Induction of Tc1 response and enhanced cytotoxic T lymphocyte activity in mice by dendritic cells transduced with adenovirus expressing HBsAg.
We evaluated the potential of dendritic cells (DCs) engineered to express antigen of hepatitis B virus (HBV) in priming Th/Tc and HBV-specific CTL responses in mice. Recombinant adenovirus expressing hepatitis B surface antigen (HBsAg) (Ad-S) was constructed, and bone marrow-derived DCs were transduced with Ad-S or pulsed with HBsAg protein. Mice were injected with either Ad-S-transduced DCs or HBsAg-pulsed DCs or plasmid DNA encoding HBsAg twice at 3-week intervals. We showed that adenovirus infection had no further effect on the phenotype, the ability to induce IFN-gamma-producing Th1/Tc1 response or the T cell stimulatory capacity of already mature DCs in vitro. We also showed that immunization with Ad-S-transduced DCs effectively induced Tc1 cells and HBsAg-specific CTLs in vivo and down-regulated the circulating HBsAg and HBV DNA in HBV transgenic mice. Furthermore, these efficacies were stronger than that of HBsAg-pulsed DCs and plasmid DNA. Thus, DCs transduced with recombinant adenovirus may be a promising candidate for an effective CTL-based therapeutic vaccine against HBV.
Institute of Infectious Diseases, First Affiliated Hospital, Medical College, Zhejiang University, Qingchun Road 79, Hangzhou 310003, China.
Yin
Y
Huang
Zhi
Z
Chen
Hongyu
H
Jia
Wei
W
Wu
Shigen
S
Zhong
Cheng
C
Zhou
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D004279:DNA, Viral / Q000097:blood; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006509:Hepatitis B / Q000517:prevention & control; D006514:Hepatitis B Surface Antigens / Q000097:blood / Q000235:genetics* / Q000276:immunology*; D007114:Immunization; D007371:Interferon-gamma / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D013154:Spleen / Q000166:cytology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014161:Transduction, Genetic; D019444:Vaccines, DNA
D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D019444:Vaccines, DNA; D015847:Interleukin-4; D007371:Interferon-gamma