title: Glycoconjugate vaccine containing Escherichia coli O157:H7 O-antigen linked with maltose-binding protein elicits humoral and cellular responses.
abstract: Glycoconjugate is one of the most efficacious and safest vaccines against bacterial pathogens. Previous studies of glycoconjugates against pathogen E. coli O157:H7 focused more on the humoral responses they elicited. However, little was known about their cellular responses. In this study, we exploited a novel approach based on bacterial protein N-linked glycosylation system to produce glycoconjugate containing Escherichia coli O157:H7 O-antigen linked with maltose-binding protein and examined its humoral and cellular responses in BALB/c mice. The transfer of E. coli O157:H7 O-antigen to MBP was confirmed by western blot and MALDI-TOF MS. Mice injected with glycoconjugate O-Ag-MBP elicited serum bactericidal antibodies including anti-E. coli O157:H7 O-antigen IgG and IgM. Interestingly, O-Ag-MBP also stimulated the secretion of anti-E. coli O157:H7 O-antigen IgA in intestine. In addition, O-Ag-MBP stimulated cellular responses by recruiting Th1-biased CD4+ T cells, CD8+ T cells. Meanwhile, O-Ag-MBP induced the upregulation of Th1-related IFN-γ and downregulation of Th2-related IL-4, and the upregulation of IFN-γ was stimulated by MBP in a dose-dependent manner. MBP showed TLR4 agonist-like properties to activate Th1 cells as carrier protein of O-Ag-MBP. Thus, glycoconjugate vaccine E. coli O157:H7-specific O-Ag-MBP produced by bacterial protein N-linked glycosylation system was able to elicit both humoral and Th1-biased cellular responses.
authors.affiliation: School of Life Sciences and The State Key Laboratory of Microbial Technology, National Glycoengineering Research Center, Shandong University, Jinan, Shandong, China.
authors.forename: Zhongrui
authors.initials: Z
authors.lastname: Ma
authors.affiliation: School of Life Sciences and The State Key Laboratory of Microbial Technology, National Glycoengineering Research Center, Shandong University, Jinan, Shandong, China.
authors.forename: Huajie
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry and Molecular Biology, Binzhou Medical University, YanTai, Shandong, China.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Shang
authors.affiliation: Department of Immunology, Shandong University School of Medicine, Jinan, Shandong, China.
authors.forename: Faliang
authors.initials: F
authors.lastname: Zhu
authors.affiliation: College of Pharmacy and the State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, China.
authors.forename: Weiqing
authors.initials: W
authors.lastname: Han
authors.affiliation: School of Life Sciences and The State Key Laboratory of Microbial Technology, National Glycoengineering Research Center, Shandong University, Jinan, Shandong, China.
authors.forename: Xueer
authors.initials: X
authors.lastname: Zhao
authors.affiliation: School of Life Sciences and The State Key Laboratory of Microbial Technology, National Glycoengineering Research Center, Shandong University, Jinan, Shandong, China.
authors.forename: Donglei
authors.initials: D
authors.lastname: Han
authors.affiliation: School of Life Sciences and The State Key Laboratory of Microbial Technology, National Glycoengineering Research Center, Shandong University, Jinan, Shandong, China.
authors.forename: Peng George
authors.initials: PG
authors.lastname: Wang
authors.affiliation: School of Life Sciences and The State Key Laboratory of Microbial Technology, National Glycoengineering Research Center, Shandong University, Jinan, Shandong, China.
authors.forename: Min
authors.initials: M
authors.lastname: Chen
mesh_terms: D000818:Animals; D021461:Animals, Outbred Strains; D000907:Antibodies, Bacterial / Q000097:blood; D004927:Escherichia coli Infections / Q000517:prevention & control*; D019453:Escherichia coli O157 / Q000276:immunology; D022361:Escherichia coli Vaccines / Q000276:immunology*; D005260:Female; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D051379:Mice; D019081:O Antigens / Q000276:immunology*; D014611:Vaccination
chemical_list: D000907:Antibodies, Bacterial; D022361:Escherichia coli Vaccines; D019081:O Antigens