Helicobacter pylori: A Brief History of a Still Lacking Vaccine
Abstract
:1. Introduction
2. Vaccination against H. pylori in Animal Models
3. Non-Clinical Studies with the H. pylori Vaccine Candidates that Subsequently Underwent Clinical Trials
3.1. Urease
3.2. Neutrophil-Activating Protein (HP-NAP)
3.3. Vacuolating Cytotoxin (VacA)
3.4. Cytotoxin-Associated Gene (cagA)
3.5. Multi-Component Vaccines
4. Vaccination against H. pylori in Humans
4.1. Inactivated Whole-Cell Vaccines
4.2. Vaccination with Purified Recombinant Urease
4.3. Salmonella-Vectored Urease
4.4. Multi-Component Vaccines
5. Reasons that May Limit the Development of Vaccines against H. pylori
6. Conclusions and Perspectives
Conflicts of Interest
References
- Marshall, B.J.; Warren, J.R. Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration. Lancet 1984, 1, 1311–1315. [Google Scholar] [CrossRef]
- Goodwin, C.S.; Armstrong, J.A.; Chilvers, T.; Peters, M.; Collins, M.D.; Sly, L.; McConnel, W.; Harper, W.E.S. Transfer of Campylobacter pylori and Campylobacter mustelae to Helicobacter gen. nov. as Helicobacter pylori comb. nov. and Helicobacter mustelae comb. nov., respectively. Int. J. Syst. Bacteriol. 1989, 39, 397–405. [Google Scholar] [CrossRef]
- Goodwin, C.S.; Armstrong, J.A.; Marshall, B.J. Campylobacter pyloridis, gastritis, and peptic ulceration. J. Clin. Pathol. 1986, 39, 353–365. [Google Scholar] [CrossRef]
- Rothenbacher, D.; Brenner, H. Burden of Helicobacter pylori and H. pylori-related diseases in developed countries: Recent developments and future implications. Microbes Infect. 2003, 5, 693–703. [Google Scholar] [CrossRef]
- Frenck, R.W., Jr.; Clemens, J. Helicobacter in the developing world. Microbes Infect. 2003, 5, 705–713. [Google Scholar] [CrossRef]
- Malaty, H.M.; El-Kasabany, A.; Graham, D.Y.; Miller, C.C.; Reddy, S.G.; Srinivasan, S.R.; Yamaoka, Y.; Berenson, G.S. Age at acquisition of Helicobacter pylori infection: A follow-up study from infancy to adulthood. Lancet 2002, 359, 931–935. [Google Scholar] [CrossRef]
- Rothenbacher, D.; Winkler, M.; Gonser, T.; Adler, G.; Brenner, H. Role of infected parents in transmission of Helicobacter pylori to their children. Pediatr. Infect. Dis. J. 2002, 21, 674–679. [Google Scholar] [CrossRef]
- Parsonnet, J.; Shmuely, H.; Haggerty, T. Fecal and oral shedding of Helicobacter pylori from healthy infected adults. JAMA 1999, 282, 2240–2245. [Google Scholar] [CrossRef]
- Hegarty, J.P.; Dowd, M.T.; Baker, K.H. Occurrence of Helicobacter pylori in surface water in the United States. J. Appl. Microbiol. 1999, 87, 697–701. [Google Scholar] [CrossRef]
- Bahrami, A.R.; Rahimi, E.; Ghasemian Safaei, H. Detection of Helicobacter pylori in city water, dental units' water, and bottled mineral water in Isfahan, Iran. ScientificWorldJournal 2013, 2013, 280510. [Google Scholar]
- Rahimi, E.; Kheirabadi, E.K. Detection of Helicobacter pylori in bovine, buffalo, camel, ovine, and caprine milk in Iran. Foodborne. Pathog. Dis. 2012, 9, 453–456. [Google Scholar] [CrossRef]
- Sontag, S.J. Guilty as charged: bugs and drugs in gastric ulcer. Am. J. Gastroenterol. 1997, 92, 1255–1261. [Google Scholar]
- Du, M.Q.; Isaccson, P.G. Gastric MALT lymphoma: From aetiology to treatment. Lancet Oncol. 2002, 3, 97–104. [Google Scholar] [CrossRef]
- Uemura, N.; Okamoto, S.; Yamamoto, S.; Matsumura, N.; Yamaguchi, S.; Yamakido, M.; Taniyama, K.; Sasaki, N.; Schlemper, R.J. Helicobacter pylori infection and the development of gastric cancer. N. Engl. J. Med. 2001, 345, 784–789. [Google Scholar] [CrossRef]
- Konturek, P.C.; Konturek, S.J.; Brzozowski, T. Helicobacter pylori infection in gastric cancerogenesis. J. Physiol. Pharmacol. 2009, 60, 3–21. [Google Scholar]
- International Agency for Research on Cancer, World Health Organization. Schistosomes, liver flukes and Helicobacter pylori. In IARC Monographs on Evaluation of Carcinogenic Risks to Humans; IARC Press: Lyon, France, 1994; Volume 60, p. 177. [Google Scholar]
- Herrera, V.; Parsonnet, J. Helicobacter pylori and gastric adenocarcinoma. Clin. Microbiol. Infect. 2009, 15, 971–976. [Google Scholar] [CrossRef]
- IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Biological agents. Volume 100 B. A review of human carcinogens. IARC Monogr. Eval. Carcinog. Risks Hum. 2012, 100, (Pt B). 1–441. [Google Scholar]
- D'Elios, M.M.; Bergman, M.P.; Amedei, A.; Appelmelk, B.J.; Del Prete, G. Helicobacter pylori and gastric autoimmunity. Microbes Infect. 2004, 6, 1395–1401. [Google Scholar] [CrossRef]
