Ubiquitin Conjugation of Hepatitis B Virus Core Antigen DNA Vaccine Leads to Enhanced Cell-Mediated Immune Response in BALB/c Mice
Jian-Hua Chen
1
,
Yong-Sheng Yu
1
,
Hong-Hong Liu
1
,
Xiao-Hua chen
1
,
Min Xi
1
,
Guo-Qing Zang
1
and
Zheng-Hao Tang
2
, *
1 Department of Infectious Diseases, Sixth Peoples Hospital Affiliated to Shanghai Jiaotong University, China
2 Department of Infectious Diseases, Sixth Peoples Hospital Affiliated to Shanghai Jiaotong University, tzhhao@hotmail.com, China
*
Department of Infectious Diseases, Sixth Peoples Hospital Affiliated to Shanghai Jiaotong University, tzhhao@hotmail.com, China. Tel: +86-21643691818673. Fax: +86-2164701361. Email:
tzhhao@hotmail.com
To Cite:
Chen
J, Yu
Y, Liu
H, chen
X, Xi
M, et al. Ubiquitin Conjugation of Hepatitis B Virus Core Antigen DNA Vaccine Leads to Enhanced Cell-Mediated Immune Response in BALB/c Mice,
Hepat Mon.
Online ahead of Print
;11(8):620-628.
doi: 10.5812/kowsar.1735143X.689 .
Abstract
Background: Nearly 350 million persons worldwide are chronically infected with hepatitis B virus (HBV). Ubiquitin (Ub) is a highly conserved small regulatory protein, ubiquitous in eukaryotes, that usually serves as a signal for the target protein that is recognised and degraded in proteasomes . The Ub-mediated processing of antigens is rapid and efficient and stimulates cell-mediated immune responses. Accordingly, Ub-mediated processing of antigens has been widely used in chronic-infection and cancer studies to improve immune response.Objectives: Many clinical trials have shown that DNA vaccine potency needs to be greatly enhanced. Here, we report a new strategy for designing an HBV DNA vaccine using the ubiquitin (Ub) sequence. The aim of this study was to investigate a novel DNA vaccination, based on the expression of HBV core antigen (HBcAg), fused to Ub to enhance DNA vaccine potency.Materials and Methods: Mouse ubiquitin fused to the HBcAg gene and cloned into the eukaryotic vector pcDNA3.1 (-). BALB/c mice were immunized with recombinant pUb-HBcAg or pHBcAg DNA vaccine. Lymphocyte proliferation assay, intracellular IFN-γ assay, CTL cytotoxicity assay, and antibody assay were performed to analyze the cellular and humoral immune responses to our DNA constructs.Results: HBcAg was expressed effectively in the COS-7 cells that were transiently transfected with pUb-HBcAg. Strong anti-HBc IgG responses were elicited in mice that were immunized with pUb-HBcAg. The endpoint titers of anti-HBc peaked at 1:656100 on the 42nd day after the third immunization. pUb-HBcAg stimulated greater lymphocyte proliferation and induced higher levels of IL-2 and IFN-γ and a greater percentage of HBcAg-specific CD8+ T cells in mice than pHBcAg. In the CTL assay, the specific lysis rate reached 56.5% at an effector:target ratio of 50:1 in mice that were immunized with pUb-HBcAg.Conclusions: pUb-HBcAg elicits specific anti-HBc responses and induces HBc-specific CTL responses in immunized BALB/c mice. Our results imply that Ub can be used as a molecular adjuvant that enhances the potency of DNA vaccines.Keywords: DNA vaccine; Ubiquitin; Hepatitis B core antigen
Please cite this paper as: Chen JH, Yu YS, Liu HH, Chen XH, Xi M, Zang GQ, et al. Ubiquitin Conjugation of Hepatitis B Virus Core Antigen DNA Vaccine Leads to Enhanced Cell-Mediated Immune Response in BALB/c Mice. Hepat Mon. 2011;11(8):620-8. [DOI: 10.5812/kowsar.1735143X.689]
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