ISS (ImmunoStimulatory Sequences) and Iscomatrix boost vaccine-generated HBV-specific immunity in mice (B202)

We have investigated the adjuvant activity of both CpG motif-containing ImmunoStimulatory Sequences (ISS) and the saponin/phospholipid-based Iscomatrix (IMX) on HBV-specific humoral and cell-mediated immunity in C57BL/6 mice. Mice were immunized at weeks 0 and 2 with several formulations that incorporated HBV surface antigen (HBsAg), HBV core antigen (HBcAg), ISS, and IMX. ISS was added to antigen in soluble form or conjugated with HBsAg or HBcAg. Bleeds were performed 2 weeks post 1st immunization (2wp1) and 2wp2 and sera analyzed for anti-HBV IgG1 and IgG2a levels. Mice were also splenectomized at 2wp2 and HBV-specific cell-mediated immunity was examined. HBsAg + HBcAg + 1018 ISS + IMX resulted in high levels of HBsAg-specific and HBcAg-specific IFN-g induction that exceeded that induced by either adjuvant alone. Conjugates of HBV surface or core protein to ISS ODNs also provided for higher levels of antigen-specific IFN-g production and CTL activation. These results indicate that HBV therapeutic formulations that incorporate ISS and/or IMX may stimulate for enhanced levels of anti-HBsAg antibody and augmented anti-HBcAg CMI (cell-mediated immunity) and are promising candidates to test in human clinical trials.