Efficient vaccination by intradermal or intramuscular inoculation of plasmid DNA expressing hepatitis B surface antigen under desmin promoter/enhancer control

The small surface antigen of the hepatitis B virus (HBsAg) was cloned into expression plasmid pCI under either a viral (CMV) promoter/enhancer sequenc e control (plasmid pCI/S), or a human desmin promoter/enhancer sequence con trol (plasmid pDes/S). Cells of different species and tissue origin transie ntly transfected in vitro with pCI/S or pDes/S plasmid DNA expressed readil y detectable amounts of HBsAg, either intracellularly (precipitated from ce ll lysates), or as secreted products (detectable in ELISA). When these plas mids were used in DNA vaccination, both efficiently primed humoral and/or c ellular immune responses to HBsAg after a single injection in Balb/c mice. Intramuscular injection of a high dose of DNA (100 mu g/mouse) of both plas mids primed MHC-I-restricted cytotoxic T lymphocyte (CTL) responses and Thl serum antibody responses (IgG1/IgG2a ratio 0.4-0.7) of comparable magnitud e in all vaccinated mice. Intradermal injection of low doses of (particle-c oated) DNA (1 mu g/mouse) of both plasmids with the gene gun primed Th2 ser um antibody responses (IgG1/IgG2a ratio > 100) but no CTL responses. The da ta indicate that antigens can be efficiently expressed under viral or eukar yotic promoter/enhancer control for immunogenic in vivo presentation, but t hat the technique, dose and/or route of DNA injection have a decisive role in determining the type of immune response elicited. (C) 2000 Elsevier Scie nce Ltd. All rights reserved.