Skip to main content
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1995 Jul 3;92(14):6499–6503. doi: 10.1073/pnas.92.14.6499

The GroES homolog of Helicobacter pylori confers protective immunity against mucosal infection in mice.

R L Ferrero 1, J M Thiberge 1, I Kansau 1, N Wuscher 1, M Huerre 1, A Labigne 1
PMCID: PMC41545  PMID: 7604021

Abstract

Helicobacter pylori is an important etiologic agent of gastroduodenal disease. In common with other organisms, H. pylori bacteria express heat shock proteins that share homologies with the GroES-GroEL class of proteins from Escherichia coli. We have assessed the heat shock proteins of H. pylori as potential protective antigens in a murine model of gastric Helicobacter infection. Orogastric immunization of mice with recombinant H. pylori GroES- and GroEL-like proteins protected 80% (n = 20) and 70% (n = 10) of animals, respectively, from a challenge dose of 10(4) Helicobacter felis bacteria (compared to control mice, P = 0.0042 and P = 0.0904, respectively). All mice (n = 19) that were immunized with a dual antigen preparation, consisting of H. pylori GroES-like protein and the B subunit of H. pylori urease, were protected against infection. This represented a level of protection equivalent to that provided by a sonicated Helicobacter extract (P = 0.955). Antibodies directed against the recombinant H. pylori antigens were predominantly of the IgG1 class, suggesting that a type 2 T-helper cell response was involved in protection. This work reports a protein belonging to the GroES class of heat shock proteins that was shown to induce protective immunity. In conclusion, GroES-like and urease B-subunit proteins have been identified as potential components of a future H. pylori subunit vaccine.

