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Review

Vaccine development against Helicobacter pylori: from ideal antigens to the current landscape

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Pages 989-999 | Received 28 Feb 2021, Accepted 16 Jun 2021, Published online: 30 Jun 2021

References

  • Kao CY, Sheu BS, Wu JJ. Helicobacter pylori infection: an overview of bacterial virulence factors and pathogenesis. Biomed J. 2016;39(1):14–23.
  • Ishaq S, Nunn L. Helicobacter pylori and gastric cancer: a state of the art review. Gastroenterol Hepatol Bed Bench. 2015;8(Suppl 1):S6–S14.
  • Eaton KA, Morgan DR, Krakowka S. Motility as a factor in the colonisation of gnotobiotic piglets by Helicobacter pylori. J Med Microbiol. 1992;37(2):123–127.
  • Worku ML, Karim QN, Spencer J, et al. Chemotactic response of Helicobacter pylori to human plasma and bile. J Med Microbiol. 2004 Aug;53(Pt 8):807–811.
  • Xia R, Zhang B, Wang X, et al. Pathogenic interactions between Helicobacter pylori adhesion protein HopQ and human cell surface adhesion molecules CEACAMs in gastric epithelial cells. Iran J Basic Med Sci. 2019;22(7):710–715.
  • Alm RA, Bina J, Andrews BM, et al. Comparative genomics of Helicobacter pylori: analysis of the outer membrane protein families. Infect Immun. 2000 Jul;68(7):4155–4168.
  • Hooi JKY, Lai WY, Ng WK, et al. Global prevalence of helicobacter pylori infection: systematic review and meta-analysis. Gastroenterology. 2017;153(2):420–429.
  • Gemilyan M, Hakobyan G, Benejat L, et al. Prevalence of helicobacter pylori infection and antibiotic resistance profile in Armenia. Gut Pathog. 2019 8;11(1):28.
  • Okuda M, Lin Y, Kikuchi S. Helicobacter pylori infection in children and adolescents. Adv Exp Med Biol. 2019;1149:107–120.
  • Rothenbacher D, Bode G, Berg G, et al. Helicobacter pylori among preschool children and their parents: evidence of parent-child transmission. J Infect Dis. 1999;179(2):398–402.
  • Kayali S, Manfredi M, Gaiani F, et al. Helicobacter pylori, transmission routes and recurrence of infection: state of the art. Acta Biomed. 2018 17;89(8–S):72–76.
  • Watari J, Chen N, Amenta PS, et al. Helicobacter pylori associated chronic gastritis, clinical syndromes, precancerous lesions, and pathogenesis of gastric cancer development. World J Gastroenterol. 2014 May 14;20(18):5461–5473.
  • Ahmed S, Belayneh YM. Helicobacter pylori and duodenal ulcer: systematic review of controversies in causation. Clin Exp Gastroenterol. 2019;12:441–447.
  • Salar A. Gastric MALT lymphoma and Helicobacter pylori. Linfoma MALT gástrico y Helicobacter pylori. Med Clin (Barc). 2019;152(2):65–71.
  • Santos MLC, de Brito BB, Da Silva FAF, et al. Helicobacter pylori infection: beyond gastric manifestations. World J Gastroenterol. 2020 28;26(28):4076–4093.
  • Federico A, Gravina AG, Miranda A, et al. Eradication of Helicobacter pylori infection: which regimen first? World J Gastroenterol. 2014 21;20(3):665–672.
  • Buchy P, Ascioglu S, Buisson Y, et al. Impact of vaccines on antimicrobial resistance. Int J Infect Dis. 2020;90:188–196.
  • Sutton P, Boag JM. Status of vaccine research and development for Helicobacter pylori. Vaccine. 2019 28;37(50):7295–7299.
  • de Brito BB, Da Silva FAF, Soares AS, et al. Pathogenesis and clinical management of Helicobacter pylori gastric infection. World J Gastroenterol. 2019 7;25(37):5578–5589.
  • Smith MF Jr, Mitchell A, Li G, et al. Toll-like receptor (TLR) 2 and TLR5, but not TLR4, are required for Helicobacter pylori-induced NF-kappa B activation and chemokine expression by epithelial cells. J Biol Chem. 2003 29;278(35):32552–32560.
  • Kalkanli Tas S, Kirkik D, Tanoglu A, et al. Polymorphisms in Toll-like receptors 1, 2, 5, and 10 are associated with predisposition to Helicobacter pylori infection. Eur J Gastroenterol Hepatol. 2020;32(9):1141–1146.
