IMMUNOLOGY OF CHLAMYDIAL SURFACE ANTIGENS

该项目的目标是开发一种亚单位疫苗，用于 预防衣原体引起的性传播疾病 沙眼衣原体。为此，我们的目标是：(1)确定和 常见抗原性辅助性T细胞和中和性B细胞的鉴定 沙眼衣原体主要外膜蛋白表位：(Ii)连锁 在这些关键的T辅助细胞和B细胞保护表位中作为嵌合肽 免疫原，(Iii)嵌合体的免疫原性评价 多肽，以及(Iv)靶向嵌合肽以唤起持续的 粘膜免疫反应。 MOMP的抗原共同T辅助细胞和B细胞表位是 采用重组DNA和多肽图谱方法进行鉴定。一种合成纤维 与这些表位相对应的寡肽被共线性合成 并在小鼠和亚灵长类动物身上研究了其免疫原性。 嵌合T：B细胞肽在8个不同菌株中具有免疫原性 H-2同源基因B10小鼠。结合完整的小鼠抗肽抗体 衣原体，并能中和传染性 具有重要流行病学意义的沙眼衣原体体外血清型。亚人类 用该多肽免疫灵长类动物，它们的抗体反应是 类似的研究。A8-VDIV多肽免疫灵长类动物产生高产量 显示沙眼衣原体属常见物种的滴度IgG抗体 中和性能。 A8-VDIV多肽在不同品系小鼠体内的免疫原性 H-2不同，它在灵长类动物中的免疫原性，以及它的能力 针对多个沙眼衣原体血清型的靶向中和抗体 在嵌合肽的潜在用途方面是令人鼓舞的 免疫基因作为预防衣原体性病的实验性疫苗。未来 研究将集中在靶向嵌合肽以唤起粘膜 豁免权。这项工作将包括将多肽整合到 可生物降解微球及其不耐热菌的构建 毒素(LT)肽融合。

The goal of this project is the development of a subunit vaccine for the prevention of sexually transmitted diseases (STDs) caused by Chlamydial trachomatis. Towards this end our objectives are to: (i) identify and characterize antigenically common T-helper and neutralizing B-cell epitopes of the C. trachomatis major outer membrane protein, (ii) linkage of these key T-helper and B-cell protective epitopes as a chimeric peptide immunogen, (iii) evaluation of the immunogenic properties of the chimeric peptide, and (iv) targeting the chimeric peptide to evoke a sustained mucosal immune response. Antigenically common T-helper and B-cell epitopes of the MOMP were identified using recombinant DNA and peptide mapping methods. A synthetic oligopeptide corresponding to these epitopes was co-linearly synthesized and its immunogenic properties were studied in both mice and sub-primates. The chimeric T:B cell peptide was immunogenic in eight different strains of H-2 congenic B10 mice. Mouse anti-peptide antibodies bound to intact chlamydiae, and were capable of neutralizing the infectivity epidemiologically important C. trachomatis serovars in vitro. Sub-human primates were immunized with the peptide and their antibody responses were similarly studied. Primates immunized with peptide A8-VDIV produced high titer IgG antibodies that exhibited C. trachomatis species common neutralizing properties. The immunogenicity of peptide A8-VDIV in different strains of mice disparate at H-2, its immunogenicity in primates, and its ability to target neutralizing antibodies against multiple C. trachomatis serovars are encouraging in terms of the potential utility of the chimeric peptide immunogen as an experimental vaccine against chlamydial STDs. Future studies will focus on targeting the chimeric peptide to evoke mucosal immunity. This work will include incorporation of the peptide into biodegradable microspheres and the construction of E. coli heat labile toxin (LT) peptide fusions.