Full text

PDF
6502

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Austin J. W., Doig P., Stewart M., Trust T. J. Structural comparison of urease and a GroEL analog from Helicobacter pylori. J Bacteriol. 1992 Nov;174(22):7470–7473. doi: 10.1128/jb.174.22.7470-7473.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Blander S. J., Horwitz M. A. Major cytoplasmic membrane protein of Legionella pneumophila, a genus common antigen and member of the hsp 60 family of heat shock proteins, induces protective immunity in a guinea pig model of Legionnaires' disease. J Clin Invest. 1993 Feb;91(2):717–723. doi: 10.1172/JCI116253. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Blander S. J., Horwitz M. A. Vaccination with the major secretory protein of Legionella induces humoral and cell-mediated immune responses and protective immunity across different serogroups of Legionella pneumophila and different species of Legionella. J Immunol. 1991 Jul 1;147(1):285–291. [PubMed] [Google Scholar]
  4. Chen M., Lee A., Hazell S., Hu P., Li Y. Immunisation against gastric infection with Helicobacter species: first step in the prophylaxis of gastric cancer? Zentralbl Bakteriol. 1993 Sep;280(1-2):155–165. doi: 10.1016/s0934-8840(11)80952-7. [DOI] [PubMed] [Google Scholar]
  5. Chen M., Lee A., Hazell S. Immunisation against gastric helicobacter infection in a mouse/Helicobacter felis model. Lancet. 1992 May 2;339(8801):1120–1121. doi: 10.1016/0140-6736(92)90720-n. [DOI] [PubMed] [Google Scholar]
  6. Czinn S. J., Cai A., Nedrud J. G. Protection of germ-free mice from infection by Helicobacter felis after active oral or passive IgA immunization. Vaccine. 1993;11(6):637–642. doi: 10.1016/0264-410x(93)90309-l. [DOI] [PubMed] [Google Scholar]
  7. Dunn B. E., Campbell G. P., Perez-Perez G. I., Blaser M. J. Purification and characterization of urease from Helicobacter pylori. J Biol Chem. 1990 Jun 5;265(16):9464–9469. [PubMed] [Google Scholar]
  8. Dunn B. E., Roop R. M., 2nd, Sung C. C., Sharma S. A., Perez-Perez G. I., Blaser M. J. Identification and purification of a cpn60 heat shock protein homolog from Helicobacter pylori. Infect Immun. 1992 May;60(5):1946–1951. doi: 10.1128/iai.60.5.1946-1951.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Eaton K. A., Krakowka S. Chronic active gastritis due to Helicobacter pylori in immunized gnotobiotic piglets. Gastroenterology. 1992 Nov;103(5):1580–1586. doi: 10.1016/0016-5085(92)91181-3. [DOI] [PubMed] [Google Scholar]
  10. Eaton K. A., Krakowka S. Effect of gastric pH on urease-dependent colonization of gnotobiotic piglets by Helicobacter pylori. Infect Immun. 1994 Sep;62(9):3604–3607. doi: 10.1128/iai.62.9.3604-3607.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Eidt S., Stolte M. Antral intestinal metaplasia in Helicobacter pylori gastritis. Digestion. 1994;55(1):13–18. doi: 10.1159/000201116. [DOI] [PubMed] [Google Scholar]
  12. Ellis R. J., van der Vies S. M. Molecular chaperones. Annu Rev Biochem. 1991;60:321–347. doi: 10.1146/annurev.bi.60.070191.001541. [DOI] [PubMed] [Google Scholar]
  13. Elson C. O. Cholera toxin as a mucosal adjuvant: effects of H-2 major histocompatibility complex and lps genes. Infect Immun. 1992 Jul;60(7):2874–2879. doi: 10.1128/iai.60.7.2874-2879.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Evans D. J., Jr, Evans D. G., Engstrand L., Graham D. Y. Urease-associated heat shock protein of Helicobacter pylori. Infect Immun. 1992 May;60(5):2125–2127. doi: 10.1128/iai.60.5.2125-2127.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Ferrero R. L., Labigne A. Cloning, expression and sequencing of Helicobacter felis urease genes. Mol Microbiol. 1993 Jul;9(2):323–333. doi: 10.1111/j.1365-2958.1993.tb01693.x. [DOI] [PubMed] [Google Scholar]
  16. Ferrero R. L., Thiberge J. M., Huerre M., Labigne A. Recombinant antigens prepared from the urease subunits of Helicobacter spp.: evidence of protection in a mouse model of gastric infection. Infect Immun. 1994 Nov;62(11):4981–4989. doi: 10.1128/iai.62.11.4981-4989.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Hazell S. L., Mitchell H. M., Hedges M., Shi X., Hu P. J., Li Y. Y., Lee A., Reiss-Levy E. Hepatitis A and evidence against the community dissemination of Helicobacter pylori via feces. J Infect Dis. 1994 Sep;170(3):686–689. doi: 10.1093/infdis/170.3.686. [DOI] [PubMed] [Google Scholar]
  18. Hu L. T., Mobley H. L. Purification and N-terminal analysis of urease from Helicobacter pylori. Infect Immun. 1990 Apr;58(4):992–998. doi: 10.1128/iai.58.4.992-998.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Kelly S. M., Pitcher M. C., Farmery S. M., Gibson G. R. Isolation of Helicobacter pylori from feces of patients with dyspepsia in the United Kingdom. Gastroenterology. 1994 Dec;107(6):1671–1674. doi: 10.1016/0016-5085(94)90806-0. [DOI] [PubMed] [Google Scholar]