  • Pachathundikandi SK, Müller A, Backert S. Inflammasome activation by helicobacter pylori and its implications for persistence and immunity. Curr Top Microbiol Immunol. 2016;397:117–131.
  • Varga MG, Peek RM. DNA transfer and toll-like receptor modulation by helicobacter pylori. Curr Top Microbiol Immunol. 2017;400:169–193.
  • Pachathundikandi SK, Tegtmeyer N, Arnold IC, et al. T4SS-dependent TLR5 activation by Helicobacter pylori infection. Nat Commun. 2019 16;10(1):5717.
  • Ansari S, Yamaoka Y. Helicobacter pylori Virulence Factor Cytotoxin-Associated Gene A (CagA)-Mediated Gastric Pathogenicity. Int J Mol Sci. 2020 8;21(19):7430.
  • Wilson KT, Ramanujam KS, Mobley HL, et al. Helicobacter pylori stimulates inducible nitric oxide synthase expression and activity in a murine macrophage cell line. Gastroenterology. 1996;111(6):1524–1533.
  • Lundgren A, Suri-Payer E, Enarsson K, et al. Helicobacter pylori-specific CD4+ CD25high regulatory T cells suppress memory T-cell responses to H. pylori in infected individuals. Infect Immun. 2003;71(4):1755–1762.
  • Lindholm C, Quiding-Järbrink M, Lönroth H, et al. Local cytokine response in Helicobacter pylori-infected subjects. Infect Immun. 1998;66(12):5964–5971.
  • Freire de Melo F, Rocha AM, Rocha GA, et al. A regulatory instead of an IL-17 T response predominates in Helicobacter pylori-associated gastritis in children. Microbes Infect. 2012;14(4):341–347.
  • Zhang S, Moise L, Moss SF. H. pylori vaccines: why we still don’t have any. Hum Vaccines. 2011;7(11):1153–1157.
  • DeLyria ES, Redline RW, Blanchard TG. Vaccination of mice against H pylori induces a strong Th-17 response and immunity that is neutrophil dependent. Gastroenterology. 2009;136(1):247–256.
  • Rocha GA, de Melo FF, Cabral MMDA, et al. Interleukin-27 is abrogated in gastric cancer, but highly expressed in other Helicobacter pylori-associated gastroduodenal diseases. Helicobacter. 2020;25(1):e12667.
  • Chaturvedi R, Cheng Y, Asim M, et al. Induction of polyamine oxidase 1 by Helicobacter pylori causes macrophage apoptosis by hydrogen peroxide release and mitochondrial membrane depolarization. J Biol Chem. 2004 17;279(38):40161–40173.
  • Oertli M, Noben M, Engler DB, et al. Helicobacter pylori γ-glutamyl transpeptidase and vacuolating cytotoxin promote gastric persistence and immune tolerance. Proc Natl Acad Sci U S A. 2013 19;110(8):3047–3052.
  • Owyang SY, Zhang M, El-Zaatari M, et al. Dendritic cell-derived TGF-β mediates the induction of mucosal regulatory T-cell response to Helicobacter infection essential for maintenance of immune tolerance in mice. Helicobacter. 2020;25(6):e12763.
  • Chichirau BE, Scheidt T, Diechler S, et al. Dissecting the Helicobacter pylori-regulated transcriptome of B cells. Pathog Dis. 2020 8;78(7):ftaa049.
  • Azadegan-Dehkordi F, Shirzad H, Ahmadi R, et al. Increased Indoleamine 2, 3-Dioxygenase expression modulates Th1/Th17/Th22 and Treg pathway in humans with Helicobacter Pylori-Infected gastric mucosa. Hum Immunol. 2020;28: S0198-8859(20)30412-2.
  • Malfertheiner P, Mégraud F, O’Morain C, et al. Current European concepts in the management of Helicobacter pylori infection--the Maastricht Consensus Report. The European Helicobacter Pylori Study Group (EHPSG). Eur J Gastroenterol Hepatol. 1997;9(1):1–2.
  • Malfertheiner P, Megraud F, O’Morain CA, et al. European Helicobacter and Microbiota Study Group and Consensus panel. Management of Helicobacter pylori infection-the Maastricht V/Florence Consensus Report. Gut. 2017;66(1):6–30.
  • Fallone CA, Chiba N, van Zanten SV, et al. The toronto consensus for the treatment of helicobacter pylori infection in adults. Gastroenterology. 2016;151(1):51–69.e14.
