Systemic immunization with urease protects mice against Helicobacter pylori infection

Guy, Bruno; Hessler, Catherine; Fourage, Sophie; Haensler, Jean; Vialon-Lafay, Elisabeth; Rokbi, Bachra; Millet, Marie-José Quentin

doi:10.1016/s0264-410x(97)00258-2

Cited by 120 publications

(108 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Urease-negative H. pylori mutants were unable to infect germ-free pigs (Eaton et al, 1991), and a urease-negative H. mustelae strain was unable to infect ferrets (Andrutis et al, 1995). Therefore, urease is considered one of the leading vaccine candidates (Michetti et al, 1999;Hirota et al, 2001;Guy et al, 1998). Lee et al (1999) showed that oral immunization against H. pylori urease significantly reduced colonization by H. pylori in rhesus monkeys.…”

Section: Resultsmentioning

confidence: 99%

Production of anti-Helicobacter pylori urease-specific immunoglobulin in egg yolk using an antigenic epitope of H. pylori urease

Shin

Roe

Kim

2004

Journal of Medical Microbiology

View full text Add to dashboard Cite

The potential therapeutic effects of Helicobacter pylori-specific immunoglobulin (IgY-Hp) derived from egg yolk and identification of the immunodominant H. pylori proteins have previously been reported. In this study, the urease epitope that is recognized by IgY-Hp was identified and used as an immunogen to produce urease-specific IgY (IgY-HpU). Epitope regions were mapped and peptides of selected epitope regions were synthesized. The IgY-Hp titre against synthetic peptides was evaluated using ELISA analysis. Hens were immunized with synthetic peptides conjugated with BSA. Urease activity was quantified by measuring the optical density of an indicator dye. Of the five synthetic peptides assayed, a peptide representing 15 amino acid residues of UreB (UB-3; aa 396-410, DNDNFRIKRYLSKYT) was specifically recognized by the IgY-Hp. Immunization of hens with BSA-conjugated UB-3 resulted in the generation of IgY-HpU. IgY-HpU markedly reduced H. pylori urease activity by 80 % as compared to control IgY (IgY-BSA). The availability of the synthetic UreBderived peptide enabled the production of highly specific anti-urease IgY, which had a significant inhibitory effect on H. pylori urease activity. Therefore, specific IgY-HpU produced using the synthetic peptide may be an effective tool against infection by H. pylori.

show abstract

Section: Resultsmentioning

confidence: 99%

Production of anti-Helicobacter pylori urease-specific immunoglobulin in egg yolk using an antigenic epitope of H. pylori urease

Shin

Roe

Kim

2004

Journal of Medical Microbiology

View full text Add to dashboard Cite

show abstract

“…For evaluation of gastritis, H&E-stained sections were scored based on the degree of infiltrating lymphocytes, plasma cells, and neutrophils (48). Grades were defined as follows: 0, none; 1, a few leukocytes scattered in the deep mucosa; 2, moderate numbers of leukocytes in the deep to mid mucosa and occasional neutrophils in gastric glands (microabscesses); 3, dense infiltrates in the deep to mid mucosa, a few microabscesses, and one or two lymphoid aggregates; and 4, dense, diffuse infiltrates throughout the lamina propria and into the submucosa, with prominent lymphoid aggregates, several microabscesses.…”

Section: Histopathologymentioning

confidence: 99%

Helicobacter pylori-Specific Antibodies Impair the Development of Gastritis, Facilitate Bacterial Colonization, and Counteract Resistance against Infection

