Production and efficacy of a dendritic cell-based therapeutic vaccine for murine chronic hepatitis B virus carrierer.
Recently a new field of immunological research and clinical application of vaccines for therapeutic purposes (vaccine therapy) has been developed for treating several chronic viral infections including chronic hepatitis B virus (HBV) infection. Administration of vaccine containing hepatitis B surface antigen (HBsAg) for 1 year has resulted in negative HBsAg and development of antibody to HBsAg (anti-HBs) in some, but not in all, HBV transgenic mouse (HBV-Tg). In order to develop more potent regimen of vaccine therapy for chronic HBV carrier, we prepared a dendritic cell (DC)-based therapeutic vaccine and evaluated their therapeutic potential in HBV-Tg. DCs were isolated from single cell suspensions of murine spleen cells by collagenase digestion, density centrifugation and depletion of lymphocytes. Spleen DCs were cultured with HBsAg (100 microg) for 24 h to produce HBsAg-pulsed DCs. HBV-Tg expressing HBsAg and HBV DNA in the sera were randomly assigned to receive either HBsAg-pulsed DCs (n = 20) or unpulsed DC (n = 20) or vaccine containing HBsAg (n = 39) or complete Freund's adjuvant (n = 20) or left untreated (n = 20). Only two intraperitoneal injections of HBsAg-pulsed DCs resulted in negative HBsAg and production of anti-HBs in the sera in all HBV-Tg (n = 20). However, administration of un-pulsed DCs (n = 20) or vaccine containing HBsAg (n = 39) or only complete Freund's adjuvant did not induce negative HBsAg or production of anti-HBs in any HBV-Tg within 6 months of therapy commencement. Taken together, this study showed that HBsAg-pulsed DCs represent a highly potent therapeutic vaccine for chronic HBV infection and inspire optimism of using this vaccine in clinical conditions. A clinical trial of HBsAg-pulsed DC in patients with chronic hepatitis B is warranted.
Akbar
S M F
SM
Third Department of Internal Medicine, Ehime University School of Medicine, Ehime, Japan.
Furukawa
Shinya
S
Hasebe
Aki
A
Horiike
Norio
N
Michitaka
Kojiro
K
Onji
Morikazu
M
D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis; D002499:Centrifugation, Density Gradient; D017364:Collagenases / Q000378:metabolism; D003713:Dendritic Cells / Q000378:metabolism*; D006514:Hepatitis B Surface Antigens / Q000737:chemistry; D017325:Hepatitis B Vaccines; D006515:Hepatitis B virus / Q000378:metabolism*; D007108:Immune Tolerance; D007167:Immunotherapy / Q000379:methods; D007700:Kinetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010641:Phenotype; D013154:Spleen / Q000166:cytology; D013997:Time Factors; D014611:Vaccination / Q000379:methods; D014612:Vaccines
D001323:Autoantibodies; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D014612:Vaccines; D017364:Collagenases