- Bergman, M.P.; D'Elios, M.M. Cytotoxic T cells in H. pylori-related gastric autoimmunity and gastric lymphoma. J. Biomed. Biotechnol. 2010, 2010, 104918. [Google Scholar]
- Ong, S.P.; Duggan, A. Eradication of Helicobacter pylori in clinical situations. Clin. Exp. Med. 2004, 4, 30–38. [Google Scholar] [CrossRef]
- Fock, K.M.; Talley, N.; Moayyedi, P.; Hunt, R.; Azuma, T.; Sugano, K.; Xiao, S.D.; Lam, S.K.; Goh, K.L.; Chiba, T.; et al. Asia-Pacific Gastric Cancer Consensus Conference. Asia-Pacific consensus guidelines on gastric cancer prevention. J. Gastroenterol. Hepatol. 2008, 23, 351–365. [Google Scholar] [CrossRef]
- O’Connor, A.; Molina-Infante, J.; Gisbert, J.P.; O’Morain, C. Treatment of Helicobacter pylori infection 2013. Helicobacter 2013, 18 (Suppl. 1), 58–65. [Google Scholar] [CrossRef]
- Couturier, M.R.; Marshall, B.J.; Goodman, K.J.; Mégraud, F. Helicobacter pylori Diagnostics and Treatment: Could a Lack of Universal Consensus Be the Best Consensus? Clin. Chem. 2014, 60, 589–594. [Google Scholar] [CrossRef]
- Ierardi, E.; Giorgio, F.; Losurdo, G.; Di Leo, A.; Principi, M. How antibiotic resistances could change Helicobacter pylori treatment: A matter of geography? World J. Gastroenterol. 2013, 19, 8168–8180. [Google Scholar] [CrossRef]
- De Vries, A.C.; Kuipers, E.J.; Rauws, E.A. Helicobacter pylori eradication and gastric cancer: when is the horse out of the barn? Am. J. Gastroenterol. 2009, 104, 1342–1345. [Google Scholar] [CrossRef]
- Graham, D.Y.; Lu, H.; Yamaoka, Y. A report card to grade Helicobacter pylori therapy. Helicobacter 2007, 12, 275–278. [Google Scholar] [CrossRef]
- Ruggiero, P. Helicobacter pylori infection: What’s new. Curr. Opin. Infect. Dis. 2012, 25337–25344. [Google Scholar]
- Calvet, X.; Ramírez Lázaro, M.J.; Lehours, P.; Mégraud, F. Diagnosis and epidemiology of Helicobacter pylori infection. Helicobacter 2013, 18 (Suppl. 1), 5–11. [Google Scholar] [CrossRef]
- Niv, Y. H. pylori recurrence after successful eradication. World J. Gastroenterol. 2008, 14, 1477–1478. [Google Scholar] [CrossRef]
- De Vries, R.; Klok, R.M.; Brouwers, J.R.; Postma, M.J. Cost-effectiveness of a potential future Helicobacter pylori vaccine in the Netherlands: the impact of varying the discount rate for health. Vaccine 2009, 27, 846–852. [Google Scholar] [CrossRef]
- Rupnow, M.F.; Chang, A.H.; Shachter, R.D.; Owens, D.K.; Parsonnet, J. Cost-effectiveness of a potential prophylactic Helicobacter pylori vaccine in the United States. Infect. Dis. 2009, 200, 1311–1317. [Google Scholar] [CrossRef]
- Ruggiero, P.; Alloueche, A.; Rappuoli, R.; Del Giudice, G. Models for bacterial infectious diseases: Helicobacter pylori. Drug Discov. Today 2004, 1, 95–100. [Google Scholar]
- Del Giudice, G.; Malfertheiner, P.; Rappuoli, R. Development of vaccines against Helicobacter pylori. Expert Rev. Vaccines 2009, 8, 1037–1049. [Google Scholar]
- Del Giudice, G.; Covacci, A.; Telford, J.L.; Montecucco, C.; Rappuoli, R. The design of vaccines against Helicobacter pylori and their development. Annu. Rev. Immunol. 2001, 19, 523–563. [Google Scholar] [CrossRef]
- Svennerholm, A.M. Prospects for a mucosally-administered vaccine against Helicobacter pylori. Vaccine 2003, 21, 347–353. [Google Scholar] [CrossRef]
- Londono-Arcila, P.; Freeman, D.; Kleanthous, H.; O’Dowd, A.M.; Lewis, S.; Turner, A.K.; Rees, E.L.; Tibbitts, T.J.; Greenwood, J.; Monath, T.P.; et al. Attenuated Salmonella enterica serovar Typhi expressing urease effectively immunizes mice against Helicobacter pylori challenge as part of a heterologous mucosal priming-parenteral boosting vaccination regimen. Infect. Immun. 2002, 70, 5096–5106. [Google Scholar] [CrossRef]
- Vajdy, M.; Singh, M.; Ugozzoli, M.; Briones, M.; Soenawan, E.; Cuadra, L.; Kazzaz, J.; Ruggiero, P.; Peppoloni, S.; Norelli, F.; et al. Enhanced mucosal and systemic immune responses to Helicobacter pylori antigens through mucosal priming followed by systemic boosting immunizations. Immunology 2003, 110, 86–94. [Google Scholar] [CrossRef]
- Taylor, J.M.; Ziman, M.E.; Fong, J.; Solnick, J.V.; Vajdy, M. Possible correlates of long-term protection against Helicobacter pylori following systemic or combinations of mucosal and systemic immunizations. Infect. Immun. 2007, 75, 3462–3469. [Google Scholar] [CrossRef]
- Pizza, M.; Giuliani, M.M.; Fontana, M.R.; Monaci, E.; Douce, G.; Dougan, G.; Mills, K.H.; Rappuoli, R.; Del Giudice, G. Mucosal vaccines: non toxic derivatives of LT and CT as mucosal adjuvants. Vaccine 2001, 19, 2534–2541. [Google Scholar] [CrossRef]
