Global Analysis of Treponema pallidum Antigens

描述（由申请人提供）：梅毒是一种慢性，多阶段感染引起的螺旋体梅毒螺旋体亚种。苍白球，仍然是美国和世界范围内的主要健康问题。不能培养T。体外苍白球的研究阻碍了对宿主-病原体相互作用相关因素的研究。对重要的T.梅毒抗原将是理解对感染的免疫反应的重要一步，并可能导致鉴定可用于梅毒免疫诊断或潜在地通过疫苗接种预防感染的蛋白质。 在以前的研究中，全球筛选908 T。蛋白质阵列中的pallidum基因产物鉴定了与梅毒患者和T.苍白球感染的兔子。这些研究的目的是确定这些抗原在抗T.梅毒感染和宿主-病原体相互作用。在特异性目标1中，新鉴定的高反应性T。梅毒抗原与一组来自人类梅毒患者的血清，因此它们在免疫应答中的重要性和在免疫诊断中的潜在用途将被确定。在具体目标2中，我们将评估这些新的T。通过测定兔模型中的免疫保护作用以及抗原的细胞定位和结合特性，研究了宿主-病原体相互作用中的苍白球抗原。 总之，梅毒是一种性传播疾病，尽管有有效的治疗方法，但在美国和其他国家都有重大的医疗，经济和社会影响。该项目的公共卫生效益将是鉴定抗原，可能改善梅毒的诊断，并可能导致开发有效的疫苗。

DESCRIPTION (provided by applicant): Syphilis is a chronic, multistage infection caused by the spirochete Treponema pallidum subsp. pallidum and still represents a major health problem in the United States and worldwide. Inability to culture T. pallidum in vitro has hampered the study of factors involved in host-pathogen interactions. A global analysis of important T. pallidum antigens would be an important step forward in understanding the immune response to infection, and may lead to the identification of proteins useful in immunodiagnosis of syphilis or, potentially, prevention of infection through vaccination. In previous studies, a global screening of 908 T. pallidum gene products in a protein array identified a subset of proteins that are highly reactive with serum from syphilis patients and T. pallidum-infected rabbits. The purpose of the proposed studies is to determine the importance of these antigens in the immune response against T. pallidum infection and in host-pathogen interactions. In Specific Aim 1, the reactivity of newly identified, highly reactive T. pallidum antigens with a panel of sera from human syphilis patients, and hence their importance in the immune response and potential use in immunodiagnosis, will be determined. In Specific Aim 2, we will assess the importance of these novel T. pallidum antigens in host-pathogen interactions by determining immunoprotection in the rabbit model and cellular location and binding properties of the antigens. In summary, syphilis is a sexually transmitted disease that, despite the availability of effective therapy, has a major medical, economic, and social impact both in the United States and other countries. The public health benefit of this project will be the identification of antigens that may improve the diagnosis of syphilis and may lead to the development of an effective vaccine against the disease.