Immunization with attenuated Salmonella typhimurium producing catalase in protection against gastric Helicobacter pylori infection in mice

Helicobacter. 2003 Dec;8(6):613-25. doi: 10.1111/j.1523-5378.2003.00182.x.

Abstract

Aim: 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.

Materials and 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Bacterial / blood
  • Antigens, Bacterial / immunology
  • Bacterial Vaccines
  • Catalase / metabolism*
  • Cytokines / genetics
  • Female
  • Gastric Mucosa / microbiology
  • Gastric Mucosa / physiology
  • Gastritis / immunology
  • Gastritis / microbiology
  • Gastritis / prevention & control
  • Helicobacter Infections / immunology
  • Helicobacter Infections / prevention & control*
  • Helicobacter pylori / immunology*
  • Immunization / methods*
  • Mice
  • Mice, Inbred C57BL
  • Plasmids
  • RNA, Messenger / analysis
  • Salmonella typhimurium / enzymology
  • Salmonella typhimurium / genetics
  • Salmonella typhimurium / immunology*
  • Sonication

Substances

  • Antibodies, Bacterial
  • Antigens, Bacterial
  • Bacterial Vaccines
  • Cytokines
  • RNA, Messenger
  • Catalase