Therapeutic effects of molecularly designed antigen UREB138 for mice infected with Helicobacter pylori.
Helicobacter pylori (H. pylori) is a bacteria that is well known as the principal cause of chronic gastritis and peptic ulcer disease in humans. Because no effective vaccine has yet been established, we designed a new biomolecule as a vaccination antigen capable of preventing the infection of H. pylori. The designed biomolecule involves a 138 stretch (aa 201-aa 338 of beta-subunit of H. pylori urease), which is the functionally important region for urease activity. The region was expressed as a recombinant protein, called UREB138. The therapeutic vaccination was performed using UREB138 in mice persistently infected with H. pylori. The subcutaneous administration of UREB138 remarkably reduced the number of bacteria in the mice stomach compared with the control. Immunization with UREB138 enhanced the urease-specific IgA and IgG1 in the serum. Immunohistochemical staining for IgA in gastric mucosa showed that the number of mice positively stained with IgA was significantly higher in UREB138-immunized mice than in control mice. Furthermore, the expression of interferon-gamma mRNA in the gastric tissues with eradicated bacteria was higher than in the non-eradicated group. The combination of Th1- and Th2-mediated immunity plays a role in reducing the colonization of bacterial numbers of H. pylori.
Morihara
Fumiko
F
Fukuyama Medical Laboratory Co., Ltd., Fukuyama-City, Hiroshima, Japan.
Hifumi
Emi
E
Yamada
Manabu
M
Nishizono
Akira
A
Uda
Taizo
T
D000818:Animals; D000941:Antigens / Q000008:administration & dosage / Q000235:genetics / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000276:immunology; D005260:Female; D005753:Gastric Mucosa / Q000276:immunology / Q000382:microbiology; D015870:Gene Expression / Q000276:immunology; D016481:Helicobacter Infections / Q000276:immunology / Q000628:therapy*; D016480:Helicobacter pylori / Q000201:enzymology / Q000276:immunology; D006801:Humans; D007114:Immunization; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007279:Injections, Subcutaneous; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D021122:Protein Subunits / Q000235:genetics / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology / Q000627:therapeutic use; D014510:Urease / Q000037:antagonists & inhibitors* / Q000276:immunology*
D000941:Antigens; D004791:Enzyme Inhibitors; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D021122:Protein Subunits; D011994:Recombinant Proteins; D007371:Interferon-gamma; D014510:Urease