目的建立适合不同研究需要的Hp动物模型。方法二级Wistar大鼠、二级C57BL、6小鼠及三级BALB/e小鼠40只，每种动物随机分为实验组（20只）及对照组（20只）。实验组动物接种Hp（Sydney strainl, SSI）菌液，小鼠0.4ml/只，大鼠1.5ml/只（约109/ml），连续5次，1周完成，而对照组则不作相应处理。距最后一次接种Hp的4、8、12及24周（BAIB/c16周）分别处死实验组及对照组动物各5只。取胃粘膜组织评价SSI在不同品系动物的定植及病理组织学改变。结果4周时所有实验组动物胃窦、胃体Hp检查均阳性，SSI主要定植于胃窦的胃小凹及腺腔，胃体较少；SSI定植量随感染时间的延长有增加的趋势，至24周时仍有明显定植；3种动物的Hp定植量比较，C57BL/6小鼠高于BALB/c小鼠和Wistar大鼠，对照组动物未有Hp定植。病理组织学检查：8周和24周Wistar大鼠、BALB/e和C57BL/6小鼠的胃窦及胃体出现经至中度慢性活动性胃炎改变，Wistar大鼠炎症细胞浸润的程度较BALB/e及C57BL/6小鼠重。对照组动物未见有炎症反应。结论 SSI Hp可长期定植于BALB/e、C57BL/6小鼠和Wistar大鼠腺胃，引起慢性活动性胃炎改变，上述模型的建立于Hp药物筛选、Hp疫苗的研究及Hp致病性的阐明具有重要的应用价值。

In previous studies we found that immunizing mice with a somicate of Helicobacter felis and adjuvant cholera toxin (CT; 10 ug) protected the animals against challenge with viable H. felis. The aim of this study was to determine whether a low dose of CT or its nontoxic B subunit (CTB) was effective as an adjuvant in Helicobacter oral vaceines. Significant protection against viable H. felis challenge was achieved in the amimals immunized with H. felis antigen plus the combination fo 0.5ug fo CT and 10ug fo CTB (96%), with H. felis antigen plus 0.5ug of CT (95)%, and with H. felis antigen plus 10 ug of CTB (83%), No protective effect was found in the mice immunized with either H. fells antigen alone or adjuvant CTB and CT alone. Twenty-six percent fo mice immunized with Helicobacter pylori antigen plus CT (10ug) were protected against H. fells challenge, comfimning the value of the model in predicting effects of immunization im humans. The observation that immunity can be induced with a montoxic adjuvant CTB opens the wsy for human studies with H. pylori waceines and is a further step along the road to effective strategies of prevention fo gastroduodenat diseases of major wirld signififcaace.

The common mucosal immune system was stimulated by oral immunisation with jack bean urease and the adjuvant cholera toxin. A high level of local antibody and serum antigbody was imduced in mice following hypermmunisation with thes combination No crass-reacting antibody was found against either Helicobaeter pylon or Helicobacter felis, No protection was observed against oral challenge of immunised mice with living H. felis disproving the interesting hypothesis of pallen and Clayton that plant urease might induce a protective immunity against helieobacter infection.

为构建表达HpaA蛋白的重组成减毒鼠伤寒沙门氏菌，并探讨以减毒鼠伤寒沙门氏菌为载体构建H pylori疫苗株的意义，应用PCR法从H pylori基因组DNA中扩增783bp的hpaA基因，经酶切-连接反应将其克隆入原核表达质粒pTre99A的NcoI-Sal I位点，并进行了核苷酸序列测定。重组质粒转化减毒鼠伤寒沙门氏菌SL3261，提取重组菌质粒，PCR和酶切鉴定，筛选阳性克隆。用SDS-PACE电泳和Western blot进行HpaA表达分析和鉴定，用薄层扫描分析HpaA含量。重组菌C57BL/6小鼠喂滋，分批两d和10d后处死小氧，取脾和未段回肠进行细菌培养，挑菌落提质粒鉴定。结果表明，经PCR和酶切证实，构建了含783bp hpsy基因的重组原核表达质粒，并将后者成功转化了减毒伤寒沙门氏菌。重组菌能表达约30kD HpaA蛋白，重组HpaA量约占全菌体蛋白量的38.9%，Western blot证实其有免疫反应性。小鼠重组菌喂灌两d或10d后，脾和未段回肠均发现携目的基因的菌落。这些结果提示了构建了表达H.Pylori HpaA R重组减毒鼠伤寒沙门氏菌,为制备以减毒伤寒沙门氏菌为抗原释放系统的H. pylori口康活疫苗进行了有益探索。

Helicobacter pylori is now accepted as the aetiological agent in peptic ulcer disease and has been characterised as a grade I carcinogen. The development of an effective vaccine is therefore desirable, although effective therapies for the eradication of the organism are available. The first step towards the developmetn of an anti-H. pylori vaccine was initiated by the demonstrion that a sonicate of H. felis can protect mice against infection with H. felis. Urease has been identified in the mouse model as a protective antigen. Other virulence factors, such as vacuolate cytotoxin and a heat shoek protein of H-Pylori, have been investigated as candidate vaccine components by the development of a new H. pylori mouse model. Vaccine adjuvants. delivery systems and therapeutic vaccination are likely to be the areas of major progress in the future.