Mechanism of action of vaccine therapy in murine hepatitis B virus carriers: vaccine-induced activation of antigen presenting dendritic cells.
OBJECTIVE
Vaccine therapy in which vaccine containing hepatitis B surface antigen (HBsAg) is injected has shown therapeutic activity (vaccine therapy) in some human and murine chronic hepatitis B virus (HBV)-carriers. Using HBV-transgenic mice (HBV-Tg), an animal model of the HBV-carrier state, the mechanism underlying the antiviral and immune modulatory capacity of vaccine therapy was studied.


METHODS
Placebo-controlled, double-blind trials of vaccine therapy were conducted in HBV-Tg; some HBV-Tg responded to the therapy, whereas others were non-responders. The titers of HBV-markers, the functions of lymphocytes and antigen presenting dendritic cells were compared between vaccine responders and vaccine non-responders.


RESULTS
The prevaccinated titers of HBsAg, hepatitis B e-antigen (HBeAg), HBV DNA and the responses of lymphocytes to polyclonal mitogens were almost unchanged between responders and non-responders, but the levels of proliferation of HBsAg-specific lymphocytes from non-responders was significantly lower than responders (p<0.05). The capacity of dendritic cells to induce proliferation of T cells and production of antibody to HBsAg (anti-HBs) was significantly higher in responders compared with non-responders (p<0.05). Injection with HBsAg resulted in upregulation of MHC class II and CD86 antigens (p<0.05) on dendritic cells and increased production of IL-12, IL-2 and TNF-alpha in cultures (p<0.05) in vaccine responders but not in non-responders.


CONCLUSIONS
The activation of dendritic cells following injection with vaccine containing HBsAg is the vital factor underlying the therapeutic potentiality of vaccine therapy in HBV carriers.
Akbar
S M
SM
Third Department of Internal Medicine, Ehime University School of Medicine, Japan.
Abe
M
M
Masumoto
T
T
Horiike
N
N
Onji
M
M
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D001402:B-Lymphocytes / Q000276:immunology; D051940:B7-2 Antigen; D002353:Carrier State / Q000276:immunology*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D004311:Double-Blind Method; D006509:Hepatitis B / Q000276:immunology*; D006510:Hepatitis B Antibodies / Q000097:blood*; D006514:Hepatitis B Surface Antigens / Q000276:immunology; D017325:Hepatitis B Vaccines / Q000276:immunology* / Q000494:pharmacology; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D006801:Humans; D018664:Interleukin-12 / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D013601:T-Lymphocytes / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D015703:Antigens, CD; D051940:B7-2 Antigen; C497964:CD86 protein, human; C497965:Cd86 protein, mouse; D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D000949:Histocompatibility Antigens Class II; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12