Akhiani

Schön

Franzén

et al. 2004

The Journal of Immunology

View full text Add to dashboard Cite

In recent years, Abs have been considered a correlate rather than an effector of resistance against Helicobacter pylori infection. However, it is still poorly understood to what extent Ab production correlates with gastric immunopathology. Here we report that Abs not only are dispensable for protection, but they are detrimental to elimination of the bacteria and appear to impair gastric inflammatory responses. We found that the initial colonization with H. pylori bacteria was normal in the B cell-deficient (μMT) mice, whereas at later times (>8 wk) most of the bacteria were cleared, concomitant with the development of severe gastritis. In contrast, wild-type (WT) mice exhibited extensive bacterial colonization and only mild gastric inflammation, even at 16 wk after inoculation. Oral immunizations with H. pylori lysate and cholera toxin adjuvant stimulated comparable levels of protection in μMT and WT mice. The level of protection in both strains correlated well with the severity of the postimmunization gastritis. Thus, T cells were responsible for the gastritis, whereas Abs, including potentially host cell cross-reactive Abs, were not involved in causing the gastritis. The T cells in μMT and WT mice produced high and comparable levels of IFN-γ to recall Ag at 2 and after 8 wk, whereas IL-4 was detected after 8 wk only, indicating that Th1 activity dominated the early phase of protection, whereas later a mixed Th1 and Th2 activity was seen.

show abstract

“…For evaluation of gastritis, H&E-stained sections were scored based on the degree of infiltrating lymphocytes, plasma cells, and neutrophils (21). The scoring grades were defined as follows: 0, none; 1, a few leukocytes scattered in the deep mucosa; 2, moderate numbers of leukocytes in the deep to mid mucosa and occasional neutrophils in gastric glands (microabscesses); 3, dense infiltrates in the deep to mid mucosa, a few microabscesses, and one or two lymphoid aggregates; and 4, dense, diffuse infiltrates throughout the lamina propria and into the submucosa, frequent microabscesses, and prominent lymphoid aggregates.…”

Section: Histopathologymentioning

confidence: 99%

Vaccine-Induced Immunity againstHelicobacter pyloriInfection Is Impaired in IL-18-Deficient Mice

Akhiani

Schön

Lycke

2004

The Journal of Immunology

View full text Add to dashboard Cite

Protective immunity against Helicobacter pylori infection in mice has been associated with a strong Th1 response, involving IL-12 as well as IFN-γ, but recent studies have also demonstrated prominent eosinophilic infiltration, possibly linked to local Th2 activity in the gastric mucosa. In this study we investigated the role of IL-18, because this cytokine has been found to be a coregulator of Th1 development as well as involved in Th2-type responses with local eotaxin production that could influence gastric eosinophilia and resistance to infection. We found that IL-18−/− mice failed to develop protection after oral immunization with H. pylori lysate and cholera toxin adjuvant, indicating an important role of IL-18 in protection. Well-protected C57BL/6 wild-type (WT) mice demonstrated substantial influx of CD4+ T cells and eosinophilic cells in the gastric mucosa, whereas IL-18−/− mice had less gastritis, few CD4+ T cells, and significantly reduced numbers of eosinophilic cells. T cells in well-protected WT mice produced increased levels of IFN-γ and IL-18 to recall Ag. By contrast, unprotected IL-18−/− mice exhibited significantly reduced gastric IFN-γ and specific IgG2a Ab levels. Despite differences in gastric eosinophilic cell infiltration, protected WT and unprotected IL-18−/− mice had comparable levels of local eotaxin, suggesting that IL-18 influences protection via Th1 development and IFN-γ production rather than through promoting local production of eotaxin and eosinophilic cell infiltration.

show abstract

Systemic immunization with urease protects mice against Helicobacter pylori infection

Cited by 120 publications

References 26 publications

Production of anti-Helicobacter pylori urease-specific immunoglobulin in egg yolk using an antigenic epitope of H. pylori urease

Production of anti-Helicobacter pylori urease-specific immunoglobulin in egg yolk using an antigenic epitope of H. pylori urease

Helicobacter pylori-Specific Antibodies Impair the Development of Gastritis, Facilitate Bacterial Colonization, and Counteract Resistance against Infection

Vaccine-Induced Immunity againstHelicobacter pyloriInfection Is Impaired in IL-18-Deficient Mice

Contact Info

Product

Resources

About