沙眼衣原体(Ct)持续感染时既逃避免疫又具耐药性，故易复发致异位妊娠、不孕等后果。基于单抗的靶向治疗是目前肿瘤和感染性疾病治疗中具前景的新手段，但其组织渗透性弱及副作用大等问题需解决。亲和体(affibody)分子能以高亲和力与靶蛋白特异结合，且穿透性强、稳定性好和易制备等诸多优点，在靶向治疗方面比单抗更具优势。颗粒酶B可作为单抗负载毒素通过诱导靶细胞凋亡而被用于肿瘤靶向治疗。本研究拟通过基因工程和噬菌体展示技术，筛选Ct主要外膜蛋白(MOMP)特异affibody分子，并以其为载体携带颗粒酶B，通过原核表达系统制备重组毒素蛋白，在体外细胞水平检测MOMP特异性重组毒素蛋白对Ct的靶向结合和对持续性Ct感染的清除作用，结合小鼠Ct生殖道感染模型，评价MOMP特异性重组毒素蛋白对Ct靶向治疗的有效性和安全性。本研究为发展基于MOMP亲和体的Ct持续感染特异性靶向治疗提供新途径。

The characteristics of persistent Chlamydia trachomatis (Ct) infection are immune evasion and antibiotic resistance, therefore, persistent infection and the high risk of recurrence result in ectopic pregnancy and tubal infertility. Targeted therapy based on monoclonal antibodies (mAb) is the most promising way for tumor and infectious diseases. However, applications of mAb in medicine are limited because of its weakness tissue penetration and adverse side effects. Affibody molecules bind specifically to target protein with high affinity. In addition, affibody molecules have more advantages over mAb, such as higher tissue penetration, more robust stability against heat and enzymes, and relative low production costs. Granzyme B is a serine protease produced by cytotoxic lymphotytes and capable of inducing rapid target cell death by apoptosis, so, GrB is widely used in tumor targeted therapy bases on mAb. In the present study, we intend to screen and identify Ct MOMP specific affibody by genetic engineering and phage display technology. Then, granzyme B (GrB) will be used as the toxin, MOMP specific affibody-GrB recombinant protein will be prepared. The specific binding of affibody-GrB to Ct and clearance of Ct will be investigated further in cell culture model of persistent Ct infection. Combined with animal experiment of Ct tract infection mouse model in vivo, the efficacy and safety of MOMP specific affibody-GrB in target therapy for Ct will be evaluated. This study will provide a new way for the target therapy based on affibody for infectious diseases.