title: Immunization with Heat Shock Protein A and γ-Glutamyl Transpeptidase Induces Reduction on the Helicobacter pylori Colonization in Mice.
abstract: The human gastric pathogen Helicobacter pylori (H. pylori) is a successful colonizer of the stomach. H. pylori infection strongly correlates with the development and progression of chronic gastritis, peptic ulcer disease, and gastric malignances. Vaccination is a promising strategy for preventing H. pylori infection. In this study, we evaluated the candidate antigens heat shock protein A (HspA) and H. pylori γ-glutamyl transpeptidase (GGT) for their effectiveness in development of subunit vaccines against H. pylori infection. rHspA, rGGT, and rHspA-GGT, a fusion protein based on HspA and GGT, were constructed and separately expressed in Escherichia coli and purified. Mice were then immunized intranasally with these proteins, with or without adjuvant. Immunized mice exhibited reduced bacterial colonization in stomach. The highest reduction in bacterial colonization was seen in mice immunized with the fusion protein rHspA-GGT when paired with the mucosal adjuvant LTB. Protection against H. pylori colonization was mediated by a strong systemic and localized humoral immune response, as well as a balanced Th1/Th2 cytokine response. In addition, immunofluorescence microscopy confirmed that rHspA-GGT specific rabbit antibodies were able to directly bind H. pylori in vitro. These results suggest antibodies are essential to the protective immunity associated with rHspA-GGT immunization. In summary, our results suggest HspA and GGT are promising vaccine candidates for protection against H. pylori infection.
authors.affiliation: Department of Clinical Hematology, Southwest Hospital, Third Military Medical University, Chongqing 400038, PR China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Zhang
authors.affiliation: National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing, 400038, PR China.
authors.forename: Jinyong
authors.initials: J
authors.lastname: Zhang
authors.affiliation: National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing, 400038, PR China.
authors.forename: Feng
authors.initials: F
authors.lastname: Yang
authors.affiliation: Department of Clinical Hematology, Southwest Hospital, Third Military Medical University, Chongqing 400038, PR China.
authors.forename: Weiru
authors.initials: W
authors.lastname: Wu
authors.affiliation: National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing, 400038, PR China.
authors.forename: Heqiang
authors.initials: H
authors.lastname: Sun
authors.affiliation: National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing, 400038, PR China.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Xie
authors.affiliation: Department of Clinical Hematology, Southwest Hospital, Third Military Medical University, Chongqing 400038, PR China.
authors.forename: Weike
authors.initials: W
authors.lastname: Si
authors.affiliation: National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing, 400038, PR China.
authors.forename: Quanming
authors.initials: Q
authors.lastname: Zou
authors.affiliation: Department of Clinical Hematology, Southwest Hospital, Third Military Medical University, Chongqing 400038, PR China.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Yang
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D001426:Bacterial Proteins / Q000008:administration & dosage* / Q000276:immunology; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D006360:Heat-Shock Proteins / Q000008:administration & dosage* / Q000276:immunology; D016480:Helicobacter pylori / Q000254:growth & development*; D008214:Lymphocytes / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000276:immunology; D005723:gamma-Glutamyltransferase / Q000008:administration & dosage* / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D001428:Bacterial Vaccines; D016207:Cytokines; D006360:Heat-Shock Proteins; C113725:HspA protein, bacteria; D011994:Recombinant Proteins; D005723:gamma-Glutamyltransferase