title: T-helper cell response to woodchuck hepatitis virus antigens after therapeutic vaccination of chronically-infected animals treated with lamivudine.
abstract: OBJECTIVE
  Immunotherapy of patients chronically-infected with hepatitis B virus (HBV) may have the risk of fulminant hepatitis. This risk might be diminished if immunotherapy was carried out under conditions of low viremia.
  
  
  METHODS
  Five woodchucks chronically-infected with woodchuck hepatitis virus (WHV), a virus closely related to HBV, were treated with lamivudine for 23 weeks. At week 10, when viremia had decreased by 3-5 logs, three woodchucks were vaccinated with woodchuck hepatitis virus surface antigen (WHsAg) plus the T-helper determinant FISEAIIHVLHSR.
  
  
  RESULTS
  It was found that the administration of lamivudine only, had no effect on the T-helper response against WHV antigens. By contrast, vaccination induced T-helper responses against WHV antigens, shifting the cytokine profile from Th2 to Th0/Th1, but was without effect on viremia, WHsAg levels, or anti-WHs antibodies. Analysis of liver biopsies showed that lamivudine administration may have reduced hepatic inflammation. By contrast, vaccination clearly enhanced hepatic inflammation. After lamivudine withdrawal, viremia returned to high levels.
  
  
  CONCLUSIONS
  These results suggest that therapeutic vaccination of chronically-infected woodchucks under conditions of low viremia shifts the cytokine profile against viral antigens towards Th0/Th1. This shift may prevent the efficient induction of anti-WHs antibodies.
authors.affiliation: epartamento de Medicina Interna, Facultad de Medicina, Universidad de Navarra, Pamplona, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Hervás-Stubbs
authors.forename: J J
authors.initials: JJ
authors.lastname: Lasarte
authors.forename: P
authors.initials: P
authors.lastname: Sarobe
authors.forename: I
authors.initials: I
authors.lastname: Vivas
authors.forename: L
authors.initials: L
authors.lastname: Condreay
authors.forename: J M
authors.initials: JM
authors.lastname: Cullen
authors.forename: J
authors.initials: J
authors.lastname: Prieto
authors.forename: F
authors.initials: F
authors.lastname: Borrás-Cuesta
mesh_terms: D000818:Animals; D000956:Antigens, Viral / Q000276:immunology*; D002908:Chronic Disease; D006509:Hepatitis B / Q000276:immunology / Q000628:therapy* / Q000821:virology; D017919:Hepatitis B Virus, Woodchuck / Q000187:drug effects / Q000276:immunology*; D016233:Immunotherapy, Active; D019259:Lamivudine / Q000627:therapeutic use*; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008392:Marmota; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D019562:Viral Load; D014766:Viremia / Q000821:virology
chemical_list: D000956:Antigens, Viral; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine