BACKGROUND/AIMS: 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.
BACKGROUND/AIMS: 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.
Authors: Pham Thi Le Hoa; Nguyen Tien Huy; Le The Thu; Cao Ngoc Nga; Kazuhiko Nakao; Katsumi Eguchi; Nguyen Huu Chi; Bui Huu Hoang; Kenji Hirayama Journal: Antimicrob Agents Chemother Date: 2009-09-21 Impact factor: 5.191