- Appelmelk, B.J.; Negrini, R.; Moran, A.P.; Kuipers, E.J. Molecular mimicry between Helicobacter pylori and the host. Molecular mimicry between Helicobacter pylori and the host. Trends Microbiol. 1997, 5, 70–73. [Google Scholar] [CrossRef]
- Nystrom, J.; Svennerholm, A.M. Oral immunization with HpaA affords therapeutic protective immunity against H. pylori that is reflected by specific mucosal immune responses. Vaccine 2007, 25, 2591–2598. [Google Scholar] [CrossRef]
- Every, A.L.; Stent, A.; Moloney, M.B.; Ng, G.Z.; Skene, C.D.; Edwards, S.J.; Sutton, P. Evaluation of superoxide dismutase from Helicobacter pylori as a protective vaccine antigen. Vaccine 2011, 29, 1514–1518. [Google Scholar] [CrossRef]
- Kabir, S. The current status of Helicobacter pylori vaccines: A review. Helicobacter 2007, 12, 89–102. [Google Scholar] [CrossRef]
- Hongying, F.; Xianbo, W.; Fang, Y.; Yang, B.; Beiguo, L. Oral immunization with recombinant Lactobacillus acidophilus expressing the adhesin hp0410 of Helicobacter pylori induces mucosal and systemic immune responses. Clin. Vaccine Immunol. 2014, 21, 126–132. [Google Scholar] [CrossRef]
- Stent, A.; Every, A.L.; Ng, G.Z.; Chionh, Y.T.; Ong, L.S.; Edwards, S.J.; Sutton, P. Helicobacter pylori thiolperoxidase as a protective antigen in single- and multi-component vaccines. Vaccine 2012, 30, 7214–7220. [Google Scholar] [CrossRef]
- Lü, L.; Zeng, H.Q.; Wang, P.L.; Shen, W.; Xiang, T.X.; Mei, Z.C. Oral immunization with recombinant Mycobacterium smegmatis expressing the outer membrane protein 26-kilodalton antigen confers prophylactic protection against Helicobacter pylori infection. Clin. Vaccine Immunol. 2011, 18, 1957–1961. [Google Scholar] [CrossRef]
- O’Riordan, A.A.; Morales, V.A.; Mulligan, L.; Faheem, N.; Windle, H.J.; Kelleher, D.P. Alkyl hydroperoxide reductase: A candidate Helicobacter pylori vaccine. Vaccine 2012, 30, 3876–3884. [Google Scholar] [CrossRef]
- Liu, K.Y.; Shi, Y.; Luo, P.; Yu, S.; Chen, L.; Zhao, Z.; Mao, X.H.; Guo, G.; Wu, C.; Zou, Q.M. Therapeutic efficacy of oral immunization with attenuated Salmonella typhimurium expressing Helicobacter pylori CagA, VacA and UreB fusion proteins in mice model. Vaccine 2011, 29, 6679–6685. [Google Scholar] [CrossRef]
- Liu, D.S.; Hu, S.J.; Zhou, N.J.; Xie, Y.; Cao, J. Construction and characterization of recombinant attenuated Salmonella typhimurium expressing the babA2/ureI fusion gene of Helicobacter pylori. Clin. Res. Hepatol. Gastroenterol. 2011, 35, 655–660. [Google Scholar] [CrossRef]
- Guo, L.; Liu, K.; Xu, G.; Li, X.; Tu, J.; Tang, F.; Xing, Y.; Xi, T. Prophylactic and therapeutic efficacy of the epitope vaccine CTB-UA against Helicobacter pylori infection in a BALB/c mice model. Appl. Microbiol. Biotechnol. 2012, 95, 1437–1444. [Google Scholar] [CrossRef]
- Chen, J.; Lin, M.; Li, N.; Lin, L.; She, F. Therapeutic vaccination with Salmonella-delivered codon-optimized outer inflammatory protein DNA vaccine enhances protection in Helicobacter pylori infected mice. Vaccine 2012, 30, 5310–535. [Google Scholar] [CrossRef]
- Guo, L.; Liu, K.; Zhao, W.; Li, X.; Li, T.; Tang, F.; Zhang, R.; Wu, W.; Xi, T. Immunological features and efficacy of the reconstructed epitope vaccine CtUBE against Helicobacter pylori infection in BALB/c mice model. Appl. Microbiol. Biotechnol. 2013, 97, 2367–2378. [Google Scholar] [CrossRef]
- Li, H.B.; Zhang, J.Y.; He, Y.F.; Chen, L.; Li, B.; Liu, K.Y.; Yang, W.C.; Zhao, Z.; Zou, Q.M.; Wu, C. Systemic immunization with an epitope-based vaccine elicits a Th1-biased response and provides protection against Helicobacter pylori in mice. Vaccine 2012, 31, 120–126. [Google Scholar] [CrossRef]
- Huang, X.; Xu, B.; Duan, G.; Song, C. The rOmp22-HpaA fusion protein confers protective immunity against Helicobacter pylori in mice. Curr. Microbiol. 2013, 67, 487–492. [Google Scholar] [CrossRef]
- Guo, L.; Yin, R.; Liu, K.; Lv, X.; Li, Y.; Duan, X.; Chu, Y.; Xi, T.; Xing, Y. Immunological features and efficacy of a multi-epitope vaccine CTB-UE against H. pylori in BALB/c mice model. Appl. Microbiol. Biotechnol. 2014, 98, 3495–3507. [Google Scholar] [CrossRef]
- Eaton, K.A.; Brooks, C.L.; Morgan, D.R.; Krakowka, S. Essential role of urease in pathogenesis of gastritis induced by Helicobacter pylori in gnotobiotic piglets. Infect. Immun. 1991, 59, 2470–2475. [Google Scholar]
