title: Immunisation With Immunodominant Linear B Cell Epitopes Vaccine of Manganese Transport Protein C Confers Protection against Staphylococcus aureus Infection.
abstract: Vaccination strategies for Staphylococcus aureus, particularly methicillin-resistant S. aureus (MRSA) infections have attracted much research attention. Recent efforts have been made to select manganese transport protein C, or manganese binding surface lipoprotein C (MntC), which is a metal ion associated with pathogen nutrition uptake, as potential candidates for an S. aureus vaccine. Although protective humoral immune responses to MntC are well-characterised, much less is known about detailed MntC-specific B cell epitope mapping and particularly epitope vaccines, which are less-time consuming and more convenient. In this study, we generated a recombinant protein rMntC which induced strong antibody response when used for immunisation with CFA/IFA adjuvant. On the basis of the results, linear B cell epitopes within MntC were finely mapped using a series of overlapping synthetic peptides. Further studies indicate that MntC113-136, MntC209-232, and MntC263-286 might be the original linear B-cell immune dominant epitope of MntC, furthermore, three-dimensional (3-d) crystal structure results indicate that the three immunodominant epitopes were displayed on the surface of the MntC antigen. On the basis of immunodominant MntC113-136, MntC209-232, and MntC263-286 peptides, the epitope vaccine for S. aureus induces a high antibody level which is biased to TH2 and provides effective immune protection and strong opsonophagocytic killing activity in vitro against MRSA infection. In summary, the study provides strong proof of the optimisation of MRSA B cell epitope vaccine designs and their use, which was based on the MntC antigen in the development of an MRSA vaccine.
authors.affiliation: National Engineering Research Centre for Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing 400038, PR China.
authors.forename: Hui-Jie
authors.initials: HJ
authors.lastname: Yang
authors.affiliation: National Engineering Research Centre for Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing 400038, PR China.
authors.forename: Jin-Yong
authors.initials: JY
authors.lastname: Zhang
authors.affiliation: National Engineering Research Centre for Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing 400038, PR China.
authors.forename: Chao
authors.initials: C
authors.lastname: Wei
authors.affiliation: National Engineering Research Centre for Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing 400038, PR China.
authors.forename: Liu-Yang
authors.initials: LY
authors.lastname: Yang
authors.affiliation: National Engineering Research Centre for Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing 400038, PR China.
authors.forename: Qian-Fei
authors.initials: QF
authors.lastname: Zuo
authors.affiliation: National Engineering Research Centre for Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing 400038, PR China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhuang
authors.affiliation: School of Basic Medical Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, PR China.
authors.forename: You-Jun
authors.initials: YJ
authors.lastname: Feng
authors.affiliation: Department of Biochemistry, University of Illinois, Urbana, IL, 61801, United States of America.
authors.forename: Swaminath
authors.initials: S
authors.lastname: Srinivas
authors.affiliation: National Engineering Research Centre for Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing 400038, PR China.
authors.forename: Hao
authors.initials: H
authors.lastname: Zeng
authors.affiliation: National Engineering Research Centre for Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing 400038, PR China.
authors.forename: Quan-Ming
authors.initials: QM
authors.lastname: Zou
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology*; D027682:Cation Transport Proteins / Q000235:genetics / Q000276:immunology*; D018604:Epitope Mapping; D018985:Epitopes, B-Lymphocyte / Q000276:immunology*; D005260:Female; D018922:HL-60 Cells; D006433:Hemocyanins / Q000276:immunology; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology*; D008345:Manganese; D055624:Methicillin-Resistant Staphylococcus aureus / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010587:Phagocytosis; D013203:Staphylococcal Infections / Q000276:immunology / Q000517:prevention & control*; D013209:Staphylococcal Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D018074:Vaccines, Conjugate / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D027682:Cation Transport Proteins; D018985:Epitopes, B-Lymphocyte; D016056:Immunodominant Epitopes; D013209:Staphylococcal Vaccines; D018074:Vaccines, Conjugate; D014614:Vaccines, Synthetic; D008345:Manganese; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin