Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
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Evaluation of Factors that Can Affect Protective Immune Responses Following Oral Immunization of Recombinant Helicobacter pylori Urease Apoenzyme

  • Published : 2000.12.01
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Abstract

Helocobacter phylori is the major cause of gastritis, peptic ulcer, and a principal risk factor for gastric cancer. As the firs step towards a vaccine against H. pylori infection, Hy.pylori urease was expressed and purified as a recombinant apoenzyme (rUrease) in E. coli. In order to develop an effective immunization protocol using rUrease, the host immune responses were evaluated after the oral immunization of mice with rUrease preparations plus cholera toxin relative to various conditions, such as the physical nature of the antigen, the frequency of the booster immunization, the dose of the antigen, and the route of administration. The protective efficacy was assessed using a quantitative culture following an H. pylori SS1 challenge. It was demonstrated that rUrease, due to its particulated nature, was more superior than the UreB subunit as a vaccine antigen. The oral immunization of rUrease elicited significant systemic and secretory antibody responses, and activated predominantly Th2-type cellular responses. The bacterial colonization was significantly reduced (~100-fold) in those mice immunized with three or four weekly oran doses of rUrease plus cholera toxin (p<0.05), when compared to the non-immunized/challenged controls. The protection correlated well with the elicited secretory IgA level against rUrease, and these secretory antibody responses were highly dependent on the frequency of the booster immunization, yet unaffected by the dose of the antigen (25-200$\mu\textrm{g}$). These results demonstrate the remarkable potential of rUrease as a vaccine antigen, thereby strengthening the possibility of developing an H. pylori vaccine for humans.

