Oral immunization with urease and Escherichia coli heat-labile enterotoxin is safe and immunogenic in Helicobacter pylori–infected adults

Michetti, Pierre; Kreiss, Christianna; Kotloff, Karen L.; Porta, Nadine; Blanco, J; Bachmann, Daniel; Herranz, Maribelle; Saldinger, Pierre F.; Corthésy–Theulaz, Irène; Losonsky, Genevieve A.; Nichols, Richard A.; Simon, J.; Stolte, Manfred; Ackerman, Samuel; Monath, Thomas P.; Blum, A. L.

doi:10.1016/s0016-5085(99)70063-6

Cited by 285 publications

(193 citation statements)

References 30 publications

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“…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

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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.

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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

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“…Unfortunately, it is known that an antibody response does not necessarily correlate with protection against H. pylori (7). In fact, in spite of the previously observed good immunogenicity in humans and both immunogenicity and efficacy in animals, when other H. pylori vaccines were assessed for therapeutic efficacy in humans (15,23), neither H. pylori eradication nor an amelioration of gastric pathology was achieved. It is unclear whether the failure of these attempts of therapeutic vaccination was due to the antigen (soluble urease or whole-cell vaccine), to the route of administration (oral), or to the necessity of limiting the dose of the adjuvants (E. coli heat-labile enterotoxin or its mutant LTR192G) because of their intrinsic toxicity.…”

Section: Discussionmentioning

confidence: 98%

“…Some vaccines against H. pylori have already been determined to be safe and immunogenic in humans (15,23), although in some cases unwanted side effects have been observed due to the toxicity of the adjuvant. In particular, a vaccine consisting of the same antigens used here, formulated with alum for intramuscular injection, was recently tested in H. pylori-negative human volunteers, showing high safety and immunogenicity (19,31), in agreement with the results described here in dogs.…”

Section: Discussionmentioning

confidence: 99%

Therapeutic Vaccination againstHelicobacter pyloriin the Beagle Dog Experimental Model: Safety, Immunogenicity, and Efficacy

et al. 2004

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Helicobacter pylori is a gram-negative bacterium that colonizes the human gastric mucosa causing gastritis and peptic ulcer and increasing the risk of gastric cancer. The efficacy of current antibiotic-based therapies can be limited by problems of patient compliance and increasing antibiotic resistance; the vaccine approach can overcome these limits. The present study describes the therapeutic vaccination of experimentally H. pyloriinfected beagle dogs, an animal model that reproduces several aspects of the human infection with H. pylori. The vaccine consisted of three recombinant H. pylori antigens, CagA, VacA, and NAP, formulated at different doses (10, 25, or 50 g each) with alum and administered intramuscularly either weekly or monthly. No adverse effects were observed after vaccination and a good immunoglobulin G response was generated against each of the three antigens. Bacterial colonization and gastritis were decreased after the completion of the vaccination cycle, especially in the case of the monthly immunization schedule. In conclusion, therapeutic vaccination in the beagle dog model was safe and immunogenic and was able to limit H. pylori colonization and the related gastric pathology.Helicobacter pylori is a spiral-shaped, gram-negative bacterium that infects the stomach of Ͼ50% of the population worldwide, with higher prevalence in the developing countries. H. pylori induces chronic inflammation of the stomach mucosa, causing chronic gastritis and peptic ulcer (9, 33); moreover, H. pylori infection is related to gastric mucosa-associated lymphoid tissue lymphoma (4) and to an increased risk of gastric cancer (36), as also proved in animal models (13,38).Current therapies, based on one antisecretory agent plus antibiotics, although effective in 80 to 90% of cases, face problems of patient compliance, increasing antibiotic resistance, and possible recurrence or reinfection; in spite of continuous effort to improve these treatments, no major breakthroughs have been achieved in the most recent years (30).To overcome the limits of antibiotic-based therapies, the vaccine approach has been undertaken since the last decade, leading us to identify some relevant bacterial antigens as candidates for vaccines (2). On the other hand, animal models of H. pylori infection have been developed to study the interaction between the bacterium and the host, the mechanisms of immune response to either infection or vaccination, and to determine the efficacy of both prophylactic and therapeutic vaccination (2,17,26,34). Among these animal models, that of the beagle dog reproduces several aspects of the human infection with H. pylori. In fact, in the beagle dog model, intragastric administration of H. pylori results in a long-term chronic infection, characterized by gastritis, epithelial alterations, superficial erosions, and the appearance of macroscopic follicles in the gastric mucosa, mainly in the antral region of the stomach (28,29).Most of the examples of vaccination against H. pylori in animal models reported in the...

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“…Most of the previous studies on developing diagnostic tests for detection of H. pylori infection involved analysis of urease enzyme, VacA, CagA, HspB, FlaA, FlaB and outer membrane proteins (OMPs) ( Michetti P, 1999;Zheng J et al, 2002;Cremonini et al 2004;Schumann et al 2006;Zhang et al, 2010;Chambers et al, 2013).Other bacterial components, such as heat shock protein, flagella and H. pylori adhesin (HpaA), have also been reported as pathogenic determinants (Park et al, 2006). In addition, a few unidentified antigenic bands, with molecular weights of 18, 34 and 39.5 kDa, have been reported to possess good diagnostic value (Andersen and Espersen 1992;Galmiche et al, 2000;Haas et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

Antigenic Proteins of Helicobacter pylori of Potential Diagnostic Value

Khalilpour

Agilan²,

Lee³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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Helicobacter pylori antigen was prepared from an isolate from a patient with a duodenal ulcer. Serum samples were obtained from culture-positive H. pylori infected patients with duodenal ulcers, gastric ulcers and gastritis (n=30). As controls, three kinds of sera without detectable H. pylori IgG antibodies were used: 30 from healthy individuals without history of gastric disorders, 30 from patients who were seen in the endoscopy clinic but were H. pylori culture negative and 30 from people with other diseases. OFF-GEL electrophoresis, SDS-PAGE and Western blots of individual serum samples were used to identify protein bands with good sensitivity and specificity when probed with the above sera and HRP-conjugated anti-human IgG. Four H. pylori protein bands showed good (≥ 70%) sensitivity and high specificity (98-100%) towards anti-Helicobacter IgG antibody in culturepositive patients sera and control sera, respectively. The identities of the antigenic proteins were elucidated by mass spectrometry. The relative molecular weights and the identities of the proteins, based on MALDI TOF/ TOF, were as follows: CagI (25 kDa), urease G accessory protein (25 kDa), UreB (63 kDa) and proline/pyrroline-5-carboxylate dehydrogenase (118 KDa). These identified proteins, singly and/or in combinations, may be useful for diagnosis of H. pylori infection in patients.

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Oral immunization with urease and Escherichia coli heat-labile enterotoxin is safe and immunogenic in Helicobacter pylori–infected adults

Cited by 285 publications

References 30 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

Therapeutic Vaccination againstHelicobacter pyloriin the Beagle Dog Experimental Model: Safety, Immunogenicity, and Efficacy

Antigenic Proteins of Helicobacter pylori of Potential Diagnostic Value

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