Chlamydia trachomatis proteomics

描述(申请人提供)：沙眼衣原体蛋白质组学：沙眼衣原体保护性和致病决定因素的全基因组图谱。沙眼衣原体泌尿生殖道感染在上生殖道引起炎症病理，可导致包括输卵管因素不孕在内的并发症。了解衣原体的致病机制和开发亚单位疫苗一直是现代衣原体研究的重点。然而，关于衣原体致病机制的知识仍然有限，也没有有效的疫苗。这可能主要是由于以前用于分析衣原体抗原的方法的局限性。尽管这些先前的方法已经提供了有用的信息，例如，揭示了抗MOMP抗体反应与保护性免疫的关系，以及抗HSP60抗体反应与发病机制的关系，但结果的范围有限。为了在了解衣原体致病机制和开发有效的亚单位疫苗方面取得重大进展，钟博士的实验室在过去5年中将所有沙眼衣原体开放阅读框架(ORF)表达为可溶性融合蛋白，并开发了高质量的全基因组规模蛋白质组阵列。该阵列允许检测线性和构象依赖的人类抗体。利用这个阵列，钟博士的实验室已经绘制了B细胞抗原组的图谱，并识别出沙眼衣原体的新的免疫优势抗原。在目前的资助中，钟博士将使用全基因组规模的蛋白质组阵列来描述感染沙眼衣原体的女性抗体和T细胞反应的抗原特异性，并识别与病理或保护性免疫相关的抗原。识别的抗原的生物学相关性将在细胞培养和动物模型系统中进行表征。将向研究界提供从拟议研究中获得的知识和积累的试剂。所获得的信息将为了解衣原体致病机制以及开发诊断试剂和亚单位疫苗奠定基础。 公共卫生相关性：通过在全基因组范围内识别和表征与病理和保护性免疫相关的沙眼衣原体抗原，这笔赠款将提供关于了解衣原体致病机制、开发诊断输卵管性因素不孕症的标记和构建有效亚单位疫苗的最先进知识。

DESCRIPTION (provided by applicant): C. trachomatis proteomics: Whole genome scale mapping of C. trachomatis protective & pathogenic determinants. Chlamydia trachomatis urogenital tract infection causes inflammatory pathologies in the upper genital tract, which can lead to complications including tubal factor infertility. Understanding the pathogenic mechanisms and developing subunit vaccines have been the major focuses in modern chlamydial research. However, knowledge on chlamydial pathogenesis remains limited and there is no effective vaccine. This may be mainly due to limitations in the approaches previously used for analyzing chlamydial antigens. Although these previous approaches have provided useful information, for example, revealing the association of anti-MOMP antibody responses with protective immunity and anti-HSP60 antibody responses with pathogenesis, the results are limited in scope. To make significant advancements in understanding chlamydial pathogenic mechanisms and developing effective subunit vaccines, Dr. Zhong's lab expressed all C. trachomatis open reading frames (ORFs) as soluble fusion proteins and developed a high quality whole genome scale proteome array in the past 5 years. This array has allowed the detection of both linear and conformation-dependent human antibodies. Using this array, Dr. Zhong's lab has mapped the B cell ANTIGENome and identified novel immunodominant antigens of C. trachomatis. In the current grant, Dr. Zhong will use the whole genome scale proteome array to profile the antigen specificities of both antibody and T cell responses in C. trachomatis infected-women and to identify antigens that are associated with pathology or protective immunity. The biological relevance of the identified antigens will be characterized in both cell culture and animal model systems. Both the knowledge gained and reagents accumulated from the proposed studies will be made available to the research community. The information obtained will lay the foundation for both understanding chlamydial pathogenic mechanisms and developing diagnostic reagents and subunit vaccines. PUBLIC HEALTH RELEVANCE: By identifying and characterizing C. trachomatis antigens that are associated with pathology and protective immunity on a whole genome scale, this grant will provide the most advanced knowledge on understanding chlamydial pathogenic mechanisms, developing markers for diagnosing tubal factor infertility and constructing effective subunit vaccines.