  • Chey WD, Leontiadis GI, Howden CW, et al. ACG clinical guideline: treatment of Helicobacter pylori infection. Am J Gastroenterol. 2018;113(7):1102.
  • Kim SE, Park MI, Park SJ, et al. Trends in Helicobacter pylori eradication rates by first-line triple therapy and related factors in eradication therapy. Korean J Intern Med. 2015;30(6):801–807.
  • Savoldi A, Carrara E, Graham DY, et al. Prevalence of antibiotic resistance in helicobacter pylori: a systematic review and meta-analysis in world health organization regions. Gastroenterology. 2018;155(5):1372–1382.
  • Ko SW, Kim YJ, Chung WC, et al. Bismuth supplements as the first-line regimen for Helicobacter pylori eradication therapy: systemic review and meta-analysis. Helicobacter. 2019;24(2):e12565.
  • Chen MJ, Chen CC, Chen YN, et al. Systematic review with meta-analysis: concomitant therapy vs. triple therapy for the first-line treatment of helicobacter pylori infection. Am J Gastroenterol. 2018;113:1444–1457.
  • Goderska K, Agudo Pena S, Alarcon T. Helicobacter pylori treatment: antibiotics or probiotics. Appl Microbiol Biotechnol. 2018;102(1):1–7.
  • Lau CS, Ward A, Chamberlain RS. Probiotics improve the efficacy of standard triple therapy in the eradication of Helicobacter pylori: a meta-analysis. Infect Drug Resist. 2016;9:275–289.
  • Da Silva FAF, de Brito BB, Santos MLC, et al. Treatment of Helicobacter pylori infection in children: a systematic review. World J Meta-Anal. 2020 August 28;8(4):292–308.
  • Michetti P. Vaccine against Helicobacter pylori: fact or fiction? Gut. 1997 Dec;41(6):728–730.
  • Michetti P, Kreiss C, Kotloff KL, et al. Oral immunization with urease and Escherichia coli heat-labile enterotoxin is safe and immunogenic in Helicobacter pylori-infected adults. Gastroenterology. 1999;116(4):804–812.
  • Keikha M, Eslami M, Yousefi B, et al. Potential antigen andidates for subunit vaccine development against Helicobacter pylori infection. J Cell Physiol. 2019;234(12):21460–21470.
  • Harris AG, Hazell SL. Localisation of Helicobacter pylori catalase in both the periplasm and cytoplasm, and its dependence on the twin-arginine target protein, KapA, for activity. FEMS Microbiol Lett. 2003;229(2):283–289.
  • Radcliff FJ, Hazell SL, Kolesnikow T, et al. Catalase, a novel antigen for Helicobacter pylori vaccination. Infect Immun. 1997;65(11):4668–4674.
  • El Khadir M, Alaoui Boukhris S, Benajah DA, et al. VacA and CagA status as biomarker of two opposite end outcomes of helicobacter pylori Infection (Gastric Cancer and Duodenal Ulcer) in a Moroccan Population. PLoS One. 2017;12(1):e0170616. Published 2017 Jan 26.
  • Keikha M, Eslami M, Yousefi B, et al. Potential antigen candidates for subunit vaccine development against Helicobacter pylori infection. J Cell Physiol. 2019;234(12):21460–21470.
  • Abadi AH, Mahdavi M, Khaledi A, et al. Study of serum bactericidal and splenic activity of Total-OMP- CagA combination from Brucella abortus and Helicobacter pylori in BALB/c mouse model. Microb Pathog. 2018;121:100–105.
  • Liu KY, Shi Y, Luo P, et al. Therapeutic efficacy of oral immunization with attenuated Salmonella typhimurium expressing Helicobacter pylori CagA, VacA and UreB fusion proteins in mice model. Vaccine. 2011;29(38):6679–6685.
  • Malfertheiner P, Schultze V, Rosenkranz B, et al. Safety and immunogenicity of an intramuscular Helicobacter pylori vaccine in noninfected volunteers: a phase I study. Gastroenterology. 2008;135(3):787–795.
  • Mahdavi J, Sondén B, Hurtig M, et al. Helicobacter pylori SabA adhesin in persistent infection and chronic inflammation. Science. 2002;297(5581):573–578.
  • Pang SS, Nguyen ST, Perry AJ, et al. The three-dimensional structure of the extracellular adhesion domain of the sialic acid-binding adhesin SabA from Helicobacter pylori. J Biol Chem. 2014;289(10):6332–6340.
  • Loguercio S, Dian C, Flagiello A, et al. In HspA from Helicobacter pylori vicinal disulfide bridges are a key determinant of domain B structure. FEBS Lett. 2008;582(23–24):3537–3541.
