Ubiquitin Conjugation of Hepatitis B Virus Core Antigen DNA Vaccine Leads to Enhanced Cell-Mediated Immune Response in BALB/c Mice

authors:

avatar Jian-Hua Chen 1 , avatar Yong-Sheng Yu 1 , avatar Hong-Hong Liu 1 , avatar Xiao-Hua chen 1 , avatar Min Xi 1 , avatar Guo-Qing Zang 1 , avatar Zheng-Hao Tang 2 , *

Department of Infectious Diseases, Sixth Peoples Hospital Affiliated to Shanghai Jiaotong University, China
Department of Infectious Diseases, Sixth Peoples Hospital Affiliated to Shanghai Jiaotong University, tzhhao@hotmail.com, China
Hepatitis Monthly: Vol.11, issue 8; 620-628
article type: Research Article
received: February 24, 2011
accepted: April 1, 2011
DOI: https://doi.org/10.5812/kowsar.1735143X.689

how 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. 2011;11(8): 620-628. https://doi.org/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

  • Implication for health policy/practice/research/medical education:
    This strategy may have therapeutic value that can be applied to the treatment of infectious diseases.
  • 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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