title: Induction of robust immunity by the emulsification of recombinant lipidated dengue-1 envelope protein domain III.
abstract: Many attempts have focused on the use of either immunomodulators or antigen delivery systems to obtain an efficacious vaccine. Here, we report a novel approach that combined an immunomodulator and delivery system to enhance antigen association and induce robust immunity. We expressed a recombinant lipidated dengue-1 envelope protein domain III (LD1ED III) and its non-lipidated form, D1ED III, in an Escherichia coli system. The LD1ED III contains a bacterial lipid moiety, which is a potent immunomodulator. We demonstrated that LD1ED III possesses an inherent immunostimulation ability that can activate RAW 264.7 macrophage cells by up-regulating their expression of CD40, CD80, CD83, CD86 and MHC II, whereas D1ED III could not induce the up-regulation of these molecules. Moreover, combining LD1ED III with a multiphase emulsion system (called PELC) increased the antigen association more than either combining D1ED III with PELC or the antigen alone. Enhanced antigen association has been shown to correlate with stronger T cell responses, greater antibody avidity and improved neutralizing capacity. Our results demonstrate that combining recombinant lipoproteins with PELC improved both the intensity and the quality of the immune response. This approach is a promising strategy for the development of subunit vaccines that induce robust immunity.
authors.affiliation: National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli, Taiwan, ROC.
authors.forename: Chen-Yi
authors.initials: CY
authors.lastname: Chiang
authors.forename: Ming-Hsi
authors.initials: MH
authors.lastname: Huang
authors.forename: Chien-Hsiung
authors.initials: CH
authors.lastname: Pan
authors.forename: Chun-Hsiang
authors.initials: CH
authors.lastname: Hsieh
authors.forename: Mei-Yu
authors.initials: MY
authors.lastname: Chen
authors.forename: Hsueh-Hung
authors.initials: HH
authors.lastname: Liu
authors.forename: Jy-Ping
authors.initials: JP
authors.lastname: Tsai
authors.forename: Shih-Jen
authors.initials: SJ
authors.lastname: Liu
authors.forename: Pele
authors.initials: P
authors.lastname: Chong
authors.forename: Chih-Hsiang
authors.initials: CH
authors.lastname: Leng
authors.forename: Hsin-Wei
authors.initials: HW
authors.lastname: Chen
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral / Q000097:blood; D000915:Antibody Affinity; D015703:Antigens, CD / Q000096:biosynthesis; D002460:Cell Line; D053059:Dengue Vaccines / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology*; D003716:Dengue Virus / Q000235:genetics / Q000276:immunology*; D004655:Emulsions / Q000008:administration & dosage*; D004926:Escherichia coli / Q000235:genetics; D015870:Gene Expression; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D008055:Lipids / Q000008:administration & dosage*; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D013601:T-Lymphocytes / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D015703:Antigens, CD; D053059:Dengue Vaccines; D004655:Emulsions; D000949:Histocompatibility Antigens Class II; D008055:Lipids; D014614:Vaccines, Synthetic; D014759:Viral Envelope Proteins
keywords: Dengue; Immune response; Immunostimulation; Lipoprotein