T cell immunopathogenesis and immunotherapeutic strategies for chronic hepatitis B virus infection

Table 1 Immunotherapeutic approaches for animal models of hepatitis B virus infection

Animal model	Immunotherapy	Results	Ref.
Peptide vaccination
HBV transgenic mice	A synthesized fusion peptide, consisting HBcAg18-27 and HIV Tat49-57	Decrease in serum HBV DNA levels and the expression levels of HBsAg and HBcAg in the liver	[40]
Protein vaccination
HBV transgenic mice	HBsAg vaccine	Most of the mice showed reduction of HBV DNA levels and disappearance of HBeAg and HBsAg	[41]
Woodchuck hepatitis virus infection	Combination of vaccine of HBV large surface protein and clevudine	Restoration of T-cell response to Pre-S and S region	[42]
DNA immunization
Acute DHBV infection	DNA vaccine expressing DHBc and Pre-S/S and entecavir Boosted with fowl poxvirus vectors expressing DHBc and Pre-S/S	Clearance of DHBV infection at a rate of 100%	[43]
Chronic DHBV infection	DNA vaccine encoding the HBV large envelope and/or core protein with or without lamivudine	Reduction of viremia and liver DHBV cccDNA in 33% of ducks Seroconversion to anti-pre S in 67% of ducks showing cccDNA clearance	[44]
DC immunization
HBV transgenic mice	Activated bone marrow-derived DCs	Break CTL tolerance to HBsAg	[45]
HBV transgenic mice	Anti-CD40 agonistic monoclonal Ab	Induction of noncytopathic inhibition of HBV replication mediated by antiviral cytokines (IL-12 and TNF-α) produced by activated intrahepatic APCs	[46]
HBV transgenic mice	HBV-specific peptide-pulsed DCs	Reductions in the serum HBsAg and HBV DNA	[47]
Cytokines and adjuvants
HBV transgenic mice	Recombinant IL-12	Marked inhibition of HBV replication in the liver	[48]
HBV transgenic mice	α-galactosylceramide that can activate NK T cells	Complete inhibition of HBV replication	[49]
HBV transgenic mice	Recombinant IL-18	Inhibition of HBV replication noncytopathically, mediated by activation of resident intrahepatic NK cells and NK T cells	[50]
Gene therapy
HBsAg transgenic mice	Lentivectors expressing HBsAg and IgFc fusion Ag	Induction of seroconversion to anti-HBs	[51]

HBV: Hepatitis B virus; DHBV: Duck HBV; DC: Dendritic cell; HBsAg: Hepatitis B surface antigen; HBcAg: Hepatitis B core antigen; HIV: Human immunodeficiency virus; APC: Antigen-presenting cell; IL: Interleukin; NK: Natural killer; CTL: Cytotoxic T lymphocyte; TNF: Tumor necrosis factor; cccDNA: Covalently closed circular DNA; Ab: Antibody; Ag: Antigen.