Effects of vaccination by a recombinant antigen ureB138 (a segment of the β-subunit of urease) against Helicobacter pylori infection

Abstract

Helicobacter pylorihas to counteract acidity during colonization in the stomach. The most important region for the enzymic activity ofH. pyloriurease, consisting of 138 aa (ureB138), was determined by a comparison of the homology of amino acid sequences, and a structural analysis, between urease ofH. pyloriand various other species. This region was expressed inEscherichia colias 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 theH. pyloriurease did not show any inhibitory effect at all. Immunohistochemical analysis indicated that the ureB138-specific pAb specifically recognized theH. pyloriinfecting human gastric tissues. The effects of vaccination of recombinant ureB138 against infection by this organism were also examined. Specific IgG and IgA antibodies againstH. pyloriurease were induced in the serum of mice immunized with ureB138. A reduction in the number of colonizingH. pyloriwas 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 againstH. pyloriinfection.