The woodchuck as an animal model for pathogenesis and therapy of chronic hepatitis B virus infection

Table 2 Immunotherapeutic approaches in the woodchuck model of chronic HBV infection

Treatment	Outcome	Additional results	Ref.
Vaccination
WHsAg vaccine/adjuvant	Anti-WHs response	CMI to WHsAg	[55,56,155]
WHsAg vaccine/adjuvant	Anti-WHs response (antibodies mainly directed against preS region)		[173]
WHsAg vaccine/Th peptide epitope	Anti-WHs response	Two woodchucks died	[174]
	Transient serum WHV DNA red. in a few animals (1 log)
Cytokines
IFN-α (adenoviral vector)	Transient serum WHV DNA red. (1 log)	Transient WHV RI red. (1 log)	[181]
IFN-α (adeno-associated viral vector)	Transient serum WHV DNA red. (2 logs)		[182]
	Sustained serum WHV DNA red. in 2 animals
IFN-γ (adenoviral vector)	No antiviral effect		[181]
Adoptive immunotransfer
Liver transplantation	Serum WHV DNA red.	WHV RI red., WHV RNA red.	[188]
Combination treatment
Lamivudine + WHsAg vaccine/ Th peptide epitope	No additional benefit beyond lamivudine-induced antiviral effect	CMI to WHsAg/WHcAg
Lamivudine + β-galactosidase (adenoviral vector)	Transient but sustained serum WHV DNA red. (> 1 log) in addition to lamivudine-induced antiviral effect	WHV RI red., WHV cccDNA red., WHV RNA red.	[191]
Clevudine + β-galactosidase/+ IFN-γ/+ IFN-α (adenoviral vector)	Transient but sustained serum WHV DNA red. in addition to clevudine-induced antiviral effect	WHV RI red.	[156]
Clevudine + emtricitabine + IFN-γ (adenoviral vector)	No additional benefit beyond clevudine + emtricitabine-induced antiviral effect	Increased liver inflammation with IFN-γ	[150]
Clevudine + WHsAg vaccine	Anti-WHs response	WHV cccDNA red.,	[55,56,155]
	Sustained serum WHV DNA red. (> 6 to 8 log)	CMI to WHsAg/WHcAg
		Delay in onset of disease progression

WHV RI, hepatic WHV DNA replicative intermediates; WHV cccDNA, covalently closed circular WHV DNA, WHV RNA, intrahepatic WHV RNA; red., reduction.