重组幽门螺杆菌疫苗免疫保护作用与免疫后胃炎

Study on the protective immune mechanism of recombinant Helicobacter pylori vaccine

目的:研究以减毒鼠伤寒沙门菌为载体构建的幽门螺杆菌(Helicobacterpylori,Hp)疫苗的免疫保护机制。方法:将表达不同Hp抗原的减毒鼠伤寒沙门菌(Salmonellatyphimurium)分别免疫小鼠,免疫4周后以Hp攻击;在攻击前及攻击后5周分批处死小鼠,比较各组小鼠Hp定植密度及各项免疫指标的变化。结果:(1)和NS(Normalsalin,NS)对照组相比各免疫组的Hp定植密度显著下降。(2)和NS组相比攻击前后各免疫组血清IgG2a和胃黏膜Th1型细胞因子表达显著升高。(3)和NS组相比攻击后免疫组鼠胃黏膜出现明显的炎症反应。结论:以减毒鼠伤寒沙门菌为载体构建的重组幽门螺杆菌疫苗在小鼠体内诱导出以Th1反应为主并伴随免疫后胃炎的保护性免疫应答。

Objective:To study the protective immune response induced by attenuated Salmonella typhimurium expressing Helicobacter pylori antigens in mice.Methods:Mice were orally immunized with attenuated Salmonella typhimurium expressing different Helicobacter pylori antigens and challenged with Helicobacter pylori 4 weeks after immunization. Mice were sacrificed respectively before and 5 weeks after challenge.Gastric H.pylori density,Serum anti-H.pylori antibodies,mRNA expression of Thl-type and Th2-type cytokines in gastric mucosa and spleen,gastric inflammation before and after challenge were compared in different groups. Results: (1)Gastric H. pylori density of Salmonella immunized groups was decreased significantly when compared with normal saline control group. (2)When compared with normal saline group, serum IgG2a and mltNA expression level of Thl-type cytokines in the gastric mucosa of Salmonella immunized groups were increased significantly both before and after challenge.(3)Significant gastritis characterized by marked infiltration of lymphocyte, neutrphils and mononuclear cells was found in Salmonella immunized groups after challenge.Conclusion:Recombinant H.pylori vaccine using attenuated Salmonella typhimurium as vector can elicit a predominant Thl type protective immune response accompanied with post-immunization gastritis in mice.