Immunization with attenuated Salmonella typhimurium producing catalase in protection against gastric Helicobacter pylori infection in mice.
OBJECTIVE
To evaluate the protective effect of live attenuated Salmonella typhimurium expressing catalase against gastric Helicobacter pylori infection in mice, and to explore the underlying mechanisms of the protective immune reaction.


METHODS
The H. pylori catalase gene was introduced into attenuated S. typhimurium strain SL3261. C57BL/6 mice were orally immunized with the SL3261 vaccine strain expressing catalase or with SL3261 alone or phosphate-buffered saline (PBS). Mice were sacrificed 4 weeks after immunization and 5 weeks after H. pylori challenge, respectively.


RESULTS
All PBS control mice were infected. Eight of 13 (61.5%) mice immunized with the SL3261 vaccine strain and three of 14 (21%) mice immunized with SL3261 alone showed protection against H. pylori infection. Serum anti-H. pylori IgG2a levels of S. typhimurium-immunized mice were higher than those of PBS controls, both before and after H. pylori challenge, while there were no differences for IgG1 and IgA. Similarly, mRNA expression of interleukin (IL)-2, IL-12 and interferon-gamma in the gastric mucosa of S. typhimurium-immunized mice was significantly higher than that of PBS controls both before and after challenge. Moreover, S. typhimurium-immunized mice were characterized by marked infiltration of lymphocyte and mononuclear cells in the gastric mucosa after challenge. IL-4 and IL-10 were not detected in any of the three groups. IL-6 expression was increased in the PBS group compared with the S. typhimurium-immunized groups after challenge.


CONCLUSIONS
This study demonstrates that oral immunization of mice with catalase delivered by an attenuated S. typhimurium strain offers protection against H. pylori infection. This protective immunity was mediated through a predominantly Th1-type response and was associated with post-immunization gastritis.
Chen
Minhu
M
Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-Sen University, Guang Zhou, China.
Chen
Jie
J
Liao
Wenjun
W
Zhu
Senlin
S
Yu
Jun
J
Leung
Wai K
WK
Hu
Pinjin
P
Sung
Joseph J Y
JJ
D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial / Q000276:immunology; D001428:Bacterial Vaccines; D002374:Catalase / Q000378:metabolism*; D016207:Cytokines / Q000235:genetics; D005260:Female; D005753:Gastric Mucosa / Q000382:microbiology / Q000502:physiology; D005756:Gastritis / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control; D016481:Helicobacter Infections / Q000276:immunology / Q000517:prevention & control*; D016480:Helicobacter pylori / Q000276:immunology*; D007114:Immunization / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D010957:Plasmids; D012333:RNA, Messenger / Q000032:analysis; D012486:Salmonella typhimurium / Q000201:enzymology / Q000235:genetics / Q000276:immunology*; D013010:Sonication
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001428:Bacterial Vaccines; D016207:Cytokines; D012333:RNA, Messenger; D002374:Catalase