Novel Chlamydia Vaccine Candidates

尽管迫切需要并广泛努力制定预防沙眼衣原体泌尿生殖道感染的战略，但目前还没有有效的疫苗可用。这可能主要是由于对衣原体基因组编码的所有蛋白的抗原性和免疫原性缺乏了解。以前的疫苗研究往往集中在少数几个选定的抗原上，如主要外膜蛋白(MOMP)，这些分析中的许多都是基于变性蛋白或多肽。现有的衣原体基因组序列使得在构象依赖分析中对所有衣原体蛋白的抗原性和免疫原性进行全面分析成为可能。沙眼衣原体基因组编码大约300个假设的ORF，其中许多在衣原体中高度保守，也是唯一的。为了寻找新的候选疫苗，我们克隆了大约400个ORF，约占衣原体基因组的50%，包括编码所有假想蛋白和其他可能作为疫苗候选或已被广泛研究为疫苗候选或致病决定因素的ORF。我们建议使用400个衣原体可溶蛋白的微孔板来系统地分析STD患者对衣原体感染的抗体和T细胞反应，这将使我们能够识别新的免疫优势抗原。这些新的抗原将在动物模型中进一步评估它们诱导针对衣原体泌尿生殖道感染的保护性免疫的能力。我们的目标是获得足够的信息，用于开发有效的人体衣原体疫苗。

Despite the urgent need for and the extensive efforts in developing strategies to prevent C. trachomatis urogenital tract infection, no effective vaccine is available. This may be mainly due to lack of knowledge on antigenicity and immunogenicity of all proteins encoded by chlamydial genome. Previous vaccine studies were often focused on a few selected antigens such as the major outer membrane protein (MOMP) and many of these analyses were based on denatured proteins or peptides. The available chlamydial genome sequences have made it possible to obtain a comprehensive analysis of antigenicity and immunogenicity of all chlamydial proteins in conformation-dependent assays. The C. trachomatis genome encodes approximately 300 hypothetical ORFs, many of which are both highly conserved among and unique to chlamydiae. To search for novel vaccine candidates, we have cloned approximately 400 ORFs that represent approximately 50% of the chlamydial genome, including ORFs coding for all hypothetical proteins and others that may possess the potential as vaccine candidates or have been extensively studied as vaccine candidates or pathogenic determinants. We are proposing to use microplates arrayed with each of the 400 chlamydial soluble proteins to systematically analyze both antibody and T cell responses to chlamydial infection in STD patients, which should allow us to identify novel immunodominant antigens. These novel antigens will be further evaluated for their ability to induce protective immunity against chlamydial urogenital infection in animal models. Our goal is to acquire sufficient information for developing effective chlamydial vaccines in humans.