- Murakami, M.; Yoo, J.K.; Teramura, S.; Yamamoto, K.; Saita, H.; Matuo, K.; Asada, T.; Kita, T. Generation of ammonia and mucosal lesion formation following hydrolysis of urea by urease in the rat stomach. Clin. Gastroenterol. 1990, 12 (Suppl. 1), S104–S109. [Google Scholar] [CrossRef]
- Harris, P.R.; Mobley, H.L.; Perez-Perez, G.I.; Blaser, M.J.; Smith, P.D. Helicobacter pylori urease is a potent stimulus of mononuclear phagocyte activation and inflammatory cytokine production. Gastroenterology 1996, 111, 419–425. [Google Scholar] [CrossRef]
- Gobert, A.P.; Mersey, B.D.; Cheng, Y.; Blumberg, D.R.; Newton, J.C.; Wilson, K.T. Cutting edge: Urease release by Helicobacter pylori stimulates macrophage inducible nitric oxide synthase. J. Immunol. 2002, 168, 6002–6006. [Google Scholar] [CrossRef]
- 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, 107, 1002–1011. [Google Scholar]
- Marchetti, M.; Aricò, B.; Burroni, D.; Figura, N.; Rappuoli, R.; Ghiara, P. Development of a mouse model of Helicobacter pylori infection that mimics human disease. Science 1995, 267, 1655–1658. [Google Scholar] [CrossRef]
- Marchetti, M.; Rossi, M.; Giannelli, V.; Giuliani, M.M.; Pizza, M.; Censini, S.; Covacci, A.; Massari, P.; Pagliaccia, C.; Manetti, R.; et al. Protection against Helicobacter pylori infection in mice by intragastric vaccination with H. pylori antigens is achieved using a non-toxic mutant of E. coli heat-labile enterotoxin (LT) as adjuvant. Vaccine 1998, 16, 33–37. [Google Scholar] [CrossRef]
- Kleanthous, H.; Myers, G.A.; Georgakopoulos, K.M.; Tibbitts, T.J.; Ingrassia, J.W.; Gray, H.L.; Ding, R.; Zhang, Z.Z.; Lei, W.; Nichols, R.; et al. Rectal and intranasal immunizations with recombinant urease induce distinct local and serum immune responses in mice and protect against Helicobacter pylori infection. Infect. Immun. 1998, 66, 2879–2886. [Google Scholar]
- Guy, B.; Hessler, C.; Fourage, S.; Haensler, J.; Vialon-Lafay, E.; Rokbi, B.; Millet, M.J. Systemic immunization with urease protects mice against Helicobacter pylori infection. Vaccine 1998, 16, 850–856. [Google Scholar] [CrossRef]
- Corthésy-Theulaz, I.E.; Hopkins, S.; Bachmann, D.; Saldinger, P.F.; Porta, N.; Haas, R.; Yan, Z.X.; Meyer, T.; Bouzourène, H.; Blum, A.L.; et al. Mice are protected from Helicobacter pylori infection by nasal immunization with attenuated Salmonella typhimurium phoPc expressing urease A and B subunits. Infect. Immun. 1998, 66, 581–586. [Google Scholar]
- Gómez-Duarte, O.G.; Lucas, B.; Yan, Z.X.; Panthel, K.; Haas, R.; Meyer, T.F. Protection of mice against gastric colonization by Helicobacter pylori by single oral dose immunization with attenuated Salmonella typhimurium producing urease subunits A and B. Vaccine 1998, 16, 460–471. [Google Scholar] [CrossRef]
- Lee, C.K. Vaccination against Helicobacter pylori in non-human primate models and humans. Scand. J. Immunol. 2001, 53, 437–442. [Google Scholar] [CrossRef]
- Stadtländer, C.T.; Gangemi, J.D.; Khanolkar, S.S.; Kitsos, C.M.; Farris, H.E., Jr.; Fulton, L.K.; Hill, J.E.; Huntington, F.K.; Lee, C.K.; Monath, T.P. Immunogenicity and safety of recombinant Helicobacter pylori urease in a nonhuman primate. Dig. Dis. Sci. 1996, 41, 1853–1862. [Google Scholar] [CrossRef]
- Dubois, A.; Lee, C.K.; Fiala, N.; Kleanthous, H.; Mehlman, P.T.; Monath, T. Immunization against natural Helicobacter pylori infection in nonhuman primates. Infect. Immun. 1998, 66, 4340–4346. [Google Scholar]
- Lee, C.K.; Soike, K.; Hill, J.; Georgakopoulos, K.; Tibbitts, T.; Ingrassia, J.; Gray, H.; Boden, J.; Kleanthous, H.; Giannasca, P.; et al. Immunization with recombinant Helicobacter pylori urease decreases colonization levels following experimental infection of rhesus monkeys. Vaccine 1999, 17, 1493–1505. [Google Scholar] [CrossRef]
- Lee, C.K.; Soike, K.; Giannasca, P.; Hill, J.; Weltzin, R.; Kleanthous, H.; Blanchard, J.; Monath, T.P. Immunization of rhesus monkeys with a mucosal prime, parenteral boost strategy protects against infection with Helicobacter pylori. Vaccine 1999, 17, 3072–3082. [Google Scholar] [CrossRef]
- Solnick, J.V.; Canfield, D.R.; Hansen, L.M.; Torabian, S.Z. Immunization with recombinant Helicobacter pylori urease in specific-pathogen-free rhesus monkeys (Macaca. mulatta). Infect. Immun. 2000, 68, 2560–2565. [Google Scholar] [CrossRef]
- Tonello, F.; Dundon, W.G.; Satin, B.; Molinari, M.; Tognon, G.; Grandi, G.; Del Giudice, G.; Rappuoli, R.; Montecucco, C. The Helicobacter pylori neutrophil-activating protein is an iron-binding protein with dodecameric structure. Mol. Microbiol. 1999, 34, 238–246. [Google Scholar] [CrossRef]