  20. Krakowka S., Morgan D. R., Kraft W. G., Leunk R. D. Establishment of gastric Campylobacter pylori infection in the neonatal gnotobiotic piglet. Infect Immun. 1987 Nov;55(11):2789–2796. doi: 10.1128/iai.55.11.2789-2796.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Labigne A., Cussac V., Courcoux P. Shuttle cloning and nucleotide sequences of Helicobacter pylori genes responsible for urease activity. J Bacteriol. 1991 Mar;173(6):1920–1931. doi: 10.1128/jb.173.6.1920-1931.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Launois P., N'Diaye M. N., Cartel J. L., Mane I., Drowart A., Van Vooren J. P., Sarthou J. L., Huygen K. Fibronectin-binding antigen 85 and the 10-kilodalton GroES-related heat shock protein are the predominant TH-1 response inducers in leprosy contacts. Infect Immun. 1995 Jan;63(1):88–93. doi: 10.1128/iai.63.1.88-93.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Lee A., Hazell S. L., O'Rourke J., Kouprach S. Isolation of a spiral-shaped bacterium from the cat stomach. Infect Immun. 1988 Nov;56(11):2843–2850. doi: 10.1128/iai.56.11.2843-2850.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Lee M. H., Pankratz H. S., Wang S., Scott R. A., Finnegan M. G., Johnson M. K., Ippolito J. A., Christianson D. W., Hausinger R. P. Purification and characterization of Klebsiella aerogenes UreE protein: a nickel-binding protein that functions in urease metallocenter assembly. Protein Sci. 1993 Jun;2(6):1042–1052. doi: 10.1002/pro.5560020617. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Li Y. Y., Hu P. J., Du G. G., Hazell S. L. The prevalence of Helicobacter pylori infection in the Peoples Republic of China. Am J Gastroenterol. 1991 Apr;86(4):446–449. [PubMed] [Google Scholar]
  26. Marshall B. J., Armstrong J. A., McGechie D. B., Glancy R. J. Attempt to fulfil Koch's postulates for pyloric Campylobacter. Med J Aust. 1985 Apr 15;142(8):436–439. doi: 10.5694/j.1326-5377.1985.tb113443.x. [DOI] [PubMed] [Google Scholar]
  27. Marshall B. J., Warren J. R. Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration. Lancet. 1984 Jun 16;1(8390):1311–1315. doi: 10.1016/s0140-6736(84)91816-6. [DOI] [PubMed] [Google Scholar]
  28. Michetti P., Corthésy-Theulaz I., Davin C., Haas R., Vaney A. C., Heitz M., Bille J., Kraehenbuhl J. P., Saraga E., Blum A. L. Immunization of BALB/c mice against Helicobacter felis infection with Helicobacter pylori urease. Gastroenterology. 1994 Oct;107(4):1002–1011. doi: 10.1016/0016-5085(94)90224-0. [DOI] [PubMed] [Google Scholar]
  29. Morris A., Nicholson G. Ingestion of Campylobacter pyloridis causes gastritis and raised fasting gastric pH. Am J Gastroenterol. 1987 Mar;82(3):192–199. [PubMed] [Google Scholar]
  30. Negrini R., Lisato L., Zanella I., Cavazzini L., Gullini S., Villanacci V., Poiesi C., Albertini A., Ghielmi S. Helicobacter pylori infection induces antibodies cross-reacting with human gastric mucosa. Gastroenterology. 1991 Aug;101(2):437–445. doi: 10.1016/0016-5085(91)90023-e. [DOI] [PubMed] [Google Scholar]
  31. Nomura A., Stemmermann G. N., Chyou P. H., Kato I., Perez-Perez G. I., Blaser M. J. Helicobacter pylori infection and gastric carcinoma among Japanese Americans in Hawaii. N Engl J Med. 1991 Oct 17;325(16):1132–1136. doi: 10.1056/NEJM199110173251604. [DOI] [PubMed] [Google Scholar]
  32. Parsonnet J., Friedman G. D., Vandersteen D. P., Chang Y., Vogelman J. H., Orentreich N., Sibley R. K. Helicobacter pylori infection and the risk of gastric carcinoma. N Engl J Med. 1991 Oct 17;325(16):1127–1131. doi: 10.1056/NEJM199110173251603. [DOI] [PubMed] [Google Scholar]
  33. Radin M. J., Eaton K. A., Krakowka S., Morgan D. R., Lee A., Otto G., Fox J. Helicobacter pylori gastric infection in gnotobiotic beagle dogs. Infect Immun. 1990 Aug;58(8):2606–2612. doi: 10.1128/iai.58.8.2606-2612.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Sharma S. A., Miller G. G., Perez-Perez G. I., Gupta R. S., Blaser M. J. Humoral and cellular immune recognition of Helicobacter pylori proteins are not concordant. Clin Exp Immunol. 1994 Jul;97(1):126–132. doi: 10.1111/j.1365-2249.1994.tb06590.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Silva C. L., Silva M. F., Pietro R. C., Lowrie D. B. Protection against tuberculosis by passive transfer with T-cell clones recognizing mycobacterial heat-shock protein 65. Immunology. 1994 Nov;83(3):341–346. [PMC free article] [PubMed] [Google Scholar]
  36. Solnick J. V., O'Rourke J., Lee A., Tompkins L. S. Molecular analysis of urease genes from a newly identified uncultured species of Helicobacter. Infect Immun. 1994 May;62(5):1631–1638. doi: 10.1128/iai.62.5.1631-1638.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Sriwanthana B., Island M. D., Maneval D., Mobley H. L. Single-step purification of Proteus mirabilis urease accessory protein UreE, a protein with a naturally occurring histidine tail, by nickel chelate affinity chromatography. J Bacteriol. 1994 Nov;176(22):6836–6841. doi: 10.1128/jb.176.22.6836-6841.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Staats H. F., Jackson R. J., Marinaro M., Takahashi I., Kiyono H., McGhee J. R. Mucosal immunity to infection with implications for vaccine development. Curr Opin Immunol. 1994 Aug;6(4):572–583. doi: 10.1016/0952-7915(94)90144-9. [DOI] [PubMed] [Google Scholar]
  39. Suerbaum S., Thiberge J. M., Kansau I., Ferrero R. L., Labigne A. Helicobacter pylori hspA-hspB heat-shock gene cluster: nucleotide sequence, expression, putative function and immunogenicity. Mol Microbiol. 1994 Dec;14(5):959–974. doi: 10.1111/j.1365-2958.1994.tb01331.x. [DOI] [PubMed] [Google Scholar]
  40. Walsh E. E. Humoral, mucosal, and cellular immune response to topical immunization with a subunit respiratory syncytial virus vaccine. J Infect Dis. 1994 Aug;170(2):345–350. doi: 10.1093/infdis/170.2.345. [DOI] [PubMed] [Google Scholar]
  41. Wotherspoon A. C., Doglioni C., Diss T. C., Pan L., Moschini A., de Boni M., Isaacson P. G. Regression of primary low-grade B-cell gastric lymphoma of mucosa-associated lymphoid tissue type after eradication of Helicobacter pylori. Lancet. 1993 Sep 4;342(8871):575–577. doi: 10.1016/0140-6736(93)91409-f. [DOI] [PubMed] [Google Scholar]
  42. van den Broek M. F., Hogervorst E. J., Van Bruggen M. C., Van Eden W., van der Zee R., van den Berg W. B. Protection against streptococcal cell wall-induced arthritis by pretreatment with the 65-kD mycobacterial heat shock protein. J Exp Med. 1989 Aug 1;170(2):449–466. doi: 10.1084/jem.170.2.449. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES