IMMUNOCHEMISTRY OF CHLAMYDIAL SURFACE ANTIGENS

该项目的直接目标是定义和分子 描述衣原体表面成分的毒性 在宿主免疫应答中重要的决定簇或抗原 衣原体感染 长期目标是： 了解衣原体如何与真核细胞相互作用并感染真核细胞 细胞，（ii）确定衣原体疾病的发病机制， (iii)鉴定用于开发重组体靶抗原 预防和/或控制人类衣原体疾病的疫苗。 我们先前已经表明，对衣原体的免疫反应 感染具有保护性和有害成分。 的 与这些应答相关的抗原是不同的。 的 保护性抗原是主要的外膜蛋白（MOMP）， 有害抗原是57-kDa蛋白质。 MOMP基因来自 几个C。沙眼血清型已被克隆和测序。 血清型、血清群和种特异性表位已经被 用一组保护性单克隆抗体定位在MOMP上 （MAbs）。 序列分析表明，MOMP基因编码的蛋白质 具有高度保守的区域，对称地被四个 短可变结构域（VD）。 VD具有连续的抗原性， 保护性单克隆抗体识别的决定因素。 表面蛋白水解 完整的衣原体与胰蛋白酶选择性地切割这些 VDs，并消除衣原体对HeLa细胞的附着。 这些 研究结果表明MOMP是衣原体粘附，并提示， 这些VD中的连续序列是潜在的疫苗 候选抗原 目前的研究是针对识别 MOMP T细胞决定簇和活肠 表达共线保护性MOMP B细胞的疫苗载体 决定簇与肠疫苗活载体的构建 表达共线性保护性MOMP B细胞决定簇和T细胞决定簇， 辅助细胞决定簇作为抗原性杂合蛋白。 保护 MOMP序列正在被克隆并表达为抗原杂合体 LamB蛋白在S.鼠伤寒沙门氏菌和Sabin 1型的VP 1 疫苗株。 这些疫苗的免疫原性和疫苗效力 目前正在评估感染性重组载体。

The immediate goals of this project are to define and molecularly characterize chlamydial surface components that are virulence determinants or antigens of importance in the hosts immune response to chlamydial infection. The long-term objectives are to: (i) understand how chlamydiae interact with and infect eukaryotic cells, (ii) define pathogenetic mechanisms of chlamydial disease, (iii) identify target antigens for development of a recombinant vaccine to prevent and/or control chlamydial diseases in humans. We have previously shown that the immune response to chlamydial infection has both protective and deleterious components. The antigens associated with these responses are distinct. The protective antigen is the major outer membrane protein (MOMP) and the deleterious antigen is a 57-kDa protein. The MOMP genes from several C. trachomatis serovars have been cloned and sequenced. Serotype, serogroup, and species-specific epitopes have been located on MOMP with a panel of protective monoclonal antibodies (MAbs). Sequence analysis showed the MOMP genes encode proteins with highly conserved regions interrupted symmetrically by four short variable domains (VD). The VDs possess contiguous antigenic determinants recognized by protective MAbs. Surface proteolysis of intact chlamydiae with trypsin selectively cleaves within these VDs and abolishes attachment of chlamydiae to HeLa cells. These findings implicate MOMP as a chlamydial adhesion and suggest that the contiguous sequences within these VDs are potential vaccine candidate antigens. Current studies are directed at identification of MOMP T-cell determinants and the construction of live enteric vaccine vectors expressing co-line protective MOMP B-cell determinants and the construction of live enteric vaccine vectors expressing co-linear protective MOMP B-cell determinants and T- helper cell determinants as antigenic hybrid proteins. Protective MOMP sequences are being cloned and expressed as antigenic hybrids of the LamB protein in S. typhimurium and VP1 of the Sabin type 1 vaccine strain. The immunogenicity and vaccine efficacy of these infectious recombinant vectors is currently being evaluated.