- Montecucco, C.; De Bernard, M. Molecular and cellular mechanisms of action of the vacuolating cytotoxin (VacA) and neutrophil-activating protein (HP-NAP) virulence factors of Helicobacter pylori. Microbes Infect. 2003, 5, 715–721. [Google Scholar] [CrossRef]
- Satin, B.; Del Giudice, G.; Della Bianca, V.; Dusi, S.; Laudanna, C.; Tonello, F.; Kelleher, D.; Rappuoli, R.; Montecucco, C.; Rossi, F. The neutrophil-activating protein (HP-NAP) of Helicobacter pylori is a protective antigen and a major virulence factor. J. Exp. Med. 2000, 191, 1467–1476. [Google Scholar] [CrossRef]
- Montemurro, P.; Nishioka, H.; Dundon, W.G.; De Bernard, M.; Del Giudice, G.; Rappuoli, R.; Montecucco, C. The neutrophil-activating protein (HP-NAP) of Helicobacter pylori is a potent stimulant of mast cells. Eur. J. Immunol. 2002, 32, 671–676. [Google Scholar]
- Polenghi, A.; Bossi, F.; Fischetti, F.; Durigutto, P.; Cabrelle, A.; Tamassia, N.; Cassatela, M.A.; Montecucco, C.; Tedesco, F.; De Bernard, M. The neutrophil-activating protein of Helicobacter pylori crosses endothelia to promote neutrophil adhesion in vivo. J. Immunol. 2007, 178, 1312–1320. [Google Scholar] [CrossRef]
- De Bernard, M.; D’Elios, M.M. The immune modulating activity of the Helicobacter pylori HP-NAP: Friend or foe? Toxicon 2010, 5, 1186–1192. [Google Scholar]
- Leunk, R.D.; Johnson, P.T.; David, B.C.; Kraft, W.G.; Morgan, D.R. Cytotoxic activity in broth-culture filtrates of Campylobacter pylori. J. Med. Microbiol. 1988, 26, 93–99. [Google Scholar] [CrossRef]
- Cover, T.L.; Blaser, M.J. Purification and characterization of the vacuolating toxin from Helicobacter pylori. J. Biol. Chem. 1992, 267, 10570–10575. [Google Scholar]
- Lupetti, P.; Heuser, J.E.; Manetti, R.; Massari, P.; Lanzavecchia, S.; Bellon, P.L.; Dallai, R.; Rappuoli, R.; Telford, J.L. Oligomeric and subunit structure of the Helicobacter pylori vacuolating cytotoxin. J. Cell Biol. 1996, 133, 801–807. [Google Scholar] [CrossRef]
- Gangwer, K.A.; Mushrush, D.J.; Stauff, D.L.; Spiller, B.; McClain, M.S.; Cover, T.L.; Lacy, D.B. Crystal structure of the Helicobacter pylori vacuolating toxin p55 domain. Proc. Natl. Acad. Sci. USA 2007, 104, 16293–16298. [Google Scholar]
- Torres, V.J.; Ivie, S.E.; McClain, M.S.; Cover, T.L. Functional properties of the p33 and p55 domains of the Helicobacter pylori vacuolating cytotoxin. J. Biol. Chem. 2005, 280, 21107–21114. [Google Scholar]
- Polk, D.B.; Peek, R.M., Jr. Helicobacter pylori: gastric cancer and beyond. Nat. Rev. Cancer 2010, 10, 403–414. [Google Scholar] [CrossRef]
- Rhead, J.L.; Letley, D.P.; Mohammadi, M.; Hussein, N.; Mohagheghi, M.A.; Eshagh Hosseini, M.; Atherton, J.C. A new Helicobacter pylori vacuolating cytotoxin determinant, the intermediate region, is associated with gastric cancer. Gastroenterology 2007, 133, 926–936. [Google Scholar] [CrossRef]
- Matos, J.I.; de Sousa, H.A.; Marcos-Pinto, R.; Dinis-Ribeiro, M. Helicobacter pylori CagA and VacA genotypes and gastric phenotype: a meta-analysis. Eur. J. Gastroenterol. Hepatol. 2013, 25, 1431–1441. [Google Scholar] [CrossRef]
- Ghiara, P.; Rossi, M.; Marchetti, M.; Di Tommaso, A.; Vindigni, C.; Ciampolini, F.; Covacci, A.; Telford, J.L.; De Magistris, M.T.; Pizza, M.; et al. Therapeutic intragastric vaccination against Helicobacter pylori in mice eradicates an otherwise chronic infection and confers protection against reinfection. Infect. Immun. 1997, 65, 4996–5002. [Google Scholar]
- Ogura, K.; Maeda, S.; Nakao, M.; Watanabe, T.; Tada, M.; Kyutoku, T.; Yoshida, H.; Shiratori, Y.; Omata, M. Virulence factors of Helicobacter pylori responsible for gastric diseases in Mongolian gerbil. J. Exp. Med. 2000, 192, 1601–1610. [Google Scholar] [CrossRef]
- Parsonnet, J.; Friedman, G.D.; Orentreich, N.; Vogelman, H. Risk for gastric cancer in people with CagA positive or CagA negative Helicobacter pylori infection. Gut 1997, 40, 297–301. [Google Scholar]
- Palli, D.; Masala, G.; Del Giudice, G.; Plebani, M.; Basso, D.; Berti, D.; Numans, M.E.; Ceroti, M.; Peeters, P.H.; Bueno de Mesquita, H.B.; et al. CagA+ Helicobacter pylori infection and gastric cancer risk in the EPIC-EURGAST study. Int. J. Cancer 2007, 120, 859–867. [Google Scholar] [CrossRef]
- Blaser, M.J.; Atherton, J.C. Helicobacter pylori persistence: Biology and disease. J. Clin. Invest. 2004, 113, 321–333. [Google Scholar] [CrossRef]
- Covacci, A.; Rappuoli, R. Tyrosine-phosphorylated bacterial proteins: Trojan horses for the host cell. J. Exp. Med. 2000, 191, 587–592. [Google Scholar] [CrossRef]
