Induction of Tc1 response and enhanced cytotoxic T lymphocyte activity in mice by dendritic cells transduced with adenovirus expressing HBsAg

Clin Immunol. 2006 Jun;119(3):280-90. doi: 10.1016/j.clim.2006.01.015. Epub 2006 Mar 10.

Abstract

We evaluated the potential of dendritic cells (DCs) engineered to express antigen of hepatitis B virus (HBV) in priming Th/Tc and HBV-specific CTL responses in mice. Recombinant adenovirus expressing hepatitis B surface antigen (HBsAg) (Ad-S) was constructed, and bone marrow-derived DCs were transduced with Ad-S or pulsed with HBsAg protein. Mice were injected with either Ad-S-transduced DCs or HBsAg-pulsed DCs or plasmid DNA encoding HBsAg twice at 3-week intervals. We showed that adenovirus infection had no further effect on the phenotype, the ability to induce IFN-gamma-producing Th1/Tc1 response or the T cell stimulatory capacity of already mature DCs in vitro. We also showed that immunization with Ad-S-transduced DCs effectively induced Tc1 cells and HBsAg-specific CTLs in vivo and down-regulated the circulating HBsAg and HBV DNA in HBV transgenic mice. Furthermore, these efficacies were stronger than that of HBsAg-pulsed DCs and plasmid DNA. Thus, DCs transduced with recombinant adenovirus may be a promising candidate for an effective CTL-based therapeutic vaccine against HBV.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics*
  • Animals
  • DNA, Viral / blood
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Female
  • Hepatitis B / prevention & control
  • Hepatitis B Surface Antigens / blood
  • Hepatitis B Surface Antigens / genetics*
  • Hepatitis B Surface Antigens / immunology*
  • Immunization
  • Interferon-gamma / immunology
  • Interleukin-4 / immunology
  • Lymphocyte Culture Test, Mixed
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Spleen / cytology
  • T-Lymphocytes, Cytotoxic / immunology*
  • Transduction, Genetic
  • Vaccines, DNA

Substances

  • DNA, Viral
  • Hepatitis B Surface Antigens
  • Vaccines, DNA
  • Interleukin-4
  • Interferon-gamma