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 antib ody and MHC-1-restricted cytotoxic T lymphocyte (CTL) responses to the hepa titis B surface antigen (HBsAg) in mice. A single intramuscular injection o f 100 mug HBsAg-encoding pCI/S plasmid DNA efficiently primed IgG2a antibod y (IgG1/IgG2a ratio <0.3) and CTL responses to HBsAg (Th1 immunity). In con trast, a single intradermal injection of 1 mug of particle-coated pCl/S DNA with the gene-gun-primed IgG1 antibody responses to HBsAg (IgG1/IgG2a rati o > 80) but there was no CTL response (Th2 immunity). Injection of immune-s timulating CpG-containing oligodeoxy-nucleotides (ODN) into the skin area u sed for gene-gun-mediated pCl/S DNA delivery shifted the polarization of th e response towards Th1 immunity. A similar shift from Th2 to Th1 immunity w as observed when the skin area used for gene-gun-mediated DNA transfer was conditioned by injection of recombinant IL-12. DNA vaccination can thus pri me polarized immunity to HBsAg. The polarization of immunity is determined by the technique of plasmid DNA delivery as well as by conditions of the ti ssue into which DNA is inoculated. Th1 immunity to HBsAg (primed by injecti on 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 rea dily shifted towards Th1 immunity (including specific CTL priming) by an in tramuscular boost injection of pCI/S DNA. These data contribute to the rati onal design of DNA vaccination strategies to efficiently prime anti-viral T h1 immune effector specificities using the gene gun. Copyright (C) 2001 S. Karger AG, Basel.