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References

  1. J. Infect. Dis v.174 Density of Helicobacter pylori infection in vivo as assessed by quantitative culture and histology Atherton, J. C.;K. T. Tham;R. M. Peek;T. L. Cover;M. J. Blaser
  2. Infect. Immun. v.63 Urease-specific monoclonal antibodies prevent Helicobacter felis infectionin mice Blanchard, T. G.;S. J. Czinn;R. Maurer;W. D. Thomas;G. Soman;J. G. Nedrud
  3. Int. Arch. Allergy Appl. Immun v.75 Oral induction of the secretory antibody response by soluble and pariculate antigens Cox, D. S.;M. A. Taubman
  4. Helicobacter pylori. Infect. Immun. v.62 Effect of gastric pH on uresae-dependent colonization of gnotobiotic piglets by helicobacter pylori Eaton, K. A.;S. Krakowka
  5. J. Exp. Med. v.188 Immunization of mice with urease vaccine affords protection against Helicobacter pylori infection in the absence of antibodies and is mediated by MHC class II-restricted responses Ermak, T. H.;P. J. Giannasca;R. Nichols;G. A. Meyers;J. Nedrud;R. Weltzin;C. K. Lee;H. Kleanthous;T. P. Monath
  6. Infect. Immun. v.62 Recombinant antigens prepared from the urease subunits of Helicobacter spp.: Evidence of protection in a mouse model of gastric infection Ferrero, R. L.;J. M. Thiberge;M. Huerre;A. Labigne
  7. Proc. Natl. Acad. Sci. USA v.92 The GroES homolog of Helicobacter pylori confers protective immunity against mucosal infection in mice Ferrero, R. L.;J. M. Thiberge;I. Kansau;N. Wuscher;M. Huerre;A. Labigne
  8. J. Exp. Med. v.187 Mucosal adjuvanticity and immunogenicity of LTR72, a novel mutant of Escherichia coli heat-labile enterotoxin with partial knockout of ADP-ribosyltransferase activity Giuliani, M. M.;G. E. Giudice;V. Gianelli;G. Dougan;G. Douce;R. Rappuoli;M. Pizza
  9. Vaccine v.16 systemic immunization with urease protects mice against Helicobacter pylori infection Guy, B.;C. Hessler;S. Fourage;J. haensler;E. Vialon-Lafay;B. Rokbi;M. J. Q. Millet
  10. Infect. Immun. v.62 Induction of specific immunoglobulin A in the small intestine, colon-rectum, and vagina measured by a new method for collection of secretions from local mucosal surfaces Haneberg, B.;D. Kendall;H. M. Amerongen;F. M. Apter;J. P. Kraehenbuhl;M. R. neutra
  11. J. Gen. Microbiol. v.136 Investigation of the structure and localization of the urease of Helicobacter pylori using monoclonal antibodies Hawtin, P. R.;A. R. Stacey;D.G. Newell
  12. Infect. Immun. v.60 Purification of recombinant Helicobacter pylori urease apoenzyme encoded by ureA and ureB Hu, L. T.;P. A. Foxall;R. Russel;H. L. T. Mobley
  13. Infect. Immun. v.58 Purification and Nterminal analysis of urease from Helicobacter pylori Hu, L. T.;H. L. T. Mobley
  14. IARC Monogr. Eval. Carcinog. Risks Hum v.61 Schistosomes, liver flukes and Helicobacter pylori International Agency for Research on Cancer
  15. Am. J. Gastroenterol. v.86 New small animal model for human gastric helicobacter pylori infection: Success in both nude and euthymic mice Karita, M.;T. Kouchiyama;K. Okita;T. Nakazawa
  16. J. Microbiol. Biotechnol. v.9 Synergistic inhibition of membrane ATPase and cell growth of Helicobacter pylori by ATPase inhibitors Ki, M. R.;S. K. Yun;W. J. Lim;B. S. Hong;S. Y. Hwang
  17. Infect. Immun. v.66 Rectal and intranasal immunizations with recombinant urease induce distinct local and serum immune responses in mice and protect against Heliconacter pylori infection Kleanthous, H.;G. A. Myers;K. M. Georgkopoulos;T. J. Tibbits;J. W. Ingrassia;H. L. Gary;R. Ding;Z. Z. Zhang;W. Lei;R. Nivhols;C. K. Lee;T. H. Ermak;T. P. Monath
  18. Gastroenterology v.112 A stansardized mouse model of Helicobacter pylori infection: Introducing the Sydney strain Lee, A.;J. O'Rouke;M. C. de Ungria;B. Robertson;G. Daskalopoulos;M. F. Dixon
  19. J. Infect. Dis. v.172 Oral immunization with recombinant Helicobacter pylori urease induces secretory IgA antibodies and protects mice from challenge with Helicobacter felis Lee, C. K.;R. Weltzin;W. D. Thomas;H. Kleanthous;T. H. Ermak;G. Soman;J. E. Hill;S. K. Ackerman;T. P. Monath
  20. J. Microbiol. Biotechnol. v.8 Separate expression and in vitro activation of recombinant Helicobacter pyroli urease structural subunits Lee, K. K.;J. S. Son;Y. J. Chang;S. U. Kim;K. H. Kim
  21. J. Microbiol. Biotechnol. v.9 Lactobacillus acidophilus inhibits the Helicobacter pyroli adherence Lee, Y.;E. Shin;J. Lee;J. H. Park
  22. Scand. J. Gastroenterol. v.196(suppl.) Compliance, adverse events and antibiotic resistance in Helicobacter pylori treatment Malfertheiner, P.
  23. Science v.267 Development of a mouse model of Helicobacter pylori infection that mimics human disease Marchetti, M.;B. Arico;D. Burroni;N. Figura;R. Rappuoli;P. Ghira
  24. Vaccine v.17 Oral immunization with recombinant helicobacter pylori urease confers long-lasting immunity against Helicobacter felis infection Meyers, G. A.;T. H. Ermak;K. Geotgakopoulos;T. Tibbitts;J. Ingrassia;H. Gray;H. Kleanthous;C. K. Lee;T. P. Monath
  25. Gastroenterology v.107 Immunization of Balb/c mice against Helicobacterology Michetti, P.;I. Corthesy-Theulaz;C. Davin;R. Haas;A. C. Vaney;M. Heitz;J. Bille;J. P. Kraehenbuhl;E. Saraga;A. L. Blum
  26. Gastroenterology v.113 Murine CD4 T-cell response to Helicobacter infection: TH1 cells enhance gastritis and TH2 cells reduce bacterial load Mohammadi, M.;J. Nedrud;R. Redline;N. Lycke;S. J. Czinn
  27. Novel Delivery Systems for Oral Vaccines Oral immunization and the common mucosal immune system O'Hagan, D. T.;D. T. OHagan(ed.)
  28. Infect. Immun. v.63 Effect of oral immunization with recombinant urease on murine Helicobacter felis gastritis Pappo, J.;W. D. Thomas;Z. Kabok;N. S. Taylor;J. C. Murphy;J. G. Fox
  29. Exp. Mol. Med. v.32 The mucosal adjuvanticity of two nontoxic mutants of Escherichia coli heat-labile enterotoxin varies with immunization routes Park, E. J.;J. H. Chang;J. S. Kim;J. S. Yum;S. I. Chung
  30. Infect. Immun. v.65 Catalase, a novel antigen for Helicobacter pylori vaccination Radcliff, F. J.;S. L. hazell;T. Kolesnikow;C. Doidge;A. Lee
  31. Gut v.36 Helicobacter pylori reinfection with identical organisms: Transmission by the patients spouses Schutze, K.;E. Hentschel;B. Deagosics;A. M. Hirschl
  32. J. Microbiol. Biotechnol. v.9 Purification and characterization of the recombinant Bacillus pasteurii urease overexpressed in Escherichia coli Shin, I. S.;M. H. Lee
  33. Infect. Immun v.58 Helicobacter pylori urease activity is toxic to human gastric epithelial cells Smoot, D. T.;H. L. T. Mobley;G. R. Chippendale;J. F. Lewison;J. H. Resau
  34. Lancet v.342 Protection by human milk IgA against Helicobacter pylori infection in infancy Thomas, J. E.;S. Austin;A. Dale;P. McClean;M. Harding;W. A. Coward;L. T. Weaver
  35. Lancet v.ii Unidentified curved bacilli on gastric epithelium in active chronic gastritis Warren, J. R.;B. Marshall
  36. J. Clin. Path v.39 Local immune response to gastric Campylobacter in non-ulcer dyspepsia Watt, J. I.;B. J. Rarhbone;R. V. Heatly
  37. Vaccine v.15 Novel intransal immunization techniques for antibody induction and protection of mice against Helicobacter felis infection Weltzin, R.;H. Kleanthous;F. Guirakhoo;T. P. Monath;C. K. Lee
  38. J. Exp. Med. v.178 Helper T cell subsets for immunoglobulin a responses: Oral immunization with tetanus toxoid and cholera toxin as adjuvant selectively induces Th2 cells in mucosal associated tissues Xu-Amano, J.;H. Kiyono;R. Jackson;H. F. Staats;K. Fujihashi;P. D. Burrows;C. O. Elson;S. Pillai;J. R. McGhee