Review Article

Therapeutic Vaccination in Chronic Hepatitis B: Preclinical Studies in the Woodchuck

Table 3

Studies on gene therapy of chronic hepatitis and HCC in the woodchuck model.

VectorApplicationOutcome>Reference

Helper-dependent AdV expressing woodchuck IFN Intravenous (portal vein)Transient inhibition of WHV replicationFiedler et al., 2004 [163]
Helper-dependent AdV expressing woodchuck IFN Intravenous (portal vein)No effectFiedler et al., 2004 [163]
AdV expressing woodchuck IFN in combination with clevudine (L-FMAU) and emtricitabine (FTC)intravenousT-cell infiltration and inflammation in the liver Jacquard et al., 2004 [164]
No additional antiviral effect beyond the treatment with the nucleot(s)ide analogues
AdV expressing woodchuck IFN and TNF in combination with clevudine (L-FMAU)intravenousTransient inhibition of WHV replicationZhu et al., 2004 [165]
High-capacity AdV expressing murine IL-12 under the control of a liver-specific inducible promoterintrahepatic (via laparotomy)Inhibition of WHV replication in the liver and decreased viral load in serum. Crettaz et al., 2009 [166]
Induction of anti-WHs antibodies.
The effect was observed only in animals with basal viremia lower than 1010 copies/mL.
AdV expressing herpes simplex virus thimidine kinase combined with gancyclovir treatmentintratumoural (via laparotomy)Necrotic areas in the tumour mass and in the liver. Bilbao et al., 2000 [167]
No reduction in tumour volume.
AdV expressing murine IL-12 and B7.1 moleculeintratumoural (via laparotomy and MRI guidance)CD4+ and CD8+ T cell infiltration in the liver. Pützer et al., 2001 [168]
Reduction in tumour volume.
Semliki forest viral vector expressing murine IL-12intratumoural (via laparotomy)Induction of T cell responses to tumour antigens. Rodriguez-Madoz et al., 2009 [75]
Induction T cell responses to WHcAg and WHsAg.
Dose-dependent, transient reduction in tumour volume.