  • Ferrero RL, Thiberge JM, Kansau I, et al. The GroES homolog of Helicobacter pylori confers protective immunity against mucosal infection in mice. Proc Natl Acad Sci U S A. 1995;92(14):6499–6503.
  • Maier RJ, Benoit SL, Seshadri S. Nickel-binding and accessory proteins facilitating Ni-enzyme maturation in Helicobacter pylori. Biometals. 2007;20(3–4):655–664.
  • Ricci V, Giannouli M, Romano M, et al. Helicobacter pylori gamma-glutamyl transpeptidase and its pathogenic role. World J Gastroenterol. 2014;20(3):630–638.
  • Zhang X, Zhang J, Yang F, et al. A imunização com proteína de choque térmico A e γ-Glutamyl Transpeptidase induz a redução na Colonização Helicobacter pylori em camundongos. PLOS ONE. 2015;10(6):e0130391.
  • Gerhard M, Schmees C, Voland P, et al. A secreted low-molecular-weight protein from Helicobacter pylori induces cell-cycle arrest of T cells. Gastroenterology. 2005;128(5):1327–1339.
  • Khalifeh Gholi M, Kalali B, Formichella L, et al. Helicobacter pylori FliD protein is a highly sensitive and specific marker for serologic diagnosis of H. pylori infection. Int J Med Microbiol. 2013;303(8):618–623.
  • Ghasemi A, Mohammad N, Mautner J, et al. Immunization with recombinant FliD confers protection against Helicobacter pylori infection in mice. Mol Immunol. 2018;94:176–182.
  • Li X, Xing Y, Guo L, et al. Oral immunization with recombinant Lactococcus lactis delivering a multi-epitope antigen CTB-UE attenuates Helicobacter pylori infection in mice. Pathog Dis. 2014;72(1):78–86.
  • Jafari E, Mahmoodi S. Design, expression, and purification of a multi-epitope vaccine against Helicobacter Pylori based on Melittin as an adjuvant. Microb Pathog. 2021;157:104970.
  • Lv X, Yang J, Song H, et al. Therapeutic efficacy of the multi-epitope vaccine CTB-UE against Helicobacter pylori infection in a Mongolian gerbil model and its microRNA-155-associated immuno-protective mechanism. Vaccine. 2014;32(41):5343–5352.
  • Moss SF, Moise L, Lee DS, et al. HelicoVax: epitope-based therapeutic Helicobacter pylori vaccination in a mouse model. Vaccine. 2011;29(11):2085–2091.
  • Tobias J, Lebens M, Wai SN, et al. Surface expression of Helicobacter pylori HpaA adhesion antigen on Vibrio cholerae, enhanced by co-expressed enterotoxigenic Escherichia coli fimbrial antigens. Microb Pathog. 2017;105(177–84). DOI:https://doi.org/10.1016/j.micpath.2017.02.021
  • Yang J, Dai LX, Pan X, et al. Protection against Helicobacter pylori infection in BALB/c mice by oral administration of multi-epitope vaccine of CTB-UreI-UreB. Pathog Dis. 2015;73(5):ftv026.
  • Li Y, Chen Z, Ye J, et al. Antibody production and Th1-biased response induced by an Epitope vaccine composed of cholera toxin B unit and helicobacter pylori Lpp20 epitopes. Helicobacter. 2016;21(3):234–248.
  • Murdoch Children’s Research Institute. (2016) Helicobacter Therapeutic. Patent WO/2016/000022 7th Jan.
  • Murdoch Children’s Research Institute. Gastric Cancer Vaccine: A Novel Approach for Protecting Against Gastric Cancer and Helicobacter pylori-associated Disease. [cited 2020 Dec 20]. Available from: https://www.mcri.edu.au/sites/default/files/media/gastric_cancer_vaccine_3.pdf
  • Zhang HX, Qiu YY, Zhao YH, et al. Immunogenicity of oral vaccination with Lactococcus lactis derived vaccine candidate antigen (UreB) of Helicobacter pylori fused with the human interleukin 2 as adjuvant. Mol Cell Probes. 2014;28(1):25–30.
  • Guo L, Yang H, Tang F, et al. Oral immunization with a multivalent epitope-based vaccine, based on NAP, Urease, HSP60, and HpaA, provides therapeutic effect on H. pylori infection in mongolian gerbils. Front Cell Infect Microbiol. 2017;7:349. Published 2017 Aug 4.
