Ningxia Key Laboratory of Clinical and Pathogenic Microbiology, General Hospital of Ningxia Medical University, Yinchuan, China.
Department of Medical Laboratory, School of Clinical Medicine, Ningxia Medical University, Yinchuan, China.
Helicobacter. 2017 Dec;22(6). doi: 10.1111/hel.12428. Epub 2017 Aug 29.
Therapeutic vaccination is a desirable alternative for controlling Helicobacter pylori (H. pylori) infection. Attachment to the gastric mucosa is the first step in establishing bacterial colonization, and adhesins, which are on the surface of H. pylori, play a pivotal role in binding to human gastric mucosa.
In the present study, we constructed a multivalent epitope-based vaccine named CFAdE with seven carefully selected antigenic fragments from four H. pylori adhesins (urease, Lpp20, HpaA and CagL). The specificity, immunogenicity and ability to produce neutralizing antibodies of CFAdE were evaluated in BALB/c mice. After that, its therapeutic efficacy and protective immune mechanisms were explored in H. pylori-infected Mongolian gerbils.
The results indicated that CFAdE could induce comparatively high levels of specific antibodies against urease, Lpp20, HpaA and CagL. Additionally, oral therapeutic immunization with CFAdE plus polysaccharide adjuvant (PA) significantly decreased H. pylori colonization compared with oral immunization with urease plus PA, and the protection was correlated with IgG and sIgA antibody and antigen-specific CD4 T cells.
This study indicated that the multivalent epitope-based vaccine, which targeted multiple adhesins in adherence of H. pylori to the gastric mucosa, is more effective than the univalent vaccine targeting urease only. This multivalent epitope-based vaccine may be a promising therapeutic candidate vaccine against H. pylori infection.
治疗性疫苗是控制幽门螺杆菌(H. pylori)感染的理想选择。黏附于胃黏膜是细菌定植的第一步,而黏附素是 H. pylori 表面的一种蛋白,在与人类胃黏膜结合中起关键作用。
本研究构建了一种名为 CFAdE 的多价表位疫苗,该疫苗包含来自 4 种 H. pylori 黏附素(尿素酶、Lpp20、HpaA 和 CagL)的 7 个精心挑选的抗原片段。在 BALB/c 小鼠中评估了 CFAdE 的特异性、免疫原性和产生中和抗体的能力。然后,在 H. pylori 感染的蒙古沙鼠中探索了其治疗功效和保护免疫机制。
结果表明,CFAdE 能诱导针对尿素酶、Lpp20、HpaA 和 CagL 的特异性抗体水平较高。此外,与单独用尿素酶加多糖佐剂(PA)口服免疫相比,CFAdE 加 PA 口服治疗性免疫能显著降低 H. pylori 定植,保护作用与 IgG 和 sIgA 抗体以及抗原特异性 CD4 T 细胞相关。
本研究表明,针对 H. pylori 黏附于胃黏膜的多个黏附素的多价表位疫苗比仅针对尿素酶的单价疫苗更有效。这种多价表位疫苗可能是一种有前途的针对 H. pylori 感染的治疗候选疫苗。