通过建立新西兰白兔免疫-感染模型评估梅毒螺旋体TP0136蛋白不同亚型抗原决定簇的交叉保护能力

黏附定植是梅毒感染宿主的关键一步，如何在感染早期阻断其黏附成为研究热点。研究表明：1）具有黏附作用的梅毒螺旋体TP0136蛋白存在多个亚型；2）不同亚型间存在部分交叉体液免疫反应；3）TP0136抗体可抑制梅毒螺旋体黏附，具有一定的免疫保护作用。通过建立新西兰白兔免疫-感染模型，筛选出TP0136不同亚型的B细胞和T细胞抗原决定簇，组成串联多价肽以评估其交叉保护能力，将有助于阻止梅毒感染进程。本项目拟通过：1）Fmoc固相合成法，合成梅毒螺旋体Nichol标准株、SS14流行株和GD1广东株的TP0136重叠肽；2）PEPSCAN技术和T淋巴细胞增殖试验，明确TP0136重叠肽的B细胞和T细胞表位；3）I-TASSER预测TP0136三维结构中抗原决定簇位置，构建多价串联肽；4）建立梅毒兔免疫-感染模型，评估多价肽交叉保护能力。本研究成果将为开发梅毒预防性疫苗或治疗性药物靶标奠定分子基础。

Adhesion and colonization are a key step of syphilis infection to the host. How to block syphilis adhesion in the early stage of infection has become a research hotspot. Studies have shown that: 1) there were multiple subtypes of Treponema pallidum subspecies pallidum TP0136 protein which with the ability of adhesion; 2)different subtypes had partial cross humoral immune response; 3) TP0136 antibody inhibited the adhesion of Treponema pallidum subspecies pallidum and had a certain immune protection effect. By establishing the syphilis infection and immune model in the New Zealand White rabbits, B-cell and T-cell epitopes of different subtypes of TP0136 were screened out, and multivalent tandem peptide were formed to evaluate their cross-protective ability, which would help prevent syphilis infection. This project intends to use: 1) Fmoc solid-phase synthesis method to synthesize TP0136 overlapping peptides of Treponema pallidum Nichol standard strain, SS14 epidemic strain and GD1 Guangdong strain; 2) PEPSCAN technology and T lymphocyte proliferation test to identify B cells and T cell epitopes of TP0136 overlapping peptide; 3) I-TASSER predicts the epitope positions in the three-dimensional structure of TP0136 and multivalent tandem peptide will be constructed; 4) Establishes the syphilis immune-infective rabbit models to evaluate the cross-protection of multivalent peptide. The results of this research will lay the molecular foundation for the development of syphilis preventive vaccines or therapeutic drug targets.