- Censini, S.; Lange, C.; Xiang, Z.; Crabtree, J.E.; Ghiara, P.; Borodovsky, M.; Rappuoli, R.; Covacci, A. cag, a pathogenicity island of Helicobacter pylori, encodes type I-specific and disease-associated virulence factors. Proc. Natl. Acad. Sci. USA 1996, 93, 14648–14653. [Google Scholar] [CrossRef]
- Fischer, W. Assembly and molecular mode of action of the Helicobacter pylori Cag type IV secretion apparatus. FEBS J. 2011, 278, 1203–1212. [Google Scholar] [CrossRef]
- Terradot, L.; Waksman, G. Architecture of the Helicobacter pylori Cag-type IV secretion system. FEBS J. 2011, 278, 1213–1222. [Google Scholar] [CrossRef]
- Cendron, L.; Zanotti, G. Structural and functional aspects of unique type IV secretory components in the Helicobacter pylori cag-pathogenicity island. FEBS J. 2011, 278, 1223–1231. [Google Scholar] [CrossRef]
- Stein, M.; Rappuoli, R.; Covacci, A. Tyrosine phosphorylation of the Helicobacter pylori CagA antigen after cag-driven host cell translocation. Proc. Natl. Acad. Sci. USA 2000, 97, 1263–1268. [Google Scholar] [CrossRef]
- Kwok, T.; Zabler, D.; Urman, S.; Rohde, M.; Hartig, R.; Wessler, S.; Misselwitz, R.; Berger, J.; Sewald, N.; Konig, W.; et al. Helicobacter exploits integrin for type IV secretion and kinase activation. Nature 2007, 449, 862–866. [Google Scholar] [CrossRef]
- Kaplan-Türköz, B.; Jiménez-Soto, L.F.; Dian, C.; Ertl, C.; Remaut, H.; Louche, A.; Tosi, T.; Haas, R.; Terradot, L. Structural insights into Helicobacter pylori oncoprotein CagA interaction with β1 integrin. Proc. Natl. Acad. Sci. USA 2012, 109, 14640–14645. [Google Scholar] [CrossRef]
- Murata-Kamiya, N.; Kikuchi, K.; Hayashi, T.; Higashi, H.; Hatakeyama, M. Helicobacter pylori exploits host membrane phosphatidylserine for delivery, localization, and pathophysiological action of the CagA oncoprotein. Cell. Host Microbe 2010, 7, 399–411. [Google Scholar] [CrossRef]
- Ohnishi, N.; Yuasa, H.; Tanaka, S.; Sawa, H.; Miura, M.; Matsui, A.; Higashi, H.; Musashi, M.; Iwabuchi, K.; Suzuki, M.; et al. Transgenic expression of Helicobacter pylori CagA induces gastrointestinal and hematopoietic neoplasms in mouse. Proc. Natl. Acad. Sci. USA 2008, 105, 1003–1008. [Google Scholar] [CrossRef]
- Pacchiani, N.; Censini, S.; Buti, L.; Covacci, A. Echoes of a Distant Past: The cag Pathogenicity Island of Helicobacter pylori. Cold Spring Harb. Perspect. Med. 2013, 3, a010355. [Google Scholar] [CrossRef]
- Stein, M.; Ruggiero, P.; Rappuoli, R.; Bagnoli, F. Helicobacter pylori CagA: From Pathogenic Mechanisms to Its Use as an Anti-Cancer Vaccine. Front. Immunol. 2013, 4, 328. [Google Scholar]
- Wei, J.; Nagy, T.A.; Vilgelm, A.; Zaika, E.; Ogden, S.R.; Romero-Gallo, J.; Piazuelo, M.B.; Correa, P.; Washington, M.K.; El-Rifai, W.; et al. Regulation of p53 tumor suppressor by Helicobacter pylori in gastric epithelial cells. Gastroenterology 2010, 139, 1333–1343. [Google Scholar] [CrossRef]
- Rossi, G.; Ruggiero, P.; Peppoloni, S.; Pancotto, L.; Fortuna, D.; Lauretti, L.; Volpini, G.; Mancianti, S.; Corazza, M.; Taccini, E.; et al. Therapeutic vaccination against Helicobacter pylori in the beagle dog experimental model: safety, immunogenicity, and efficacy. Infect. Immun. 2004, 72, 3252–3259. [Google Scholar] [CrossRef]
- Rossi, G.; Rossi, M.; Vitali, C.G.; Fortuna, D.; Burroni, D.; Pancotto, L.; Capecchi, S.; Sozzi, S.; Renzoni, G.; Braca, G.; et al. A conventional beagle dog model for acute and chronic infection with Helicobacter pylori. Infect. Immun 1999, 67, 3112–3120. [Google Scholar]
- Lewis, D.J.; Huo, Z.; Barnett, S.; Kromann, I.; Giemza, R.; Galiza, E.; Woodrow, M.; Thierry-Carstensen, B.; Andersen, P.; Novicki, D.; et al. Transient facial nerve paralysis (Bell's palsy) following intranasal delivery of a genetically detoxified mutant of Escherichia coli heat labile toxin. PLoS One 2009, 4, e6999. [Google Scholar] [CrossRef]
- Graham, D.Y.; Opekun, A.R.; Osato, M.S.; El-Zimaity, H.M.; Lee, C.K.; Yamaoka, Y.; Qureshi, W.A.; Cadoz, M.; Monath, T.P. Challenge model for Helicobacter pylori infection in human volunteers. Gut 2004, 53, 1235–1243. [Google Scholar] [CrossRef]
- Moran, A.P.; Prendergast, M.M.J. Molecular mimicry in Campylobacter jejuni and Helicobacter pylori lipopolysaccharides: Contribution of gastrointestinal infections to autoimmunity. J. Autoimmun. 2001, 16, 241–256. [Google Scholar] [CrossRef]
