Modulation of gene-gun-mediated Th2 immunity to hepatitis B surface antigen by bacterial CpG motifs or IL-12.

Using different DNA vaccination techniques, we studied the IgG1/IgG2a antibody and MHC-I-restricted cytotoxic T lymphocyte (CTL) responses to the hepatitis B surface antigen (HBsAg) in mice. A single intramuscular injection of 100 microg HBsAg-encoding pCI/S plasmid DNA efficiently primed IgG2a antibody (IgG1/IgG2a ratio <0.3) and CTL responses to HBsAg (Th1 immunity). In contrast, a single intradermal injection of 1 microg of particle-coated pCI/S DNA with the gene-gun-primed IgG1 antibody responses to HBsAg (IgG1/IgG2a ratio >80) but there was no CTL response (Th2 immunity). Injection of immune-stimulating CpG-containing oligodeoxy-nucleotides (ODN) into the skin area used for gene-gun-mediated pCI/S DNA delivery shifted the polarization of the response towards Th1 immunity. A similar shift from Th2 to Th1 immunity was observed when the skin area used for gene-gun-mediated DNA transfer was conditioned by injection of recombinant IL-12. DNA vaccination can thus prime polarized immunity to HBsAg. The polarization of immunity is determined by the technique of plasmid DNA delivery as well as by conditions of the tissue into which DNA is inoculated. Th1 immunity to HBsAg (primed by injection of naked pCI/S DNA) dominated Th2 immunity (primed by gene-gun-mediated pCI/S DNA). In contrast, an established HBsAg-specific Th2 immunity was readily shifted towards Th1 immunity (including specific CTL priming) by an intramuscular boost injection of pCI/S DNA. These data contribute to the rational design of DNA vaccination strategies to efficiently prime anti-viral Th1 immune effector specificities using the gene gun. Copyright 2001 S. Karger AG, Basel