IMMUNOCHEMISTRY OF CHLAMYDIAL SURFACE ANTIGENS

对食蟹猴眼部衣原体感染进行了研究 评估表面抗原在(1)抵抗再感染和 (2)疾病的免疫致病机制。 (I)抵抗再感染。食蟹猴(猕猴) 感染了沙眼衣原体生物群，产生了急性 滤泡性结膜炎。泪液和血清的暂时性表现 检测与沙眼衣原体表面抗原反应的抗体 免疫印迹分析和放射免疫沉淀 自限性疾病。衣原体主要外膜蛋白(MOMOP) 被发现是猴子泪液IgA识别的主要免疫原 感染过程中的抗体。泪液IgA抗体MOMP反应为 对感染沙眼的血清型的特异性提示抗体 针对MOMP的抗原性独特的部分 防护性的。产生了针对MOMP的单克隆抗体，该抗体 识别的抗原独特表位，并被发现中和 该菌对小鼠的体内毒性和对猴的感染性 眼睛。纯化的天然MOMP和重组MOMP目前正在测试中 在猴子模型中作为亚单位疫苗。 (2)疾病的免疫致病机制。当给药到 免疫但不幼稚猴子的结膜，Triton X-100提取物 衣原体引起的炎症反应与 在患有原发性衣原体结膜炎的猴子身上观察到。这 炎症反应不是由于衣原体感染，而是 具有延迟型超敏反应的特点。抗原性 诱导这种有害免疫反应的部分不包含 保护性MOMP抗原。目前正在进行的研究旨在 这种抗原的特征。初步结果显示， 有害抗原是衣原体属常见的不耐热抗原。 这个项目的意义在于对 衣原体疾病的发病机制和一个亚单位的发育 衣原体疫苗。

Ocular chlamydial infections were studied in cynomolgus monkeys in order to evaluate the role of surface antigens in (1) resistance to reinfection and (ii) immunopathogenesis of disease. (i) Resistance to reinfection. Cynomolgus monkeys (Macaca fasicularis) were infected with a C. trachomatis trachoma biovar producing an acute follicular conjunctivitis. The temporal appearance of tear and serum antibodies reactive with C. trachomatic surface antigens were determined by immunoblotting analysis and radioimmunoprecipitation during this self-limiting disease. The chlamydial major outer membrane protein (MOMOP) was found to be the primary immunogen recognized by monkey tear IgA antibodies during infection. The tear IgA antibody MOMP response was specific for the infecting trachoma serovar suggesting that antibodies directed against antigenically unique portions of the MOMP were protective. Monoclonal antibodies were generated against the MOMP that recognized antigenically unique epitopes and were found to neutralize the in vivo toxicity of the organism for mice and infectivity for the monkey eye. Purified native MOMP and recombinant MOMP are currently being tested as a subunit vaccine in the monkey model. (ii) Immunopathogenesis of disease. When administered onto the conjunctivae of immune but not naive monkeys, a Triton X-100 extract of chlamydiae produced an inflammatory response indistinguishable from that observed in monkeys with primary chlamydial conjunctivitis. This inflammatory response was not due to chlamydial infection and was characteristic of a delayed-type hypersensitivity reaction. The antigenic fraction that induced this deleterious immune response did not contain the protective MOMP antigen. Studies are currently underway aimed at characterization of this antigen. Preliminary results show that the deleterious antigen is heat labile and common to the genus chlamydiae. The significance of this project lies in the understanding of the pathogenesis of chlamydial diseases and in the development of a subunit chlamydial vaccine.