提供重要的见解。这项研究将使罗杰·兰克博士(支持信)建立的豚鼠生殖器衣原体感染模型得以推广，该模型已在转译疫苗研究中有限使用。此外，豚鼠基因组测序的完成将导致用于鉴定的免疫试剂的开发，这将进一步促进该动物模型在科学界的使用。

DESCRIPTION (provided by applicant): Chlamydia trachomatis is the leading cause of bacterial sexually transmitted disease worldwide. Untreated genital chlamydial infections cause serious sequelae such as pelvic inflammatory disease, ectopic pregnancy, and infertility. A licensed vaccine, which is considered to be the ideal way to limit Chlamydia-induced morbidity, is currently not available. Chlamydial protease- like activity factor (CPAF) is a highly conserved bacterial protein secreted into the host cytosol. Our laboratory has shown the protective efficacy of intranasal vaccination with recombinant(r) CPAF (serovar L2) against genital chlamydial infection and pathology in mice. This protection is mediated by antigen-specific CD4+ T cells and highly dependent on the induction of endogenous IFN-3. Given (1) our extensive immunological characterization of rCPAF vaccination in conferring protective immunity against genital chlamydial infection in the mouse model, and (2) that the pathogenesis and immunity to chlamydial infection in guinea pigs has been shown to be remarkably similar to chlamydial genital infection in humans, we hypothesize that "vaccination with rCPAF will induce protective immunity against inflammatory pathology induced by genital chlamydial infection in guinea pigs". We propose to translate and validate the protective efficacy of rCPAF in an alternative animal model the guinea pig with C. caviae, the causative agent of guinea pig inclusion conjunctivitis (GPIC). The results obtained from these findings will provide important insights into the design of an effective anti-chlamydial vaccine for human use. This study will enable propogation of the guinea pig model of genital chlamydial infection established by Dr. Roger Rank (letter of support), which has been put to limited use in translational vaccine studies. Moreover, the completion of the sequencing of the guinea pig genome will result in the development of immunological reagents for characterization, which will further facilitate the use of this animal model in the scientific community.