CpG oligodeoxynucleotides with hepatitis B surface antigen (HBsAg) for vaccination in HBsAg-Transgenic mice

DNA motifs containing unmethylated CpG dinucleotides within the context of certain flanking sequences enhance both innate and antigen-specific immune responses, due in part to tile. enhanced production of Th1-type cytokines. Here we explored the ability of CpG containing oligodeoxynucleotides combin ed with recombinant hepatitis B surface antigen (HBsAg) to induce Th1 respo nses in mice that are transgenic for this antigen and that represent a mode l for asymptomatic hepatitis B virus chronic carriers. This was compared to hepatitis B virus-specific DNA-mediated immunization, which we have previo usly shown to induce the clearance of the transgene expression product and the down-regulation of hepatitis B virus mRNA in this transgenic mouse line age. In control nontransgenic C57BL/6 mice, three immunizations with HBsAg and CpG triggered the production of anti-HBs antibodies and of HBs-specific T cells that secrete gamma interferon but do not display any HBsAg-specifi c cytotoxic activity. In the HBsAg-transgenic mice, immunization with HBsAg and CPG oligodeoxynucleotides, but not with CpG alone, induced the clearan ce of HBsAg circulating in the sera, with a concomitant appearance of speci fic antibodies, and was able to regulate the hepatitis II virus mRNA consti tutively expressed in the liver. Finally, adoptive transfer experiments wit h CD8(+) T cells primed in C57BL/6 mice with HBsAg and CpG oligodeoxynucleo tide based immunization show that these cells were able to partially contro l transgene expression in the liver and to clear the HBsAg from the sera of recipient transgenic mice without an antibody requirement. CpG oligodeoxyn ucleotides motifs combined with HBsAg could therefore represent a potential therapeutic approach with which to treat chronically infected patients.