CYTOKINE AND HEPATITIS-B VIRUS-DNA CO-IMMUNIZATIONS ENHANCE CELLULAR AND HUMORAL IMMUNE-RESPONSES TO THE MIDDLE BUT NOT TO THE LARGE HEPATITIS-B VIRUS SURFACE-ANTIGEN IN MICE

Genetic immunization is a potentially useful strategy to prevent or tr eat hepatitis B virus (I-IBV) infection, We have previously shown that HBV envelope proteins are highly immunogenic using this technique. Th e large envelope protein (LHBs), however, induced significantly weaker humoral and cellular immune responses when compared with the middle e nvelope protein (MHBs), We studied the effect of co-immunizations with cytokine: DNA expression constructs encoding for interleukin (IL)-2 a nd (GM-CSF) on the immunogenicity of LHBs at the B-and T-cell level, G o-immunizations of mice with plasmids encoding for MHBs and IL-2 or GM -CSF increased anti-HBs responses, helper T-cell proliferative activit y, and cytotoxic T lymphocyte (CTL) killing, In contrast, co-immunizat ions of plasmids encoding for LHBs and IL-2 or GM-CSF had no effect on humoral and cellular immune responses, LHBs did not inhibit the produ ction or secretion of IL-2 and GM-CSE In addition, IL-2, tumor necrosi s factor alfa (TNF-alpha), and interferon gamma (IFN-gamma) had no sup pressive effect on HBV envelope protein expression in vitro, Based on these data, MMBs, but not LHBs, genetic immunization can be augmented by IL-2 or GM-CSF cytokines.