Evaluation of protective efficacy and immune mechanisms of using a non-structural protein NS1 in DNA vaccine against dengue 2 virus in mice

Vaccine. 2003 Sep 8;21(25-26):3919-29. doi: 10.1016/s0264-410x(03)00310-4.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Antibody Formation / immunology
  • Cell Division / drug effects
  • Cell Line
  • Cytokines / biosynthesis
  • Cytokines / genetics
  • DNA, Bacterial / genetics
  • DNA, Bacterial / immunology
  • Dengue / immunology
  • Dengue / prevention & control*
  • Dengue Virus / immunology*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Immunity, Cellular / immunology
  • Immunoblotting
  • Indicators and Reagents
  • Interleukin-12 / physiology
  • Lymphocyte Count
  • Male
  • Mice
  • Mice, Inbred C3H
  • Plasmids / genetics
  • Plasmids / immunology
  • Precipitin Tests
  • Reverse Transcriptase Polymerase Chain Reaction
  • Survival Analysis
  • T-Lymphocytes / immunology
  • Th1 Cells / immunology
  • Vaccines, DNA / immunology*
  • Viral Nonstructural Proteins / immunology*
  • Viral Vaccines / immunology*

Substances

  • Cytokines
  • DNA, Bacterial
  • Indicators and Reagents
  • NS1 protein, Dengue virus type 2
  • Vaccines, DNA
  • Viral Nonstructural Proteins
  • Viral Vaccines
  • Interleukin-12