The delivery of HBcAg via Tat-PTD enhances specific immune response and inhibits Hepatitis B virus replication in transgenic mice.
Recent studies have indicated that the therapeutic vaccine based on enhancement of HBV-specific cytotoxic T-lymphocyte (CTL) activity may lead to viral clearance in chronically infected individuals. It is demonstrated that protein transduction domains (PTD) from HIV-1-Tat protein is able to enter cells when combined with exogenous antigens and induce specific CTL responses. We have previously testified that the expressed and purified fusion protein containing Tat-PTD47-57 and HBcAg could enter cytoplasm of dendritic cells, and enhance T cells response to generate HBcAg-specific CTLs efficiently in vitro. In the present study, we evaluated HBcAg-specific immune responses of PTD-HBcAg fusion protein in BALB/c mice and antiviral immunity in HBV transgenic mice. The studies showed that PTD-HBcAg not only induced significantly higher antibody responses, but also increased production of cytokine (IFN-gamma, IL-2, IL-4 and IL-10) compared to HBcAg alone and PBS. Moreover, PTD-HBcAg fusion protein increased significantly the percentages of IFN-gamma+CD8+ T cells and HBcAg-specific (CTL) responses. Also, enhancement of immune response induced by fusion protein reduced HBV DNA and HBsAg levels and decreased the expression of HBsAg in liver tissue of HBV transgenic mice. In conclusion, PTD-HBcAg fusion protein could enhance not only cell immune response but also humoral immune response, and induce robust specific CTL activity and therapeutic effects in HBV transgenic mice.
Chen
Xiaohua
X
Department of Infectious Disease, Shanghai No.6 People's Hospital, College of Medicine, Shanghai JiaoTong University, Shanghai 200233, China.
Lai
Jinglan
J
Pan
Qingchun
Q
Tang
Zhenghao
Z
Yu
Yongsheng
Y
Zang
Guoqing
G
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D006508:Hepatitis Antibodies / Q000097:blood; D006509:Hepatitis B / Q000276:immunology* / Q000517:prevention & control*; D006512:Hepatitis B Core Antigens / Q000276:immunology*; D006515:Hepatitis B virus / Q000502:physiology*; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D007371:Interferon-gamma / Q000276:immunology; D008099:Liver / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D011993:Recombinant Fusion Proteins / Q000276:immunology; D013154:Spleen / Q000276:immunology; D014779:Virus Replication; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000276:immunology
D006508:Hepatitis Antibodies; D006512:Hepatitis B Core Antigens; D011993:Recombinant Fusion Proteins; D054322:tat Gene Products, Human Immunodeficiency Virus; D007371:Interferon-gamma