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

Abstract

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.

• Authors: Sheikh Mohammad Fazle Akbar, Osamu Yoshida, Shiyi Chen, Aguilar Julio Cesar, Masanori Abe, Bunzo Matsuura, Yoichi Hiasa, Morikazu Onji
• Journal: Antiviral therapy (Antivir Ther) Vol. 15 Issue 6 Pg. 887-95 ( 2010) ISSN: 2040-2058 [Electronic] England
• PMID: 20834101 (Publication Type: Journal Article)

Chemical References

• Antiviral Agents
• Hepatitis B Antibodies
• Hepatitis B Core Antigens
• Hepatitis B Surface Antigens
• Hepatitis B Vaccines

Topics

• Adult
• Animals
• Antiviral Agents (immunology)
• Cells, Cultured
• Dendritic Cells (immunology, metabolism)
• Hepatitis B Antibodies (blood, immunology)
• Hepatitis B Core Antigens (immunology)
• Hepatitis B Surface Antigens (immunology)
• Hepatitis B Vaccines (immunology)
• Hepatitis B, Chronic (immunology, prevention & control)
• Humans
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Transgenic
• Middle Aged
• Spleen (cytology, immunology)
• T-Lymphocytes (immunology)
• Vaccination
• Young Adult