Nysœter Gunnar, Erichsen Kari, Milde Anne Marita, Colás Eva, Kristoffersen Einar, Berstad Arnold
Department of Medicine, Section for Gastroenterology, Haukeland University Hospital, Bergen, Norway.
Drug Target Insights. 2007;2:221-8. doi: 10.4137/dti.s220. Epub 2007 Sep 18.
Intestinal microbiota seems to play an essential role in the development of inflammatory bowel diseases (IBD). We hypothesised that an oral vaccine based on live Salmonella typhi would be well tolerated and could even attenuate dextran sulfate sodium (DSS) induced colitis in rats, an animal model of IBD.
Nine male Wistar rats was used for an initial tolerance study, in which we used 3 dose-levels of Salmonella Ty21a, 0.5 × 10(9), 1 × 10(9), and 2 × 10(9)CFU, each dose being tested in 3 rats. Four treatment groups consisting of 8 male Wistar rats per group: 1) control group given standard food and water, 2) control group given four daily administrations of Salmonella Ty21a 1 × 10(9) CFU, 3) water with 5% DSS the last 7 days, 4) four daily administrations of Salmonella Ty21a before water with 5% DSS the last 7 days. The Salmonella Ty21a was administered by gastric gavage on day 1, 3, 5 and 16, while DSS was given with the drinking water from day 15 to 22. The animals were sacrificed and colonic tissue removed for analysis 22 days after gavage of the first vaccine dose.
The animals in the tolerance study got no signs of disease. In the treatment study, all animals receiving DSS had histologic indications of colitis, particularly in the distal part of the colon. Administration of Salmonella Ty21a had no significant effect on crypt and inflammation scores (p > 0.05).
Gastric administration of live vaccine strain Salmonella Ty21a was well tolerated, but did not provide any significant protection against development of DSS induced colitis in rats.
肠道微生物群似乎在炎症性肠病(IBD)的发展中起重要作用。我们假设基于伤寒沙门氏菌活菌的口服疫苗耐受性良好,甚至可以减轻葡聚糖硫酸钠(DSS)诱导的大鼠结肠炎,这是一种IBD动物模型。
九只雄性Wistar大鼠用于初始耐受性研究,我们使用了3个剂量水平的Ty21a沙门氏菌,即0.5×10⁹、1×10⁹和2×10⁹CFU,每个剂量在3只大鼠中进行测试。四个治疗组,每组由8只雄性Wistar大鼠组成:1)给予标准食物和水的对照组;2)给予每日四次1×10⁹CFU的Ty21a沙门氏菌的对照组;3)在最后7天给予含5%DSS的水的组;4)在最后7天给予含5%DSS的水之前每日四次给予Ty21a沙门氏菌的组。Ty21a沙门氏菌在第1、3、5和16天通过胃管给药,而DSS从第15天至22天通过饮用水给予。在首次疫苗剂量灌胃22天后处死动物并取出结肠组织进行分析。
耐受性研究中的动物没有疾病迹象。在治疗研究中,所有接受DSS的动物都有结肠炎的组织学指征,特别是在结肠远端。给予Ty21a沙门氏菌对隐窝和炎症评分没有显著影响(p>0.05)。
胃内给予活疫苗株Ty21a沙门氏菌耐受性良好,但对大鼠DSS诱导的结肠炎的发展没有提供任何显著保护。