Induction and maintenance of anti-HBs in immunosuppressed murine hepatitis B virus carriers by a novel vaccination approach: implications for use in hepatitis B virus-infected subjects with liver transplantation.
BACKGROUND
One of the major problems with orthotopic liver transplantation (OLT) in patients with endstage liver diseases due to hepatitis B virus (HBV) is to maintain sustained high levels of antibody to hepatitis B surface antigen (anti-HBs) to block reactivation of HBV infection and allograft rejection. The aim of this study was to induce anti-HBs by a unique vaccination protocol, using hepatitis B surface antigen (HBsAg)-pulsed dendritic cells (DCs) in immunosuppressed murine HBV carriers.


METHODS
Immunosuppressed murine HBV carriers were produced by injecting FK-506 (2 mg/kg), intraperitoneally, daily for 15 days in HBV-transgenic mice (Tg) expressing HBV-related mRNAs and proteins. HBsAg-pulsed DCs were prepared by culturing murine spleen DCs with HBsAg (100 microg) for 24 h. HBsAg-pulsed DCs were injected twice, at an interval of 2 weeks, to immunosuppressed HBV-Tg and the levels of anti-HBs were measured periodically for 4 months.


RESULTS
Injection with FK-506 resulted in the production of immunosuppressed HBV-Tg, as evident by their low production of cytokine mRNAs and proteins. Two injections of HBsAg-pulsed DCs from immunosuppressed HBV-Tg induced anti-HBs in all immunosuppressed HBV-Tg within 4-8 weeks after the second injection. More than 10 IU/l of anti-HBs was detected in the sera in all but one immunosuppressed HBV-Tg for more than 4 months, although all immunosuppressed HBV-Tg were continuously provided with FK-506 on a daily basis for the entire duration of the study.


CONCLUSIONS
The capacity of HBsAg-pulsed DCs to induce anti-HBs in immunosuppressed HBV-Tg inspires optimism for the possible use of this therapeutic regimen for HBV-infected OLT patients.
Furukawa
Shinya
S
Third Department of Internal Medicine, Ehime University School of Medicine, 791-0295 Ehime, Shigenobu-Cho, Onsen-Gun, Japan.
Akbar
Sk Md Fazle
SM
Hasebe
Aki
A
Horiike
Norio
N
Onji
Morikazu
M
D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology*; D006510:Hepatitis B Antibodies / Q000096:biosynthesis*; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D007108:Immune Tolerance; D016031:Liver Transplantation; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D014611:Vaccination / Q000379:methods
D001323:Autoantibodies; D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines