Wang Ledan, Cai Yiqi, Xiong Yirong, Du Wangqi, Cen Danwei, Zhang Chanqiong, Song Yiling, Zhu Shanli, Xue Xiangyang, Zhang Lifang
Department of Gynecology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325035, Zhejiang, China.
Department of Gastrointestinal, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325035, Zhejiang, China.
Oncotarget. 2017 May 16;8(20):33241-33251. doi: 10.18632/oncotarget.16601.
Chlamydia trachomatis (Ct) is one of the most frequently encountered sexual infection all over the world, yielding tremendous reproductive problems (e.g. infertility and ectopic pregnancy) in the women. This work described the design of a plasmid vaccine that protect mice from Ct infection, and reduce productive tract damage by generating effective antibody and cytotoxic T cell immunity. The vaccine, s was composed of MOMP multi-epitope and HPV16L2 genes carried in pcDNA plasmid (i.e. pcDNA3.1/MOMP/HPV16L). In transfection, the vaccine expressed the chimeric genes (i.e. MOMP and HPV16L2), as demonstrated via western blot, RT-PCR and fluorescence imaging. In vitro, the vaccine transfected COS-7 cells and expressed the proteins corresponding to the genes carried in the vaccine. Through intramuscular immunization in BALB/c mice, the vaccine induced higher levels of anti-Ct IgG titer, anti-HPV16L2 IgG titer in serum and IgA titer in local mucosal secretions, compared to plasmid vaccines that carry only Ct MOMP multi-epitope or HPV16L2 chimeric component only. In mice intravaginally challenged with Ct, the vaccines pcDNA3.1/MOMP/HPV16L2 generated a higher level of genital protection compared to other vaccine formulations. Additionally, histochemical staining indicated that pcDNA3.1/MOMP/HPV16L2 eliminated mouse genital tract tissue pathologies induced by Ct infection. This work demonstrated that pcDNA/MOMP/HPV16L2 vaccine can protect against Ct infection by regulating antibody production, cytotoxic T cell killing functions and reducing pathological damage in mice genital tract. This work can potentially offer us a new vaccine platform against Ct infection.
沙眼衣原体(Ct)是全球最常见的性传播感染病原体之一,会给女性带来巨大的生殖问题(如不孕和宫外孕)。这项研究描述了一种质粒疫苗的设计,该疫苗可保护小鼠免受Ct感染,并通过产生有效的抗体和细胞毒性T细胞免疫来减少生殖道损伤。该疫苗由pcDNA质粒(即pcDNA3.1/MOMP/HPV16L)携带的MOMP多表位和HPV16L2基因组成。在转染过程中,如通过蛋白质免疫印迹法、逆转录-聚合酶链反应和荧光成像所证实的,该疫苗表达了嵌合基因(即MOMP和HPV16L2)。在体外,该疫苗转染了COS-7细胞并表达了与疫苗中携带基因相对应的蛋白质。通过对BALB/c小鼠进行肌肉注射免疫,与仅携带Ct MOMP多表位或仅携带HPV16L2嵌合成分的质粒疫苗相比,该疫苗诱导血清中产生了更高水平的抗Ct IgG滴度、抗HPV16L2 IgG滴度以及局部黏膜分泌物中的IgA滴度。在用Ct对小鼠进行阴道攻击后,与其他疫苗制剂相比,pcDNA3.1/MOMP/HPV16L2疫苗产生了更高水平的生殖系统保护作用。此外,组织化学染色表明,pcDNA3.1/MOMP/HPV16L2消除了由Ct感染引起的小鼠生殖道组织病变。这项研究表明,pcDNA/MOMP/HPV16L2疫苗可通过调节抗体产生、细胞毒性T细胞杀伤功能以及减少小鼠生殖道的病理损伤来预防Ct感染。这项研究有可能为我们提供一个针对Ct感染的新疫苗平台。