BACKGROUND: Hepatitis B virus infection is a major problem in liver transplantation. In this study, we examined the potential efficay of a recombinant adenovirus expressing an antibody against the HBV preS2 antigen (Ab-H-HBV-S2) in preventing HBV recurrent infection after liver transplantation. METHODS: A gene for humanized antibody against the HBV preS2 antigen was cloned into pDC315, a type 5 adenoviral shuttle plasmid. Recombinant virus was obtained by homologous recombination in the 293 packaging cells. The virus containing the Ab-H-HBV-S2 gene was transduced into the rat liver graft during cold preservation. The recombinant virus produced antibody and showed protective effects on human hepatocytes from hepatitis B virus infection in vitro. RESULTS: The recombinant virus titer determined by TCID50 analysis was 5.1x10(10) PFU/mL. The concentration of preS2 antibody in BALB/C nude mice was 16.7 +/- 10.5 microg/mL on day 3,30.9 +/- 13.6 pg/mL on day 7, and lasted for 5 weeks after the injection. At a concentration of 0.5 microg/mL or above, the preS2 antibody protected cultured human hepatocytes from hepatitis B virus. CONCLUSIONS: Adenovirus-mediated gene transduction of anti-preS2 antibody in the transplanted liver may be a useful approach to prevent hepatitis B infection after liver transplantation.
BACKGROUND:Hepatitis B virus infection is a major problem in liver transplantation. In this study, we examined the potential efficay of a recombinant adenovirus expressing an antibody against the HBV preS2 antigen (Ab-H-HBV-S2) in preventing HBV recurrent infection after liver transplantation. METHODS: A gene for humanized antibody against the HBV preS2 antigen was cloned into pDC315, a type 5 adenoviral shuttle plasmid. Recombinant virus was obtained by homologous recombination in the 293 packaging cells. The virus containing the Ab-H-HBV-S2 gene was transduced into the rat liver graft during cold preservation. The recombinant virus produced antibody and showed protective effects on human hepatocytes from hepatitis B virus infection in vitro. RESULTS: The recombinant virus titer determined by TCID50 analysis was 5.1x10(10) PFU/mL. The concentration of preS2 antibody in BALB/C nude mice was 16.7 +/- 10.5 microg/mL on day 3,30.9 +/- 13.6 pg/mL on day 7, and lasted for 5 weeks after the injection. At a concentration of 0.5 microg/mL or above, the preS2 antibody protected cultured human hepatocytes from hepatitis B virus. CONCLUSIONS: Adenovirus-mediated gene transduction of anti-preS2 antibody in the transplanted liver may be a useful approach to prevent hepatitis B infection after liver transplantation.