  • Guo L, Hong D, Wang S, et al. Therapeutic protection against H. pylori Infection in mongolian gerbils by oral immunization with a tetravalent epitope-based vaccine with polysaccharide adjuvant. Front Immunol. 2019;10:1185. Published 2019 May 28.
  • Schmees C, Prinz C, Treptau T, et al. Inhibition of T-cell proliferation by Helicobacter pylori gamma-glutamyl transpeptidase. Gastroenterology. 2007;132(5):1820–1833.
  • Sutton P, Chionh YT. Why can’t we make an effective vaccine against Helicobacter pylori? Expert Rev Vaccines. 2013;12(4):433–441.
  • Zeng M, Mao XH, Li JX, et al. Efficacy, safety, and immunogenicity of an oral recombinant Helicobacter pylori vaccine in children in China: a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2015 38;6(10002):1457–1464.
  • Aebischer T, Bumann D, Epple HJ, 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(8):1065–1072.
  • Malfertheiner P, Selgrad M, Wex T, et al. Efficacy, immunogenicity, and safety of a parenteral vaccine against Helicobacter pylori in healthy volunteers challenged with a Cag-positive strain: a randomised, placebo-controlled phase 1/2 study. Lancet Gastroenterol Hepatol. 2018;3(10):698–707. PMID: 30042064.
  • Camilo V, Sugiyama T, Touati E. Pathogenesis of Helicobacter pylori infection. Helicobacter. 2017;22(Suppl 1):e12405.
  • Bagirova M, Allahverdiyev AM, Abamor ES, et al. An overview of challenges to eradication of Helicobacter pylori infection and future prospects. Eur Rev Med Pharmacol Sci. 2017;21(9):2199–2219.
  • Talebi Bezmin Abadi A. Vaccine against Helicobacter pylori: dInevitable approach. World J Gastroenterol. 2016 21;22(11):3150–3157.
  • Sun H, Yuan H, Tan R, et al. Immunodominant antigens that induce Th1 and Th17 responses protect mice against Helicobacter pylori infection. Oncotarget. 2018 3;9(15):12050–12063.
  • Wang J, Zhang Y, Zhu Y, et al. Total Synthesis and Immunological Evaluation of the Tri-d-glycero-d-manno-heptose Antigen of the Lipopolysaccharide as a Vaccine Candidate against Helicobacter pylori. Org Lett. 2020. DOI:https://doi.org/10.1021/acs.orglett.0c03105.
  • Pasala C, Chilamakuri CSR, Katari SK, et al. Epitope-driven common subunit vaccine design against H. pylori strains. J Biomol Struct Dyn. 2019;37(14):3740–3750.
  • Longet S, Abautret-Daly A, Davitt CJH, et al. An oral alpha-galactosylceramide adjuvanted Helicobacter pylori vaccine induces protective IL-1R- and IL-17R-dependent Th1 responses. NPJ Vaccines. 2019 25;4(1):45.
  • Sjökvist Ottsjö L, Flach CF, Clements J, et al. A double mutant heat-labile toxin from Escherichia coli, LT(R192G/L211A), is an effective mucosal adjuvant for vaccination against Helicobacter pylori infection. Infect Immun. 2013;81(5):1532–1540.
  • Holmgren J, Nordqvist S, Blomquist M, et al. Preclinical immunogenicity and protective efficacy of an oral Helicobacter pylori inactivated whole cell vaccine and multiple mutant cholera toxin: a novel and non-toxic mucosal adjuvant. Vaccine. 2018 1;36(41):6223–6230.
  • Song Z, Li B, Zhang Y, et al. Outer membrane vesicles of helicobacter pylori 7.13 as adjuvants promote protective efficacy against helicobacter pylori infection. Front Microbiol. 2020 23;11:1340.
  • Chen J, Zhong Y, Liu Y, et al. Parenteral immunization with a cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) adjuvanted Helicobacter pylori vaccine induces protective immunity against H. pylori infection in mice. Hum Vaccin Immunother. 2020;16(11):1–6.
  • Stubljar D, Jukic T, Ihan A. How far are we from vaccination against Helicobacter pylori infection? Expert Rev Vaccines. 2018;17(10):935–945.
  • Walduck AK, Raghavan S. Immunity and Vaccine Development Against Helicobacter pylori. Adv Exp Med Biol. 2019;1149:257–275.
  • Ikuse T, Blanchard TG, Czinn SJ. Inflammation, immunity, and vaccine development for the gastric pathogen helicobacter pylori. Curr Top Microbiol Immunol. 2019;421:1–19.

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