Abstract
Epitope-based vaccine is a promising strategy for therapeutic vaccination against Helicobacter pylori (H. pylori) infection. A multivalent subunit vaccine containing various antigens from H. pylori is superior to a univalent subunit vaccine. However, whether a multivalent epitope-based vaccine is superior to a univalent epitope-based vaccine in therapeutic vaccination against H. pylori, remains unclear. In this study, a multivalent epitope-based vaccine named CWAE against H. pylori urease, neutrophil-activating protein (NAP), heat shock protein 60 (HSP60) and H. pylori adhesin A (HpaA) was constructed based on mucosal adjuvant cholera toxin B subunit (CTB), Th1-type adjuvant NAP, multiple copies of selected B and Th cell epitopes (UreA27–53, UreA183–203, HpaA132–141, and HSP60189–203), and also the epitope-rich regions of urease B subunit (UreB158–251 and UreB321–385) predicted by bioinformatics. Immunological properties of CWAE vaccine were characterized in BALB/c mice model. Its therapeutic effect was evaluated in H. pylori-infected Mongolian gerbil model by comparing with a univalent epitope-based vaccine CTB-UE against H. pylori urease that was constructed in our previous studies. Both CWAE and CTB-UE could induce similar levels of specific antibodies against H. pylori urease, and had similar inhibition effect of H. pylori urease activity. However, only CWAE could induce high levels of specific antibodies to NAP, HSP60, HpaA, and also the synthetic peptides epitopes (UreB158–172, UreB181–195, UreB211–225, UreB349–363, HpaA132–141, and HSP60189–203). In addition, oral therapeutic immunization with CWAE significantly reduced the number of H. pylori colonies in the stomach of Mongolian gerbils, compared with oral immunization using CTB-UE or H. pylori urease. The protection of CWAE was associated with higher levels of mixed CD4+ T cell (Th cell) response, IgG, and secretory IgA (sIgA) antibodies to H. pylori. These results indic ate that a multivalent epitope-based vaccine including Th and B cell epitopes from various H. pylori antigens could be a promising candidate against H. pylori infection.
Highlights
Helicobacter pylori (H. pylori) is a helix-shaped bacterium that infects more than half of the world’s population (Vakil et al, 2010)
Since the CWAE vaccine showed good immunogenicity and immunological specificity, we investigated whether oral immunization with CWAE vaccine could reduce the H. pylori load in the stomachs of Mongolian gerbils infected with H. pylori, and show better therapeutic effect than cholera toxin B subunit (CTB)-UE and Urease
It has been reported that an oral recombinant subunit vaccine containing UreB and mucosal immune adjuvant LTA2B was found to be effective in H. pylorinaive children aged between 6 and 15 years, in a phase-3 clinical trial (Zeng et al, 2015)
Summary
Helicobacter pylori (H. pylori) is a helix-shaped bacterium that infects more than half of the world’s population (Vakil et al, 2010). Vaccination against H. pylori infection, especially therapeutic vaccination, could be an effective and economic strategy, either as an alternative or a complementary to antibiotic-based triple therapies. Many antigens from H. pylori, such as urease, heat shock protein 60 (HSP60), H. pylori adhesin A (HpaA) and neutrophilactivating protein (NAP), have been proved to be the excellent candidates for their ability to induce protective immune responses against H. pylori infection (Satin et al, 2000; Yamaguchi et al, 2000; Lucas et al, 2001; Flach et al, 2011; Vermoote et al, 2013). It is an effective approach to construct multivalent epitope-based vaccines by using the selected epitope peptides or the predicted epitope-rich regions, instead of using the whole antigens
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