Liu Xiao-Feng, Hu Jia-Lu, Quan Qi-Zheng, Sun Zi-Qin, Wang Yao-Jun, Qi Feng
Department of Gastroenterology, General Hospital of Jinan Military Command Area, Jinan 250031, Shandong Province, China.
World J Gastroenterol. 2005 Apr 14;11(14):2154-6. doi: 10.3748/wjg.v11.i14.2154.
To evaluate whether attenuated Salmonella typhimurium producing Helicobacter pylori (H pylori) urease subunit B (UreB) could induce systemic immune responses against H pylori infection.
Attenuated S. typhimurium SL3261 was used as a live carrier of plasmid pTC01-UreB, which encodes recombinant H pylori UreB protein. Balb/c mice were given oral immunization with two doses of SL3261/pTC01-UreB at a 3-wk interval. Twelve weeks after oral immunization of mice, serum IgG antibodies were evaluated by ELISA assay. Gamma interferon (IFN-gamma) and interleukin 10 (IL-10) in the supernatant of spleen cell culture were also assessed by ELISA.
After oral immunization of mice, serum specific IgG antibodies against UreB in vaccine group were much higher than that in PBS and native Salmonella SL3261 control groups (A450, 0.373+/-0.100 vs 0.053+/-0.022, 0.142+/-0.039, respectively, P<0.01). Moreover, IFN-gamma in vaccine group was on average 167.53+/-29.93 pg/mL, which showed a significant increase vs that of PBS control group (35.68+/-3.55 pg/mL, P<0.01). There was also a tremendous increase of IL-10 in vaccine group compared to PBS and SL3261 control groups (275.13+/-27.65 pg/mL vs 56.00+/-7.15 pg/mL, 68.02+/-15.03 pg/mL, respectively, P<0.01). In addition, no obvious side effects in mice and no change in gastric inflammation were observed.
The multiple oral immunizations with the attenuated S. typhimurium expressing H pylori UreB could induce significant systemic immune responses, suggesting it may be used as oral vaccine against H pylori infection.
评估产幽门螺杆菌(H pylori)脲酶亚基B(UreB)的减毒鼠伤寒沙门氏菌能否诱导针对幽门螺杆菌感染的全身免疫反应。
减毒鼠伤寒沙门氏菌SL3261用作质粒pTC01-UreB的活载体,该质粒编码重组幽门螺杆菌UreB蛋白。以3周的间隔给Balb/c小鼠口服两剂SL3261/pTC01-UreB进行免疫。小鼠口服免疫12周后,通过ELISA法评估血清IgG抗体。还通过ELISA评估脾细胞培养上清液中的γ干扰素(IFN-γ)和白细胞介素10(IL-10)。
小鼠口服免疫后,疫苗组中针对UreB的血清特异性IgG抗体远高于PBS对照组和天然沙门氏菌SL3261对照组(A450分别为0.373±0.100 vs 0.053±0.022、0.142±0.039,P<0.01)。此外,疫苗组中的IFN-γ平均为167.53±29.93 pg/mL,与PBS对照组(35.68±3.55 pg/mL,P<0.01)相比有显著增加。与PBS和SL3261对照组相比,疫苗组中的IL-10也有大幅增加(分别为275.13±27.65 pg/mL vs 56.00±7.15 pg/mL、68.02±15.03 pg/mL,P<0.01)。此外,未观察到小鼠有明显副作用,胃部炎症也无变化。
用表达幽门螺杆菌UreB的减毒鼠伤寒沙门氏菌多次口服免疫可诱导显著的全身免疫反应,表明其可能用作抗幽门螺杆菌感染的口服疫苗。