Study on Immunization Treatment of The Attenuated Salmonella typhimurium Strain Expressing Conservative Region of Helicobacter pylori Adhesin
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This work was supported by grants from The State 863 High Technology R & D Project of China(102-07-03-06), The National Natural Sciences Foundation of China(30270078) and Mlitary ‘ten-five’ Commanding Project (OIMA-132).

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    Abstract:

    In order to investigate the treatment efficacy and the potential mechanism of the attenuated Salmonella typhimurium strain expressing conservative region(AB) of Helicobacter pylori(Hp) adhesion X4072(pYA248-AB) in mouse model infected with Hp, the feasibility of X4072(pYA248-AB) in Hp vaccination was determined. Hp infected mouse model was established and applied in oral vaccination. The density of bacterial colonization was determined by the semi-quantitative bacterial culture assay. The T cell subsets of spleenocytes were assayed by flow cytometry (FCM) after immunization. IL-2 and IL-4 were detected through MTT. Mice sera and intestinal fluid were separatively tested for AB-specific IgG and IgA by ELISA. The results showed that after immune treatment, the eradicate rate of vaccine treatment group was 53.3%, which was significantly higher than that of other two control groups (X4072(pYA248-AB) vs X4072(pYA248) and PBS, P<0.01). The Hp colonized density of vaccination group with Hp infection was significantly lower than that of other two groups (X4072(pYA248-AB) vs X4072(pYA248) and PBS, P<0.01). Comparing the ratio of spleen CD4+/CD8+ T lymphocytic cells of the immuned mice by flow cytometer, it was found that the ratio of vaccine treatment group and mice typhoid fever germ control group were significantly higher than that of negative control group (X4072(pYA248-AB) and X4072(pYA248) vs PBS, P<0.05) respectively. In addition, the ratio of vaccine treatment was significantly higher than that of mice typhoid fever germ control group (X4072(pYA248-AB) vs X4072(pYA248), P<0.05). The further analysis of cytokine it was found that IL-2 and IL-4 of vaccine treatment group and mice typhoid fever germ control group were significantly higher than those of negative control group (X4072(pYA248-AB) and X4072(pYA248) and PBS, P<0.05) respectively, meanwhile, the IL-4 of vaccine treatment group was significantly higher than that of mice typhoid fever germ control group (X4072(pYA248) vs PBS, P<0.05). Humoral immunity analysis showed that IgA was only detected in the immune treatment group, and the IgG antibody titer of immune treatment group increased significantly than that of the other two group, and the titer reached 1∶10 000 two weeks after the second intensive immunization. By the animal experiments it is suggested that X4072(pYA248-AB)can eradicate or significantly reduce the Hp colonization on the mice stomach. The potential immune therapeutic mechanism included the increase of CD4+/CD8+ ratio, induction of Th1 and Th2 response, and production of the specific antibodies.

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BAI Yang, CHEN Ye, WANG Ji-De, CHANG Shao-Hong, ZHANG Zhao-Shan, ZHOU Dian-Yuan, ZHANG Ya-Li. Study on Immunization Treatment of The Attenuated Salmonella typhimurium Strain Expressing Conservative Region of Helicobacter pylori Adhesin[J]. Progress in Biochemistry and Biophysics,2004,31(1):65-72

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  • Received:May 19,2003
  • Revised:June 28,2003
  • Accepted:
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