Therapeutic effects of molecularly designed antigen UREB138 for mice infected with Helicobacter pylori

• Published in: Biotechnology and bioengineering 2008-07, Vol.100 (4), p.634-643
• Main Authors: Morihara, Fumiko, Hifumi, Emi, Yamada, Manabu, Nishizono, Akira, Uda, Taizo
• Format: Article
• Language: English
• Subjects: Animals; antibacterial; Antigens - administration & dosage; Antigens - genetics; Antigens - therapeutic use; Bacteria; Biological and medical sciences; Biotechnology; Disease Models, Animal; Effects; Enzyme Inhibitors - immunology; Female; Fundamental and applied biological sciences. Psychology; Gastric Mucosa - immunology; Gastric Mucosa - microbiology; Gene Expression - immunology; Helicobacter Infections - immunology; Helicobacter Infections - therapy; Helicobacter pylori; Helicobacter pylori - enzymology; Helicobacter pylori - immunology; Humans; immune response; Immunization; immunochemistry; Immunoglobulin A - blood; Immunoglobulin G - blood; infection; inflammation; Injections, Subcutaneous; Interferon-gamma - genetics; Interferon-gamma - immunology; Mice; Mice, Inbred Strains; microbiology; Molecules; Protein Subunits - genetics; Protein Subunits - immunology; Proteins; Recombinant Proteins - immunology; Recombinant Proteins - therapeutic use; Rodents; Ulcers; Urease - antagonists & inhibitors; Urease - immunology
• ISSN: 0006-3592; 1097-0290
• DOI: 10.1002/bit.21804

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 β-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. Biotechnol. Bioeng. 2008;100: 634-643.