title: Evaluation of protective efficacy and immune mechanisms of using a non-structural protein NS1 in DNA vaccine against dengue 2 virus in mice.
abstract: To evaluate the potential of DNA vaccine against dengue (DEN) infection, we characterize the protective efficacy and immune responses of mice intramuscularly injected with plasmid encoding DEN-2 non-structural protein 1 (NS1). Intravenously challenged by lethal DEN-2, mice vaccinated with NS1-DNA exhibited a delay onset of paralysis, a marked decrease of morbidity, and a significant enhancement of survival. In addition to a moderate increase of NS1-specific antibody titer from immunized mice measured by ELISA, a strong priming effect on anti-NS1 response was also noticed in plasmid NS1-vaccinated mice by radioimmunoprecipitation (RIP) or immunoblot analysis. Interestingly, newborn mice from NS1-DNA-immunized dam showed stronger resistance to viral challenge, as compared to those from vector DNA or PBS-immunized dams, indicating the protective role of NS1-specific antibody. In contrast to humoral immune response, DNA immunization can elicit strong cellular immune responses, including NS1-specific T cell proliferation and cytolytic activity. The NS1-DNA-induced protection can be further augmented by co-injection of plasmid encoding interleukin 12 (IL-12), suggesting an effector role of Th1 immunity against DEN infection. In summary, our results suggest the potential of NS1-DNA vaccine against DEN infection, and indicate both NS1-specific humoral and cellular immune responses contribute to the protection.
authors.affiliation: Department of Microbiology and Immunology, National Defense Medical Center, P.O. Box 90048-505, Neihu, Taipei, Taiwan, ROC.
authors.forename: Shu-Fen
authors.initials: SF
authors.lastname: Wu
authors.forename: Ching-Len
authors.initials: CL
authors.lastname: Liao
authors.forename: Yi-Ling
authors.initials: YL
authors.lastname: Lin
authors.forename: Chia-Tsui
authors.initials: CT
authors.lastname: Yeh
authors.forename: Li-Kuang
authors.initials: LK
authors.lastname: Chen
authors.forename: Yung-Feng
authors.initials: YF
authors.lastname: Huang
authors.forename: Hsin-Ying
authors.initials: HY
authors.lastname: Chou
authors.forename: Jau-Ling
authors.initials: JL
authors.lastname: Huang
authors.forename: Men-Fang
authors.initials: MF
authors.lastname: Shaio
authors.forename: Huey-Kang
authors.initials: HK
authors.lastname: Sytwu
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000917:Antibody Formation / Q000276:immunology; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D004269:DNA, Bacterial / Q000235:genetics / Q000276:immunology; D003715:Dengue / Q000276:immunology / Q000517:prevention & control*; D003716:Dengue Virus / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007111:Immunity, Cellular / Q000276:immunology; D015151:Immunoblotting; D007202:Indicators and Reagents; D018664:Interleukin-12 / Q000502:physiology; D018655:Lymphocyte Count; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D010957:Plasmids / Q000235:genetics / Q000276:immunology; D011233:Precipitin Tests; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D019444:Vaccines, DNA / Q000276:immunology*; D017361:Viral Nonstructural Proteins / Q000276:immunology*; D014765:Viral Vaccines / Q000276:immunology*
chemical_list: D016207:Cytokines; D004269:DNA, Bacterial; D007202:Indicators and Reagents; C079340:NS1 protein, Dengue virus type 2; D019444:Vaccines, DNA; D017361:Viral Nonstructural Proteins; D014765:Viral Vaccines; D018664:Interleukin-12