title: Immunization with a ZmpB-based protein vaccine could protect against pneumococcal diseases in mice.
abstract: Zinc metalloprotease B (ZmpB) is present in all isolated pneumococcal strains and contributes to the pathogenesis of pneumococcal infection. In this study, recombinant ZmpB was cloned and expressed in Escherichia coli. The expression of ZmpB by different pneumococcal strains was detectable by Western blotting with antisera raised to recombinant ZmpB. Flow cytometry analysis demonstrated that anti-ZmpB polyclonal antibodies could bind to the cell surface of the pneumococcal strains analyzed. Both recombinant ZmpB protein and anti-ZmpB polyclonal antibodies significantly inhibited the adhesion of Streptococcus pneumoniae D39 to A549 cells. In mouse models, mucosal immunization with recombinant ZmpB could significantly reduce pneumococcal lung colonization caused by S. pneumoniae serotypes 19F and 14 and significantly increase mice survival times following invasive pneumococcal challenge with different pneumococcal strains, including serotypes 2, 3, 6B, and 14. Furthermore, intraperitoneal immunization with recombinant ZmpB in combination with the recombinant pneumolysin mutant (DeltaA146 Ply) and heat shock protein 40 (DnaJ) could enhance the protection against pneumococcal infection compared to protection provided by single-protein antigens. Passive immunization with hyperimmune antisera against these three antigens also demonstrated that the combination of three hyperimmune antisera could provide better protection than single antisera. Taken together, our results suggest that ZmpB is a good candidate pneumococcal vaccine antigen.
authors.affiliation: Department of Laboratory Medicine, Chongqing Medical University, Chongqing, People's Republic of China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Gong
authors.forename: Wenchun
authors.initials: W
authors.lastname: Xu
authors.forename: Yali
authors.initials: Y
authors.lastname: Cui
authors.forename: Xuemei
authors.initials: X
authors.lastname: Zhang
authors.forename: Run
authors.initials: R
authors.lastname: Yao
authors.forename: Dairong
authors.initials: D
authors.lastname: Li
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.forename: Yujuan
authors.initials: Y
authors.lastname: He
authors.forename: Ju
authors.initials: J
authors.lastname: Cao
authors.forename: Yibing
authors.initials: Y
authors.lastname: Yin
mesh_terms: D000276:Adjuvants, Immunologic; D058956:Administration, Mucosal; D000818:Animals; D001426:Bacterial Proteins / Q000008:administration & dosage / Q000276:immunology*; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000276:immunology*; D008666:Metalloendopeptidases / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011008:Pneumococcal Infections / Q000517:prevention & control*; D011994:Recombinant Proteins; D013301:Streptolysins / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D001426:Bacterial Proteins; D001428:Bacterial Vaccines; D011994:Recombinant Proteins; D013301:Streptolysins; C032290:plY protein, Streptococcus pneumoniae; C412019:ZmpB enzyme; D008666:Metalloendopeptidases