title: Induction of multiple cytotoxic T lymphocyte responses in mice by a multiepitope DNA vaccine against dengue virus serotype 1.
abstract: Dengue virus (DENV) is still a major threat to human health in most tropical and subtropical countries and regions. In the present study, a multi-epitope DNA vaccine that encodes 15 immunogenic and conserved HLA-A*0201-, HLA-A*1101-, HLA-A*2402-restricted CTL epitopes from DENV serotype 1 (DENV-1) was constructed based on the eukaryotic expressing plasmid pcDNATM3.1/myc-His(-) A. Immunization of HLA-A*0201, HLA-A*1101 and HLA-A*2402 transgenic mice with the recombinant plasmid pcDNATM3.1/myc-His(-) A-DENV-1-Meg resulted in significantly greater IFN-γ-secreting T-cell responses against most (14/15) CTL epitopes than occurred in mice immunized with the empty plasmid pcDNATM3.1/myc-His(-) A. Additionally, the epitope-specific T cells directed to some epitopes secreted not only IFN-γ but also IL-6 and/or TNF-α. Finally, the induced epitope-specific T cells also efficiently lysed epitope-pulsed splenocytes and DENV-1-infected splenic monocytes. The present study confirms the immunogenicity of multi-epitope DENV vaccine, suggesting that it may contribute to the development of a universal DENV vaccine.
authors.affiliation: Department of Clinical Laboratory, Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Xueyuan West Road, Wenzhou 325000.
authors.forename: Xin Yu
authors.initials: XY
authors.lastname: Chen
authors.affiliation: Department of Liver, The Second Hospital of Ningbo, Ningbo 315010, China.
authors.forename: De Zhou
authors.initials: Z
authors.lastname: Li
authors.affiliation: Institute of Arboviruses, School of Basic Medical Sciences, Wenzhou Medical University, Chashan, Wenzhou 32500.
authors.forename: Xiao Zhi
authors.initials: XZ
authors.lastname: Zhong
authors.affiliation: Institute of Arboviruses, School of Basic Medical Sciences, Wenzhou Medical University, Chashan, Wenzhou 32500.
authors.forename: Bokun
authors.initials: B
authors.lastname: Chen
authors.affiliation: Department of Clinical Laboratory, Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Xueyuan West Road, Wenzhou 325000.
authors.forename: Zhi Liang
authors.initials: ZL
authors.lastname: Duan
authors.affiliation: Institute of Arboviruses, School of Basic Medical Sciences, Wenzhou Medical University, Chashan, Wenzhou 32500.
authors.forename: Jin Sheng
authors.initials: JS
authors.lastname: Wen
mesh_terms: D000818:Animals; D003601:Cytotoxicity Tests, Immunologic; D003716:Dengue Virus / Q000235:genetics / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D005260:Female; D015234:HLA-A Antigens / Q000235:genetics; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008822:Mice, Transgenic; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
chemical_list: D018984:Epitopes, T-Lymphocyte; D015234:HLA-A Antigens; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D019444:Vaccines, DNA; D014614:Vaccines, Synthetic; C577686:interleukin-6, mouse; D007371:Interferon-gamma
keywords: DNA vaccine; cytotoxic T lymphocyte; dengue virus; epitope