- Kotloff, K.L.; Sztein, M.B.; Wasserman, S.S.; Losonsky, G.A.; Di Lorenzo, S.C.; Walker, R.I. Safety and immunogenicity of oral inactivated whole-cell Helicobacter pylori vaccine with adjuvant among volunteers with or without subclinical infection. Infect. Immun 2001, 69, 3581–3590. [Google Scholar]
- Losonsky, G.; Kotloff, K.L.; Walker, R.I. B cell responses in gastric antrum and duodenum following oral inactivated Helicobacter pylori whole cell (HWC) vaccine and LT(R192G) in H pylori seronegative individuals. Vaccine 2003, 21, 562–565. [Google Scholar] [CrossRef]
- Pizza, M.; Giuliani, M.M.; Fontana, M.R.; Monaci, E.; Douce, G.; Dougan, G.; Mills, K.H.; Rappuoli, R.; Del Giudice, G. Mucosal vaccines: Non toxic derivatives of LT and CT as mucosal adjuvants. Vaccine 2001, 19, 2534–2541. [Google Scholar] [CrossRef]
- Michetti, P.; Kreiss, C.; Kotloff, K.; Porta, N.; Blanco, J.L.; Bachmann, D.; Herranz, M.; Saldinger, P.F.; Corthésy-Theulaz, I.; Losonsky, G.; et al. Oral immunization with urease and Escherichia coli heat-labile enterotoxin is safe and immunogenic in Helicobacter pylori-infected adults. Gastroenterology 1999, 116, 804–812. [Google Scholar] [CrossRef]
- Banerjee, S.; Medina-Fatimi, A.; Nichols, R.; Tendler, D.; Michetti, M.; Simon, J.; Kelly, C.P.; Monath, T.P.; Michetti, P. Safety and efficacy of low dose Escherichia coli enterotoxin adjuvant for urease based oral immunisation against Helicobacter pylori in healthy volunteers. Gut 2002, 51, 634–640. [Google Scholar] [CrossRef]
- Sougioultzis, S.; Lee, C.K.; Alsahli, M.; Banerjee, S.; Cadoz, M.; Schrader, R.; Guy, B.; Bedford, P.; Monath, T.P.; Kelly, C.P.; et al. Safety and efficacy of E. coli enterotoxin adjuvant for urease-based rectal immunization against Helicobacter pylori. Vaccine 2002, 21, 194–201. [Google Scholar] [CrossRef]
- Di Petrillo, M.D.; Tibbetts, T.; Kleanthous, H.; Killeen, K.P.; Hohmann, E.L. Safety and immunogenicity of phoP/phoQ-deleted Salmonella typhi expressing Helicobacter pylori urease in adult volunteers. Vaccine 1999, 18, 449–459. [Google Scholar] [CrossRef]
- Angelakopoulos, H.; Hohmann, E.L. Pilot study of phoP/phoQ-deleted Salmonella enterica serovar typhimurium expressing Helicobacter pylori urease in adult volunteers. Infect. Immun. 2000, 68, 2135–2141. [Google Scholar] [CrossRef]
- Bumann, D.; Metzger, W.G.; Mansouri, E.; Palme, O.; Wendland, M.; Hurwitz, R. Safety and immunogenicity of live recombinant Salmonella enterica serovar Typhi Ty21a expressing urease A and B from Helicobacter pylori in human volunteers. Vaccine 2001, 20, 845–852. [Google Scholar] [CrossRef]
- Metzger, W.G.; Mansouri, E.; Kronawitter, M.; Diescher, S.; Soerensen, M.; Hurwitz, R.; Bumann, D.; Aebischer, T.; Von Specht, B.U.; Meyer, T.F. Impact of vector-priming on the immunogenicity of a live recombinant Salmonella enterica serovar typhi Ty21a vaccine expressing urease A and B from Helicobacter pylori in human volunteers. Vaccine 2004, 22, 2273–2277. [Google Scholar] [CrossRef]
- Aebischer, T.; Bumann, D.; Epple, H.J.; Metzger, W.; Schneider, T.; Cherepnev, G.; Walduck, A.K.; Kunkel, D.; Moos, V.; Loddenkemper, C.; et al. Correlation of T cell response and bacterial clearance in human volunteers challenged with Helicobacter pylori revealed by randomised controlled vaccination with Ty21a-based Salmonella vaccines. Gut 2008, 57, 1065–1072. [Google Scholar] [CrossRef]
- Xu, C.; Li, Z.S.; Du, Y.Q.; Gong, Y.F.; Yang, H.; Sun, B.; Jin, J. Construction of recombinant attenuated Salmonella typhimurium DNA vaccine expressing H. pylori ureB and IL-2. World J. Gastroenterol. 2007, 13, 939–944. [Google Scholar]
- Malfertheiner, P.; Schultze, V.; Rosenkranz, B.; Kaufmann, S.H.; Ulrichs, T.; Novicki, D.; Norelli, F.; Contorni, M.; Peppoloni, S.; Berti, D.; et al. Safety and immunogenicity of an intramuscular Helicobacter pylori vaccine in noninfected volunteers: A phase I study. Gastroenterology 2008, 135, 787–795. [Google Scholar] [CrossRef]
- Sutton, P.; Chionh, Y.T. Why can’t we make an effective vaccine against Helicobacter pylori? Expert Rev. Vaccines 2013, 12, 433–441. [Google Scholar] [CrossRef]
- Zhang, S.; Moise, L.; Moss, S.F. H. pylori vaccines: Why we still don't have any. Hum. Vaccin. 2011, 7, 1153–1157. [Google Scholar] [CrossRef]
- Salama, N.R.; Hartung, M.L.; Müller, A. Life in the human stomach: persistence strategies of the bacterial pathogen Helicobacter pylori. Nat. Rev. Microbiol. 2013, 11, 385–399. [Google Scholar] [CrossRef]
- Koch, M.; Meyer, T.F.; Moss, S.F. Inflammation, immunity, vaccines for Helicobacter pylori infection. Helicobacter 2013, 18 (Suppl. 1), 18–23. [Google Scholar] [CrossRef]
