Protection of mice against Helicobacter pylori infection by oral immunization with live attenuated Salmonella typhimurium expressing bivalent UreB/HpaA antigens
- VernacularTitle:优化构建UreB/HpaA双价幽门螺杆菌减毒活菌疫苗的免疫保护作用
- Author:
Senlin ZHU
;
Minhu CHEN
;
Jie CHEN
- Publication Type:Journal Article
- Keywords:
Pylori, Helicobacter;
Vaccine;
Bivalent
- From:
Chinese Journal of Digestion
2001;0(10):-
- CountryChina
- Language:Chinese
-
Abstract:
Objective Compared with corresponding monovalent vaccine and pure vaccine vector, live attenuated Salmonella typhimurium expressing bivalent antigens of Helicobacter pylori (H. pylori) , UreB/HpaA was constructed by introducing a flexible and tenacious linker into urease subunit B (UreB) and HpaA of H. pylori and its protection against H. pylori infection in mice was then investigated. Methods UreB/hpaA fusion gene was amplified form H. pylori genomic DNA using sequence overlap extension PCR (SOE-PCR). UreB/HpaA bivalent live vaccine was constructed using attenuated Salmonella typhimurium vaccine vector SL3261, and its stability in vivo was observed in C57BL/6 mice. Evaluation of protection against H. pylori infection was performed in native female C57BL/6 mice by oral immunization with a single dose of the live SL3261 vaccine strain expressing UreB/HpaA (10 8 CFU). Results Sequencing results showed that encoding sequence (GGTGGAGGC) of three glycine residues was inserted into the position between ureB and hpaA fusion gene as an adapter. Bivalent live vaccine strain could be recovered from spleen and Peyer's patches for a longer time (at least 10 days). Bivalent live vaccine induced marked elevation of the levels of serum specific IgG1 and IgG2A in mouse. The immune protection rate of UreB and HpaA bivalent live vaccine was 77.3% (17/22). However only 50.0% (12/24) of the mice immunized with SL3261 vaccine strain expressing UreB and 43.5% (10/23) of the mice immunized with SL3261 vaccine strain expressing HpaA were completely protected against H. pylori challenge. Conclusions Oral immunization of mice with bivalent UreB/HpaA live vaccine could induce protective immunity against H. pylori , and the protection rate of bivalent vaccine appears to be higher than that of monovalent vaccine.