Effects of vaccination by a recombinant antigen ureB138 (a segment of the beta-subunit of urease) against Helicobacter pylori infection.
Helicobacter pylori has to counteract acidity during colonization in the stomach. The most important region for the enzymic activity of H. pylori urease, consisting of 138 aa (ureB138), was determined by a comparison of the homology of amino acid sequences, and a structural analysis, between urease of H. pylori and various other species. This region was expressed in Escherichia coli as a fusion protein with glutathione S-transferase (GST), which was cleaved by PreScission protease between the GST moiety and ureB138. The ureB138 protein was then purified by gel filtration. The polyclonal antibody (pAb) induced by immunization with the purified ureB138 could suppress urease activity by about 50 %, while the pAb against the H. pylori urease did not show any inhibitory effect at all. Immunohistochemical analysis indicated that the ureB138-specific pAb specifically recognized the H. pylori infecting human gastric tissues. The effects of vaccination of recombinant ureB138 against infection by this organism were also examined. Specific IgG and IgA antibodies against H. pylori urease were induced in the serum of mice immunized with ureB138. A reduction in the number of colonizing H. pylori was observed in mice treated with ureB138 compared to ones treated with BSA and infection control mice. In the protected mice, severe gastritis characterized by marked infiltration of mononuclear cells was noted compared with the gastritis observed in unprotected mice. Immunohistochemical staining for IgA in gastric mucosa showed that the number of mice positively stained with IgA was significantly higher in ureB138-vaccinated mice than in non-vaccinated mice. This indicates that local IgA antibody and severe post-immunization gastritis correlate well with the protection of mice against H. pylori infection.
Morihara
Fumiko
F
CREST of JST (Japan Science and Technology Corporation), 4-1-8 Hon-cho, Kawaguchi-shi, Saitama 332-0012, Japan.|Fukuyama Medical Laboratory Co. Ltd, 1-23-21 Kusado-cho, Fukuyama-shi, Hiroshima 720-8510, Japan.
Fujii
Ryoji
R
Fukuyama Medical Laboratory Co. Ltd, 1-23-21 Kusado-cho, Fukuyama-shi, Hiroshima 720-8510, Japan.
Hifumi
Emi
E
Research Center for Applied Medical Engineering, Oita University, 700 Tannohara, Oita-shi, Oita 870-1192, Japan.|Department of Life Sciences, Faculty of Bioscience and Environment, Prefectural University of Hiroshima, 562 Nanatsuka-cho, Shobara-shi, Hiroshima 727-0023, Japan.|CREST of JST (Japan Science and Technology Corporation), 4-1-8 Hon-cho, Kawaguchi-shi, Saitama 332-0012, Japan.
Nishizono
Akira
A
Department of Infectious Diseases, Faculty of Medicine, Oita University, 1-1 Idaigaoka, Hasama-machi, Yufu-shi, Oita 879-5593, Japan.|CREST of JST (Japan Science and Technology Corporation), 4-1-8 Hon-cho, Kawaguchi-shi, Saitama 332-0012, Japan.
Uda
Taizo
T
Department of Life Sciences, Faculty of Bioscience and Environment, Prefectural University of Hiroshima, 562 Nanatsuka-cho, Shobara-shi, Hiroshima 727-0023, Japan.|CREST of JST (Japan Science and Technology Corporation), 4-1-8 Hon-cho, Kawaguchi-shi, Saitama 332-0012, Japan.
D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D001428:Bacterial Vaccines / Q000235:genetics / Q000276:immunology*; D015169:Colony Count, Microbial; D004195:Disease Models, Animal; D004926:Escherichia coli / Q000235:genetics; D005260:Female; D015870:Gene Expression; D016481:Helicobacter Infections / Q000276:immunology / Q000517:prevention & control*; D016480:Helicobacter pylori / Q000276:immunology*; D006651:Histocytochemistry; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D008853:Microscopy; D021122:Protein Subunits / Q000235:genetics / Q000276:immunology; D013270:Stomach / Q000276:immunology / Q000382:microbiology; D014510:Urease / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D022223:Vaccines, Subunit / Q000235:genetics / Q000276:immunology; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology
D000907:Antibodies, Bacterial; D001428:Bacterial Vaccines; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D021122:Protein Subunits; D022223:Vaccines, Subunit; D014614:Vaccines, Synthetic; D014510:Urease