title: Subcomponent vaccine based on CTA1-DD adjuvant with incorporated UreB class II peptides stimulates protective Helicobacter pylori immunity.
abstract: A mucosal vaccine against Helicobacter pylori infection could help prevent gastric cancers and peptic ulcers. While previous attempts to develop such a vaccine have largely failed because of the requirement for safe and effective adjuvants or large amounts of well defined antigens, we have taken a unique approach to combining our strong mucosal CTA1-DD adjuvant with selected peptides from urease B (UreB). The protective efficacy of the selected peptides together with cholera toxin (CT) was first confirmed. However, CT is a strong adjuvant that unfortunately is precluded from clinical use because of its toxicity. To circumvent this problem we have developed a derivative of CT, the CTA1-DD adjuvant, that has been found safe in non-human primates and equally effective compared to CT when used intranasally. We genetically fused the selected peptides into the CTA1-DD plasmid and found after intranasal immunizations of Balb/c mice using purified CTA1-DD with 3 copies of an H. pylori urease T cell epitope (CTA1-UreB3T-DD) that significant protection was stimulated against a live challenge infection. Protection was, however, weaker than with the gold standard, bacterial lysate+CT, but considering that we only used a single epitope in nanomolar amounts the results convey optimism. Protection was associated with enhanced Th1 and Th17 immunity, but immunizations in IL-17A-deficient mice revealed that IL-17 may not be essential for protection. Taken together, we have provided evidence for the rational design of an effective mucosal subcomponent vaccine against H. pylori infection based on well selected protective epitopes from relevant antigens incorporated into the CTA1-DD adjuvant platform.
authors.affiliation: Department of Pathology, Case Western Reserve University, Cleveland, Ohio, United States of America.
authors.forename: John G
authors.initials: JG
authors.lastname: Nedrud
authors.affiliation: Department of Pathology, Case Western Reserve University, Cleveland, Ohio, United States of America.
authors.forename: Nayer
authors.initials: N
authors.lastname: Bagheri
authors.affiliation: Mucosal Immunobiology and Vaccine Research Center (MIVAC) and the Department of Microbiolgy and Immunology, Institute of Biomedicine, University of Gothenburg, Göteborg, Sweden.
authors.forename: Karin
authors.initials: K
authors.lastname: Schön
authors.affiliation: Department of Pathology, Case Western Reserve University, Cleveland, Ohio, United States of America.
authors.forename: Wei
authors.initials: W
authors.lastname: Xin
authors.affiliation: Mucosal Immunobiology and Vaccine Research Center (MIVAC) and the Department of Microbiolgy and Immunology, Institute of Biomedicine, University of Gothenburg, Göteborg, Sweden.
authors.forename: Hilda
authors.initials: H
authors.lastname: Bergroth
authors.affiliation: Mucosal Immunobiology and Vaccine Research Center (MIVAC) and the Department of Microbiolgy and Immunology, Institute of Biomedicine, University of Gothenburg, Göteborg, Sweden.
authors.forename: Dubravka Grdic
authors.initials: DG
authors.lastname: Eliasson
authors.affiliation: Mucosal Immunobiology and Vaccine Research Center (MIVAC) and the Department of Microbiolgy and Immunology, Institute of Biomedicine, University of Gothenburg, Göteborg, Sweden.
authors.forename: Nils Y
authors.initials: NY
authors.lastname: Lycke
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology*; D001428:Bacterial Vaccines / Q000008:administration & dosage* / Q000235:genetics; D002772:Cholera Toxin / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000008:administration & dosage / Q000235:genetics; D005260:Female; D016481:Helicobacter Infections / Q000276:immunology / Q000517:prevention & control; D016480:Helicobacter pylori / Q000201:enzymology* / Q000235:genetics / Q000276:immunology*; D006801:Humans; D018928:Immunity, Mucosal; D020381:Interleukin-17 / Q000172:deficiency / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology*; D014510:Urease / Q000235:genetics / Q000276:immunology*; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000235:genetics
chemical_list: D000276:Adjuvants, Immunologic; D001426:Bacterial Proteins; D001428:Bacterial Vaccines; C440610:CTA1-DD protein, recombinant; D018984:Epitopes, T-Lymphocyte; C098680:Il17a protein, mouse; D020381:Interleukin-17; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D022223:Vaccines, Subunit; D002772:Cholera Toxin; D014510:Urease