Department of Medicine, Division of Gastroenterology, Rhode Island Hospital & Warren Alpert Medical School of Brown University, Providence, RI 02903, USA. Steven
Vaccine. 2011 Mar 3;29(11):2085-91. doi: 10.1016/j.vaccine.2010.12.130. Epub 2011 Jan 12.
Helicobacter pylori is the leading cause of gastritis, peptic ulcer disease and gastric adenocarcinoma and lymphoma in humans. Due to the decreasing efficacy of anti-H. pylori antibiotic therapy in clinical practice, there is renewed interest in the development of anti-H. pylori vaccines. In this study an in silico-based approach was utilized to develop a multi-epitope DNA-prime/peptide-boost immunization strategy using informatics tools. The efficacy of this construct was then assessed as a therapeutic vaccine in a mouse model of gastric cancer induced by chronic H. pylori infection. The multi-epitope vaccine administered intranasally induced a broad immune response as determined by interferon-gamma production in ELISpot assays. This was associated with a significant reduction in H. pylori colonization compared with mice immunized with the same vaccine intramuscularly, given an empty plasmid, or given a whole H. pylori lysate intranasally as the immunogen. Total scores of gastric histological changes were not significantly different among the 4 experimental groups. These results suggest that further development of an epitope-based mucosal vaccine may be beneficial in eradicating H. pylori and reducing the burden of the associated gastric diseases in humans.
幽门螺杆菌是导致人类胃炎、消化性溃疡病和胃腺癌及淋巴瘤的主要原因。由于抗幽门螺杆菌抗生素治疗在临床上的效果逐渐降低,人们对开发抗幽门螺杆菌疫苗重新产生了兴趣。在这项研究中,我们利用基于计算机的方法,利用信息学工具开发了一种多表位 DNA 初免/肽增强免疫接种策略。然后,我们在慢性幽门螺杆菌感染诱导的胃癌小鼠模型中评估了这种构建物作为治疗性疫苗的效果。鼻内给予的多表位疫苗诱导了广泛的免疫反应,这可通过 ELISpot 测定干扰素-γ的产生来确定。与肌肉内给予相同疫苗、给予空质粒或给予鼻内作为免疫原的全幽门螺杆菌裂解物的小鼠相比,这种疫苗显著降低了幽门螺杆菌定植。4 个实验组的胃组织学变化总评分无显著差异。这些结果表明,进一步开发基于表位的黏膜疫苗可能有助于根除幽门螺杆菌,并减轻与人类相关的胃部疾病的负担。