title: Adoptive transfer of immunity: a new strategy to interfere with severe hepatitis virus reinfection after woodchuck liver transplantation.
abstract: BACKGROUND
  The effective transfer of humoral immunity to hepatitis B virus was first demonstrated after clinical and experimental bone marrow transplantation. This strategy is now evaluated in the woodchuck transplantation model, in which protection from reinfection can be tested.
  
  
  METHODS
  Animals negative for woodchuck hepatitis virus (WHV) (n = 3) were vaccinated using plasmids expressing woodchuck hepatitis virus surface (WHs), woodchuck hepatitis virus core (WHc), and woodchuck interferon-gamma in combination with a protein vaccine (WHs antigen [Ag]) three times before liver donation. Control animals (n= 4) received the liver from non-immunized donors. Chronic WHV carriers served as recipients. The viral load in serum and liver tissue was monitored pretransplant and posttransplant for up to 11 weeks by dot blot, Northern blot, Southern blot, and immunohistochemistry for WHc and WhsAg.
  
  
  RESULTS
  Donor vaccination was effective, as indicated by the development of anti-WHc and anti-WHs antibodies. Transplanting the livers of these donors resulted in a reduction of viral load in two of three animals. No viral DNA was detected in repeated serum samples by dot-blot hybridization technique. However, polymerase chain reaction for viral DNA extracted from serum was always positive. WHV replication intermediates and WHV RNA were absent in repeated liver biopsies. Only few hepatocytes stained weakly positive for WHc protein and frequency, and the intensity of WHsAg positive hepatocytes was low. The third animal developed severe reinfection within 3 weeks, similar to the woodchucks in the control group.
  
  
  CONCLUSIONS
  Liver transplantation from immunized donors to chronic carriers seems to be a promising strategy to reduce and delay severe reinfection, which may be applicable in clinical liver transplantation.
authors.affiliation: Department of General and Transplantation Surgery, University Hospital Essen, Essen, Germany. uta.dahmen@uni-essen.de
authors.forename: Uta
authors.initials: U
authors.lastname: Dahmen
authors.forename: Olaf
authors.initials: O
authors.lastname: Dirsch
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.forename: Melanie
authors.initials: M
authors.lastname: Fiedle
authors.forename: Mengj
authors.initials: M
authors.lastname: Lu
authors.forename: Kai
authors.initials: K
authors.lastname: Rispeter
authors.forename: Martha
authors.initials: M
authors.lastname: Picucci
authors.forename: Christoph E
authors.initials: CE
authors.lastname: Broelsch
authors.forename: Michael
authors.initials: M
authors.lastname: Roggendorf
mesh_terms: D000818:Animals; D004279:DNA, Viral / Q000097:blood; D006509:Hepatitis B / Q000517:prevention & control*; D006510:Hepatitis B Antibodies / Q000097:blood; D017919:Hepatitis B Virus, Woodchuck / Q000276:immunology*; D006801:Humans; D016219:Immunotherapy, Adoptive; D008099:Liver / Q000821:virology; D016031:Liver Transplantation / Q000009:adverse effects; D008392:Marmota; D012367:RNA, Viral / Q000032:analysis; D012008:Recurrence; D014611:Vaccination; D014764:Viral Proteins / Q000032:analysis
chemical_list: D004279:DNA, Viral; D006510:Hepatitis B Antibodies; D012367:RNA, Viral; D014764:Viral Proteins