title: Protective efficacy of the chimeric Staphylococcus aureus vaccine candidate IC in sepsis and pneumonia models.
abstract: Staphylococcus aureus causes serious sepsis and necrotic pneumonia worldwide. Due to the spread of multidrug-resistant strains, developing an effective vaccine is the most promising method for combating S. aureus infection. In this study, based on the immune-dominant areas of the iron surface determinant B (IsdB) and clumping factor A (ClfA), we designed the novel chimeric vaccine IsdB151-277ClfA33-213 (IC). IC formulated with the AlPO4 adjuvant induced higher protection in an S. aureus sepsis model compared with the single components alone and showed broad immune protection against several clinical S. aureus isolates. Immunisation with IC induced strong antibody responses. The protective effect of antibodies was demonstrated through the opsonophagocytic assay (OPA) and passive immunisation experiment. Moreover, this new chimeric vaccine induced Th1/Th17-skewed cellular immune responses based on cytokine profiles and CD4(+) T cell stimulation tests. Neutralisation of IL-17A alone (but not IFN-γ) resulted in a significant decrease in vaccine immune protection. Finally, we found that IC showed protective efficacy in a pneumonia model. Taken together, these data provide evidence that IC is a potentially promising vaccine candidate for combating S. aureus sepsis and pneumonia.
authors: National Engineering Research Center of Immunological Products &Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing 400038, P.R. China.
authors: Liuyang
authors: L
authors: Yang
authors: National Engineering Research Center of Immunological Products &Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing 400038, P.R. China.
authors: Changzhi
authors: C
authors: Cai
authors: Department of Biological and Chemical Engineering, Chongqing University of Education, Chongqing 400067, P.R. China.
authors: Qiang
authors: Q
authors: Feng
authors: National Engineering Research Center of Immunological Products &Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing 400038, P.R. China.
authors: Yun
authors: Y
authors: Shi
authors: National Engineering Research Center of Immunological Products &Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing 400038, P.R. China.
authors: Qianfei
authors: Q
authors: Zuo
authors: National Engineering Research Center of Immunological Products &Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing 400038, P.R. China.
authors: Huijie
authors: H
authors: Yang
authors: National Engineering Research Center of Immunological Products &Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing 400038, P.R. China.
authors: Haiming
authors: H
authors: Jing
authors: National Engineering Research Center of Immunological Products &Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing 400038, P.R. China.
authors: Chao
authors: C
authors: Wei
authors: National Engineering Research Center of Immunological Products &Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing 400038, P.R. China.
authors: Yuan
authors: Y
authors: Zhuang
authors: National Engineering Research Center of Immunological Products &Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing 400038, P.R. China.
authors: Quanming
authors: Q
authors: Zou
authors: National Engineering Research Center of Immunological Products &Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing 400038, P.R. China.
authors: Hao
authors: H
authors: Zeng
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D027682:Cation Transport Proteins / Q000235:genetics / Q000276:immunology; D003001:Cloning, Molecular; D003030:Coagulase / Q000235:genetics / Q000276:immunology; D004195:Disease Models, Animal; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D007114:Immunization; D020381:Interleukin-17 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011014:Pneumonia / Q000276:immunology / Q000382:microbiology / Q000401:mortality / Q000517:prevention & control*; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage* / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D018805:Sepsis / Q000276:immunology / Q000382:microbiology / Q000401:mortality / Q000517:prevention & control*; D013203:Staphylococcal Infections / Q000276:immunology / Q000382:microbiology / Q000401:mortality / Q000517:prevention & control*; D013209:Staphylococcal Vaccines / Q000008:administration & dosage* / Q000096:biosynthesis / Q000235:genetics; D013211:Staphylococcus aureus / Q000187:drug effects / Q000254:growth & development / Q000472:pathogenicity; D016019:Survival Analysis
chemical_list: D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D027682:Cation Transport Proteins; C515944:ClfA protein, Staphylococcus aureus; D003030:Coagulase; D020381:Interleukin-17; C510010:IsdB protein, Staphylococcus aureus; D011993:Recombinant Fusion Proteins; D013209:Staphylococcal Vaccines