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 (HB5Ag) was cloned into expression plasmid pCI under either a viral (CMV) promoter;enhancer sequence control (plasmid pCI/S), or a human desmin promoter/enhancer sequence control (plasmid pDes/S). Cells of different species and tissue origin transiently transfected in vitro with pCI/S or pDes/S plasmid DNA expressed readily detectable amounts of HBsAg, either intracellularly (precipitated from cell lysates), or as secreted products (detectable in ELISA). When these plasmids were used in DNA vaccination, both efficiently primed humoral and/or cellular immune responses to HBsAg after a single injection in Balb/c mice. Intramuscular injection of a high dose of DNA (100 rig/mouse) of both plasmids primed MHC-I-restricted cytotoxic T lymphocyte (CTL) responses and Thi serum antibody responses (IgGlIgG2a ratio O.4C0.7) of comparable magnitude in all vaccinated mice. Intradermal injection of low doses of (particle-coated) DNA (1 microgm/mouse) of both plasmids with the gene gun primed Th2 serum antibody responses (IgGl/IgG2a ratio > 100) but no CTL responses. The data indicate that antigens can be efficiently expressed under viral or eukaryotic promoter/enhancer control for immunogenic in vivo presentation, but that the technique, dose and/or route of DNA injection have a decisive role in determining the type of immune response elicited.
Kwissa
M
M
Institute for Medical Microbiology, University of Ulm, Helmholtzstr. 8/1, D-89081, Ulm, Germany.
von Kampen
v K
vK
Zurbriggen
R
R
Glück
R
R
Reimann
J
J
Schirmbeck
R
R
D000818:Animals; D002460:Cell Line; D003893:Desmin / Q000235:genetics; D004742:Enhancer Elements, Genetic; D005260:Female; D006510:Hepatitis B Antibodies / Q000096:biosynthesis; D006514:Hepatitis B Surface Antigens / Q000235:genetics*; D017325:Hepatitis B Vaccines / Q000008:administration & dosage* / Q000235:genetics; D006801:Humans; D007271:Injections, Intradermal; D007273:Injections, Intramuscular; D051379:Mice; D008807:Mice, Inbred BALB C; D010957:Plasmids / Q000235:genetics; D011401:Promoter Regions, Genetic; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000235:genetics
D003893:Desmin; D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D019444:Vaccines, DNA