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Original article

Immune modulator and antiviral potential of dendritic cells pulsed with both hepatitis B surface antigen and core antigen for treating chronic HBV infection

Sheikh Mohammad Fazle Akbar, Osamu Yoshida, Shiyi Chen, Aguilar Julio Cesar, Masanori Abe, Bunzo Matsuura, Yoichi Hiasa, Morikazu Onji

Corresponding author name: Sheikh Mohammad Fazle Akbar
Corresponding author e-mail: sheikh.akbar@po.toshiba.co.jp

Citation: Antiviral Therapy 2010; 15:887-895
doi: 10.3851/IMP1637

Date accepted: 25 March 2010
Date published online: 20 August 2010


Background: Commercially available prophylactic vaccines containing hepatitis B surface antigen (HBsAg), which are used to prevent HBV infections, are not as effective as a therapeutic immune modulator for treating patients with chronic hepatitis B (CHB). In this study, the immunogenicity of dendritic cells (DC) loaded with both HBsAg and hepatitis B core antigen (HBcAg) was tested in HBV transgenic mice (TM; 1.2HB-BS10) in vivo and in patients with CHB in vitro.

Methods: Spleen DC from HBV TM were cultured with a vaccine containing both HBsAg and HBcAg to produce HBsAg/HBcAg-pulsed DC. HBV TM were immunized twice at an interval of 4 weeks with HBsAg/HBcAg-pulsed DC and other immune modulators. Antibody titres to HBsAg (anti-HBs) were measured in sera. Antigen-specific T-cells and cytotoxic T-lymphocytes (CTLs) in the spleen and liver were detected by lymphoproliferative and ELISPOT assays, respectively. HBsAg/HBcAg-pulsed human blood DC were cultured with autologous T-cells from CHB patients to assess their antigen-specific immune modulatory capacities.

Results: Significantly higher levels of anti-HBs, HBsAg-specific and HBcAg-specific T-cells and CTLs were detected in the spleen and liver of HBV TM immunized with HBsAg/HBcAg-pulsed DC compared with those immunized with other vaccine formulations (P<0.05). HBsAg/HBcAg-pulsed human blood DC also induced HBsAg- and HBcAg-specific proliferation of autologous T-cells from CHB patients.

Conclusions: The immune modulatory capacities of HBsAg/HBcAg-pulsed DC in HBV TM in vivo, and in patients with CHB in vitro, inspire optimism about a clinical trial with this cell-based vaccine in patients with CHB.


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