Immune modulator and antiviral potential of dendritic cells pulsed with both hepatitis B surface antigen and core antigen for treating chronic HBV infection.
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.
Akbar
Sheikh Mohammad Fazle
SM
Department of Medical Sciences, Toshiba General Hospital, Tokyo, Japan. sheikh.akbar@po.toshiba.co.jp
Yoshida
Osamu
O
Chen
Shiyi
S
Cesar
Aguilar Julio
AJ
Abe
Masanori
M
Matsuura
Bunzo
B
Hiasa
Yoichi
Y
Onji
Morikazu
M
D000328:Adult; D000818:Animals; D000998:Antiviral Agents / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D006510:Hepatitis B Antibodies / Q000097:blood / Q000276:immunology; D006512:Hepatitis B Core Antigens / Q000276:immunology*; D006514:Hepatitis B Surface Antigens / Q000276:immunology*; D017325:Hepatitis B Vaccines / Q000276:immunology*; D019694:Hepatitis B, Chronic / Q000276:immunology / Q000517:prevention & control*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008875:Middle Aged; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014611:Vaccination; D055815:Young Adult
D000998:Antiviral Agents; D006510:Hepatitis B Antibodies; D006512:Hepatitis B Core Antigens; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines