title: Recombinant lipidated dengue-3 envelope protein domain III stimulates broad immune responses in mice.
abstract: The linkage of an immunogen with a toll-like receptor ligand has great potential to induce highly potent immune responses with the initial features of antigen-presenting cell activation. In the current study, we expressed recombinant dengue-3 envelope protein domain III (D3ED III) in lipidated form using an Escherichia coli-based system. The recombinant lipidated dengue-3 envelope protein domain III (LD3ED III) augments the expression levels of IL-12 family cytokines. LD3ED III-immunized mice enhance wide ranges of T cell responses as indicated by IFN-γ, IL-17, IL-21 production. Additionally, LD3ED III-immunized mice increase the frequencies of anti-D3ED III antibody producing cells. The boosted antibody titers cover various IgG isotypes, including IgG1, IgG2a, IgG2b, and IgG3. Importantly, LD3ED III-immunized mice induce neutralizing antibody capacity associated with a reduction of viremia levels after challenges. In contrast, mice that are immunized with D3ED III formulated with aluminum phosphate (D3ED III/Alum) only enhance Th2 responses and boost IgG1 antibody titers. Neither neutralizing antibody responses nor the inhibition of viremia levels after challenge is observed in mice that are immunized with D3ED III/Alum. These results suggest that LD3ED III can induce broad profiles of cellular and humoral immune responses.
authors.affiliation: National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, Miaoli, Taiwan.
authors.forename: Chen-Yi
authors.initials: CY
authors.lastname: Chiang
authors.affiliation: National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, Miaoli, Taiwan; Graduate Institute of Immunology, China Medical University, Taichung, Taiwan.
authors.forename: Shih-Jen
authors.initials: SJ
authors.lastname: Liu
authors.affiliation: National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, Miaoli, Taiwan.
authors.forename: Chun-Hsiang
authors.initials: CH
authors.lastname: Hsieh
authors.affiliation: National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, Miaoli, Taiwan.
authors.forename: Mei-Yu
authors.initials: MY
authors.lastname: Chen
authors.affiliation: National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, Miaoli, Taiwan.
authors.forename: Jy-Ping
authors.initials: JP
authors.lastname: Tsai
authors.affiliation: National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, Miaoli, Taiwan.
authors.forename: Hsueh-Hung
authors.initials: HH
authors.lastname: Liu
authors.affiliation: National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, Miaoli, Taiwan.
authors.forename: I-Hua
authors.initials: IH
authors.lastname: Chen
authors.affiliation: National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, Miaoli, Taiwan; Graduate Institute of Immunology, China Medical University, Taichung, Taiwan.
authors.forename: Pele
authors.initials: P
authors.lastname: Chong
authors.affiliation: National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, Miaoli, Taiwan; Graduate Institute of Immunology, China Medical University, Taichung, Taiwan. Electronic address: leoleng@nhri.org.tw.
authors.forename: Chih-Hsiang
authors.initials: CH
authors.lastname: Leng
authors.affiliation: National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, Miaoli, Taiwan; Graduate Institute of Immunology, China Medical University, Taichung, Taiwan. Electronic address: chenhw@nhri.org.tw.
authors.forename: Hsin-Wei
authors.initials: HW
authors.lastname: Chen
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D003715:Dengue / Q000517:prevention & control*; D053059:Dengue Vaccines / Q000276:immunology*; D003716:Dengue Virus; D005260:Female; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D007074:Immunoglobulin G / Q000097:blood; D008055:Lipids / Q000737:chemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014759:Viral Envelope Proteins / Q000276:immunology*; D014766:Viremia / Q000517:prevention & control
chemical_list: D000276:Adjuvants, Immunologic; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D016207:Cytokines; D053059:Dengue Vaccines; C084188:E protein, Dengue virus type 3; D007074:Immunoglobulin G; D008055:Lipids; D011994:Recombinant Proteins; D014759:Viral Envelope Proteins
keywords: Dengue virus; Envelope protein domain III; Lipoprotein; Vaccine