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本帖最后由 肝胆速递 于 2012-9-23 00:23 编辑
http://www.sciencedirect.com/science/article/pii/S0166354212001726
Antiviral Research
Volume 96, Issue 1, October 2012, Pages 59–64
Strong and multi-antigen specific immunity by hepatitis B core antigen (HBcAg)-based vaccines in a murine model of chronic hepatitis B: HBcAg is a candidate for a therapeutic vaccine against hepatitis B virus
Sheikh Mohammad Fazle Akbar a, Corresponding author contact information, E-mail the corresponding author,
Shiyi Chen b, E-mail the corresponding author,
Mamun Al-Mahtab c, E-mail the corresponding author,
Masanori Abe b, E-mail the corresponding author,
Yoichi Hiasa b, E-mail the corresponding author,
Morikazu Onji b, E-mail the corresponding author
a Department of Medical Sciences, Toshiba General Hospital, Higashi Oi 6-3-22, Shinagawa, Tokyo 140-8522, Japan
b Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Ehime, Toon City, Ehime 791-0295, Japan
c Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Shahbagh, Dhaka 1000, Bangladesh
Abstract
Experimental evidence suggests that hepatitis B core antigen (HBcAg)-specific cytotoxic T lymphocytes (CTL) are essential for the control of hepatitis B virus (HBV) replication and prevention of liver damage in patients with chronic hepatitis B (CHB). However, most immune therapeutic approaches in CHB patients have been accomplished with hepatitis B surface antigen (HBsAg)-based prophylactic vaccines with unsatisfactory clinical outcomes. In this study, we prepared HBsAg-pulsed dendritic cells (DC) and HBcAg-pulsed DC by culturing spleen DC from HBV transgenic mice (HBV TM) and evaluated the immunomodulatory capabilities of these antigens, which may serve as a better therapy for CHB. The kinetics of HBsAg, antibody levels against HBsAg (anti-HBs), proliferation of HBsAg- and HBcAg-specific lymphocytes, production of antigen-specific CTL, and activation of endogenous DC were compared between HBV TM vaccinated with either HBsAg- or HBcAg-pulsed DC. Vaccination with HBsAg-pulsed DC induced HBsAg-specific immunity, but failed to induce HBcAg-specific immunity in HBV TM. However, immunization of HBV TM with HBcAg-pulsed DC resulted in: (1) HBsAg negativity, (2) production of anti-HBs, and (3) development of HBsAg- and HBcAg-specific T cells and CTL in the spleen and the liver. Additionally, significantly higher levels of activated endogenous DC were detected in HBV TM immunized with HBcAg-pulsed DC compared to HBsAg-pulsed DC (p < 0.05). The capacity of HBcAg to modulate both HBsAg- and HBcAg-specific immunity in HBV TM, and activation of endogenous DC in HBV TM without inducing liver damage suggests that HBcAg should be an integral component of the therapeutic vaccine against CHB.
Highlights
► HBsAg and HBcAg-pulsed dendritic cells (DC) were prepared as therapeutic vaccine.
► HBsAg induced HBsAg-specific, but not HBcAg-specific, immune responses in HBV TM.
► HBcAg induced strong HBcAg and HBsAg-specific humoral and cellular immunity in HBV TM.
► HBcAg-based vaccine activated endogenous dendritic cells of HBV TM.
► HBcAg should be incorporated in therapeutic vaccine for treatment of chronic HBV.
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