壳聚糖作为幽门螺杆菌治疗性疫苗的佐剂。
Chitosan as an adjuvant for a Helicobacter pylori therapeutic vaccine.
作者信息
Gong Yanfeng, Tao Liming, Wang Fucai, Liu Wei, Jing Lei, Liu Dongsheng, Hu Sijun, Xie Yong, Zhou Nanjin
机构信息
Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330000, P.R. China.
Department of Obstetrics, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330000, P.R. China.
出版信息
Mol Med Rep. 2015 Sep;12(3):4123-4132. doi: 10.3892/mmr.2015.3950. Epub 2015 Jun 17.
The aim of the present study was to delineate the therapeutic effect of a Helicobacter pylori vaccine with chitosan as an adjuvant, as well as to identify the potential mechanism against H. pylori infection when compared with an H. pylori vaccine, with cholera toxin (CT) as an adjuvant. Mice were first infected with H. pylori and, following the establishment of an effective infection model, were vaccinated using an H. pylori protein vaccine with chitosan as an adjuvant. Levels of H. pylori colonization, H. pylori‑specific antibodies and cytokines were determined by enzyme‑linked immunosorbent assay. The TLR4 and Foxp3 mRNA and protein levels were determined by reverse transcription polymerase chain reaction and immunohistochemistry, respectively. It was identified that the H. pylori elimination rate of the therapeutic vaccine with chitosan as an adjuvant (58.33%) was greater than the therapeutic vaccine with CT as an adjuvant (45.45%). The therapeutic H. pylori vaccine with chitosan as an adjuvant induced significantly greater antibody and cytokine levels when compared with the control groups. Notably, the IL‑10 and IL‑4 levels in the groups with chitosan as an adjuvant to the H. pylori vaccine were significantly greater than those in the groups with CT as an adjuvant. The mRNA expression levels of TLR4 and Foxp3 were significantly elevated in the mice that were vaccinated with chitosan as an adjuvant to the H. pylori vaccine, particularly in mice where the H. pylori infection had been eradicated. The H. pylori vaccine with chitosan as an adjuvant effectively increased the H. pylori elimination rate, the humoral immune response and the Th1/Th2 cell immune reaction; in addition, the therapeutic H. pylori vaccine regulated the Th1 and Th2 response. The significantly increased TLR4 expression and decreased CD4+CD25+Foxp3+Treg cell number contributed to the immune clearance of the H. pylori infection. Thus, the present findings demonstrate that in mice the H. pylori vaccine with chitosan as an adjuvant exerts an equivalent immunotherapeutic effect on H. pylori infection when compared with the H. pylori vaccine with CT as an adjuvant.
本研究的目的是阐明以壳聚糖为佐剂的幽门螺杆菌疫苗的治疗效果，并确定与以霍乱毒素（CT）为佐剂的幽门螺杆菌疫苗相比，其对抗幽门螺杆菌感染的潜在机制。首先用幽门螺杆菌感染小鼠，在建立有效的感染模型后，使用以壳聚糖为佐剂的幽门螺杆菌蛋白疫苗进行接种。通过酶联免疫吸附测定法测定幽门螺杆菌定植水平、幽门螺杆菌特异性抗体和细胞因子水平。分别通过逆转录聚合酶链反应和免疫组织化学法测定TLR4和Foxp3的mRNA和蛋白水平。结果发现，以壳聚糖为佐剂的治疗性疫苗的幽门螺杆菌清除率（58.33%）高于以CT为佐剂的治疗性疫苗（45.45%）。与对照组相比，以壳聚糖为佐剂的治疗性幽门螺杆菌疫苗诱导的抗体和细胞因子水平显著更高。值得注意的是，以壳聚糖为佐剂的幽门螺杆菌疫苗组中的IL-10和IL-4水平显著高于以CT为佐剂的组。在以壳聚糖为佐剂接种幽门螺杆菌疫苗的小鼠中，TLR4和Foxp3的mRNA表达水平显著升高，尤其是在幽门螺杆菌感染已被根除的小鼠中。以壳聚糖为佐剂的幽门螺杆菌疫苗有效提高了幽门螺杆菌清除率、体液免疫反应和Th1/Th2细胞免疫反应；此外，治疗性幽门螺杆菌疫苗调节了Th1和Th2反应。TLR4表达的显著增加和CD4+CD25+Foxp3+调节性T细胞数量的减少有助于幽门螺杆菌感染的免疫清除。因此，本研究结果表明，在小鼠中，与以CT为佐剂的幽门螺杆菌疫苗相比，以壳聚糖为佐剂的幽门螺杆菌疫苗对幽门螺杆菌感染具有同等的免疫治疗效果。
Zotero 插件