- Every, A.L. Key host-pathogen interactions for designing novel interventions against Helicobacter pylori. Trends Microbiol. 2013, 21, 253–259. [Google Scholar] [CrossRef]
- Patel, M.K.; Trombly, M.I.; Kurt-Jones, E.A. Innate immune responses to Helicobacter pylori infection: an overview. Methods Mol. Biol. 2012, 921, 205–207. [Google Scholar] [CrossRef]
- Cadamuro, A.C.; Rossi, A.F.; Maniezzo, N.M.; Silva, A.E. Helicobacter. pylori infection: host immune response, implications on gene expression and microRNAs. World. J. Gastroenterol. 2014, 20, 1424–1437. [Google Scholar] [CrossRef]
- Lee, K.; Hwang, H.; Nam, K.T. Immune Response and the Tumor Microenvironment: How They Communicate to Regulate Gastric Cancer. Gut. Liver. 2014, 8, 131–139. [Google Scholar] [CrossRef]
- Kalali, B.; Mejías-Luque, R.; Javaheri, A.; Gerhard, M. H. pylori virulence factors: influence on immune system and pathology. Mediators. Inflamm. 2014, 2014, 426309. [Google Scholar]
- Lundgren, A.; Trollmo, C.; Edebo, A.; Svennerholm, A.M.; Lundin, B.S. Helicobacter. pylori-specific CD4+ T cells home to and accumulate in the human Helicobacter. pylori-infected gastric mucosa. Infect. Immun. 2005, 73, 5612–5619. [Google Scholar] [CrossRef]
- Lundgren, A.; Strömberg, E.; Sjöling, A.; Lindholm, C.; Enarsson, K.; Edebo, A.; Johnsson, E.; Suri-Payer, E.; Larsson, P.; Rudin, A.; et al. Mucosal FOXP3-expressing CD4+CD25high regulatory T cells in Helicobacter. pylori-infected patients. Infect. Immun. 2005, 73, 523–531. [Google Scholar] [CrossRef]
- Wu, Y.Y.; Chen, J.H.; Kao, J.T.; Liu, K.C.; Lai, C.H.; Wang, Y.M.; Hsieh, C.T.; Tzen, J.T.; Hsu, P.N. Expression of CD25(high) regulatory T cells and PD-1 in gastric infiltrating CD4(+) T lymphocytes in patients with Helicobacter pylori infection. Clin. Vaccine. Immunol. 2011, 18, 1198–1201. [Google Scholar] [CrossRef]
- Müller, A.; Solnick, J.V. Inflammation, immunity, and vaccine development for Helicobacter pylori. Helicobacter 2011, 16 (Suppl. 1), 26–32. [Google Scholar] [CrossRef]
- Raghavan, S.; Quiding-Järbrink, M. Immune modulation by regulatory T cells in Helicobacter pylori-associated diseases. Endocr. Metab. Immune Disord. Drug Targets 2012, 12, 71–85. [Google Scholar] [CrossRef]
- Arnold, I.C.; Lee, J.Y.; Amieva, M.R.; Roers, A.; Flavell, R.A.; Sparwasser, T.; Müller, A. Tolerance rather than immunity protects from Helicobacter pylori-induced gastric preneoplasia. Gastroenterology 2011, 140, 199–209. [Google Scholar] [CrossRef] [Green Version]
- Atherton, J.C.; Blaser, M.J. Coadaptation of Helicobacter pylori and humans: Ancient history, modern implications. J. Clin. Invest. 2009, 119, 2475–2487. [Google Scholar] [CrossRef]
- Arnold, I.C.; Hitzler, I.; Muller, A. The immunomodulatory properties of Helicobacter pylori confer protection against allergic and chronic inflammatory disorders. Front. Cell. Infect. Microbiol. 2012, 2, 10. [Google Scholar]
- O’Connor, A.; O’Moráin, C. Helicobacter pylori infection in Europe: Current perspectives. Expert Rev. Gastroenterol. Hepatol. 2013, 7, 541–548. [Google Scholar] [CrossRef]
- Persson, C.; Canedo, P.; Machado, J.C.; El-Omar, E.M.; Forman, D. Polymorphisms in inflammatory response genes and their association with gastric cancer: A HuGE systematic review and meta-analyses. Am. J. Epidemiol. 2011, 173, 259–270. [Google Scholar] [CrossRef]
- Snaith, A.; El-Omar, E.M. Helicobacter pylori: host genetics and disease outcomes. Expert Rev. Gastroenterol. Hepatol. 2008, 2, 577–585. [Google Scholar] [CrossRef]
- Donati, C.; Rappuoli, R. Reverse vaccinology in the 21st century: Improvements over the original design. Ann. NY Acad. Sci. 2013, 1285, 115–132. [Google Scholar] [CrossRef]
- Loughlin, M.F. Using ‘omic’ technology to target Helicobacter pylori. Expert Opin. Drug Discov. 2007, 2, 1041–1051. [Google Scholar] [CrossRef]
© 2014 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
Share and Cite
Ruggiero, P.; Censini, S. Helicobacter pylori: A Brief History of a Still Lacking Vaccine. Diseases 2014, 2, 187-208. https://doi.org/10.3390/diseases2020187
Ruggiero P, Censini S. Helicobacter pylori: A Brief History of a Still Lacking Vaccine. Diseases. 2014; 2(2):187-208. https://doi.org/10.3390/diseases2020187
Chicago/Turabian StyleRuggiero, Paolo, and Stefano Censini. 2014. "Helicobacter pylori: A Brief History of a Still Lacking Vaccine" Diseases 2, no. 2: 187-208. https://doi.org/10.3390/diseases2020187