Evaluation of protective efficacy and immune mechanisms of using a non-structural protein NS1 in DNA vaccine against dengue 2 virus in mice.
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.
Wu
Shu-Fen
SF
Department of Microbiology and Immunology, National Defense Medical Center, P.O. Box 90048-505, Neihu, Taipei, Taiwan, ROC.
Liao
Ching-Len
CL
Lin
Yi-Ling
YL
Yeh
Chia-Tsui
CT
Chen
Li-Kuang
LK
Huang
Yung-Feng
YF
Chou
Hsin-Ying
HY
Huang
Jau-Ling
JL
Shaio
Men-Fang
MF
Sytwu
Huey-Kang
HK
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*
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