Recombinant heat shock protein 65 carrying PADRE and HBV epitopes activates dendritic cells and elicits HBV-specific CTL responses.
BCG Hsp65 and PADRE have been shown to be potent to enhance antigen specific immunity. In order to explore the possibility to utilize them for the development of HBV therapeutic vaccine, a chimeric protein, Hsp65-HBV, was created by fusing PADRE and epitopes from HBV to the carboxyl-terminus of BCG Hsp65 and expressed in E. coli. We evaluated its effects on human dendritic cell maturation and specific CTL induction in vitro. Results showed that Hsp65-HBV could activate human dendritic cells by up-regulating the expressions of HLA-A2, HLA-DR and CD86, companioning with high level of IL-12 secretion. Furthermore, Hsp65-HBV matured DCs could significantly stimulate human autologous CD8(+) T cell proliferation and induce HBV-specific CTLs. Hsp65-HBV was also shown to generate HBsAg-specific CTLs in vivo in mice. These results indicated that Hsp65-HBV might be a candidate for the treatment of chronic HBV infection.
Department of Molecular Biology, Norman Bethune Medical College, Jilin University, Changchun 130021, PR China.
Hua
H
Wang
Xuejin
X
Su
Peiyin
P
Zhang
Ji
J
Liang
Hongfei
H
Wei
Min
M
Wan
Xiuli
X
Wu
Yongli
Y
Yu
Liying
L
Wang
D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000276:immunology*; D000939:Epitopes / Q000235:genetics / Q000276:immunology; D004926:Escherichia coli / Q000235:genetics; D005260:Female; D006360:Heat-Shock Proteins / Q000235:genetics / Q000276:immunology*; D006509:Hepatitis B / Q000276:immunology / Q000517:prevention & control*; D017325:Hepatitis B Vaccines / Q000276:immunology*; D006515:Hepatitis B virus / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D018664:Interleukin-12 / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D018834:Chaperonin 60; D024101:Mitochondrial Proteins
D000939:Epitopes; D006360:Heat-Shock Proteins; D017325:Hepatitis B Vaccines; D007371:Interferon-gamma; D018664:Interleukin-12; D011993:Recombinant Fusion Proteins; C060293:HSPD1 protein, human; D018834:Chaperonin 60; D024101:Mitochondrial Proteins