Chemoimmunotherapy of chronic hepatitis B virus infection in the woodchuck model overcomes immunologic tolerance and restores T-cell responses to pre-S and S regions of the viral envelope protein.
Treatment of chronic hepatitis B virus (HBV) infection could combine potent antiviral drugs and therapeutic vaccines to overcome immunological tolerance and induce the recovery phenotype to protect against disease progression. Conventional vaccination of woodchucks chronically infected with the woodchuck hepatitis virus (WHV) elicited differential T-cell response profiles depending on whether or not carriers were treated with the potent antiviral drug clevudine (CLV), which significantly reduces viral and antigen loads. The differential T-cell responses defined both CLV-dependent and CLV-independent epitopes of the pre-S and S regions of the WHV envelope protein. Only combined treatment involving CLV and conventional vaccine therapeutically restored the T-cell response profile of chronic WHV carrier woodchucks to that seen in prophylactic vaccination and in recovery from acute WHV infection. The results have implications for mechanisms of immunological tolerance operating in chronic HBV infection and suggest that such combined chemoimmunotherapy may be useful for treatment of humans with chronic HBV infection.
Menne
Stephan
S
Gastrointestinal Unit, Department of Clinical Sciences, College of Veterinary Medicine, Room C-2005 VMC, Cornell University, Ithaca, New York 14853, USA. sm119@cornell.edu
Tennant
Bud C
BC
Gerin
John L
JL
Cote
Paul J
PJ
D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use*; D001086:Arabinofuranosyluracil / Q000031:analogs & derivatives* / Q000627:therapeutic use; D002353:Carrier State; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D005260:Female; D006510:Hepatitis B Antibodies / Q000276:immunology; D006514:Hepatitis B Surface Antigens / Q000737:chemistry / Q000276:immunology; D017325:Hepatitis B Vaccines / Q000627:therapeutic use*; D017919:Hepatitis B Virus, Woodchuck; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000628:therapy; D007108:Immune Tolerance; D007167:Immunotherapy; D008392:Marmota / Q000276:immunology* / Q000821:virology; D013601:T-Lymphocytes / Q000276:immunology; D014611:Vaccination; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000276:immunology
D000998:Antiviral Agents; D000939:Epitopes; D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D014759:Viral Envelope Proteins; D001086:Arabinofuranosyluracil; C034935:clevudine