Woodchuck hepatitis virus (WHV) and hepatitis B virus (HBV) are closely similar with respect to genomic organization, host
antiviral responses, and pathobiology of the
infection. T-cell immunity against viral nucleocapsid (
HBcAg or WHcAg) has been shown to play a critical role in viral clearance and protection against
infection. Here we show that vaccination of healthy woodchucks by gene gun bombardment with a plasmid coding for WHcAg (pCw) stimulates proliferation of WHcAg-specific T cells but that these cells do not produce significant levels of
gamma interferon (IFN-gamma) upon
antigen stimulation. In addition, animals vaccinated with pCw alone were not protected against WHV inoculation. In order to induce a Th1
cytokine response, another group of woodchucks was immunized with pCw together with another plasmid coding for woodchuck
interleukin-12 (IL-12). These animals exhibited WHcAg-specific T-cell proliferation with high IFN-gamma production and were protected against challenge with WHV, showing no
viremia or low-level transient
viremia after WHV inoculation. In conclusion, gene gun immunization with WHV core generates a non-Th1 type of response which does not protect against experimental
infection. However, steering the immune response to a Th1
cytokine profile by
IL-12 coadministration achieves protective immunity. These data demonstrate a crucial role of Th1 responses in the control of hepadnavirus replication and suggest new approaches to inducing protection against HBV
infection.