The Wild-Type Hepatitis C Virus Core Inhibits Initiation of Antigen-Specific T- and B-Cell Immune Responses in BALB/c Mice

Zhu, Wenbo; Chang, Yanzi; Wu, Chunchen; Han, Qingxia; Pei, Rongjuan; Lu, Mengji; Chen, Xinwen

doi:10.1128/cvi.00490-09

Cited by 17 publications

(27 citation statements)

References 53 publications

(71 reference statements)

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“…The vectors expressing partial or full length of core and NS3 genes from HCV have been exploited for vaccine purposes routinely due to their suitable immunogenicity and high homology among HCV genotypes (3,7,33,34). Recent publications reported significant controversy regarding to usefulness of full length core protein as vaccine antigen (20,21,24,26,29,35). Some groups of scientists started to use partial fragments of core gene instead of full length genome to overcome shortcomings reported to be associated with the full size core gene such as immunomodulatory and autoimmunity effects (18,24,26).…”

Section: Discussionmentioning

confidence: 99%

“…However recently published studies demonstrated that both C-and N-terminal domain of HCV core contain autoimmune inducing sequences that maybe harmful for vaccine design (24). Also other studies had shown the immune suppression effect of core protein in animal models and defect of full core gene on immune induction in addition to usefulness of truncated form of core for vaccine purposes (18,(25)(26)(27)(28)(29). In this project, we prepared new expressing vector containing a truncated core gene without Nand C-terminal domain to avoid autoimmunity and/or immune modulatory effects of full length gene.…”

Section: Introductionmentioning

confidence: 99%

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Construction of an Expression Vector Containing a Novel Fusion Sequence from Middle Region of NS3 and Truncated Core Genes of Hepatitis C Virus

et al. 2010

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Background and Aims: DNA constructs containing HCV antigens have become one of the vaccine candidates for induction of anti-HCV cellular and humoral immunity. In this study, we constructed a novel expressing vector harboring a fusion sequence derived from an overlapping fragment in the middle of NS3 and a truncated core fragment to avoid troubles reported to be associated with full gene expression. Methods: The partial NS3 (pNS3) and core genes were amplified by RT-PCR method using serum of HCV infected patient harboring genotype 1a of virus. After purification and cloning the genes into TA-cloning vector, they were evaluated by sequencing and restriction digestion analysis. The resultant pNS3 and core gene subcloned into expression vector separately followed by expression evaluation using RT-PCR and western blotting. The core expressing vector exploited for amplification of a new truncated core (50-160aa) sequence using PCR. Truncated core fragment was first cloned into TA vector at a natural restriction site downstream of pNS3 fragment. The resulting fused sequence was cut and subcloned into expression vector. The integrity and ability of expression of this fused sequence was evaluated by sequencing followed by RT-PCR analysis after DNA transfection into 293 cells. Results: The repeated sequencing data showed sequence integrity among the gene fragments as well as homology among them and reference 1a sequences. The colony-PCR, RT-PCR and western blotting confirmed insertion of genes into expressing vector, expression of genes in 293 cell line and production of protein in 293 respectively. Conclusion: This new expressing vector harboring a novel fused fragments of NS3 and core genes may overcome shortcomings in vaccine design in the setting of HCV disease.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Construction of an Expression Vector Containing a Novel Fusion Sequence from Middle Region of NS3 and Truncated Core Genes of Hepatitis C Virus

et al. 2010

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“…High expression levels of the HCV C would not induce stronger immune responses but would instead inhibit the priming of immune responses, as shown in the previous studies [29], [44]. The interference of the HCV C with the priming of immune responses to other antigens may reduce the efficacy of combined genetic vaccines.…”

Section: Discussionmentioning

confidence: 81%

“…Earlier studies using a full-length HCV core DNA sequence have revealed a limited immunogenicity of the naked DNA [28], as increasing doses or repeated administration of the full-length HCV core DNA were unable to enhance the specific immune responses [29]. Interestingly, a vector expressing a truncated version of the HCV C improved the induction of specific T- and B-cell responses to the HCV C [28], [29], [30].…”

Section: Introductionmentioning

confidence: 99%

Inhibition of the HCV Core Protein on the Immune Response to HBV Surface Antigen and on HBV Gene Expression and Replication In Vivo

Zhu

Deng

et al. 2012

PLoS ONE

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The hepatitis C virus (HCV) core protein is a multifunctional protein that can interfere with the induction of an immune response. It has been reported that the HCV core protein inhibits HBV replication in vitro. In this study, we test the effect of the HCV core gene on the priming of the immune response to hepatitis B surface antigen (HBsAg) and on the replication of HBV in vivo. Our results showed that the full-length HCV core gene inhibits the induction of an immune response to the heterogeneous antigen, HBsAg, at the site of inoculation when HCV core (pC191) and HBsAg (pHBsAg) expression plasmids are co-administered as DNA vaccines into BALB/c mice. The observed interference effect of the HCV core occurs in the priming stage and is limited to the DNA form of the HBsAg antigen, but not to the protein form. The HCV core reduces the protective effect of the HBsAg when the HBsAg and the HCV core are co-administered as vaccines in an HBV hydrodynamic mouse model because the HCV core induces immune tolerance to the heterogeneous HBsAg DNA antigen. These results suggest that HCV core may play an important role in viral persistence by the attenuation of host immune responses to different antigens. We further tested whether the HCV core interfered with the priming of the immune response in hepatocytes via the hydrodynamic co-injection of an HBV replication-competent plasmid and an HCV core plasmid. The HCV core inhibited HBV replication and antigen expression in both BALB/c (H-2d) and C57BL/6 (H-2b) mice, the mouse models of acute and chronic hepatitis B virus infections. Thus, the HCV core inhibits the induction of a specific immune response to an HBsAg DNA vaccine. However, HCV C also interferes with HBV gene expression and replication in vivo, as observed in patients with coinfection.

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“…Several epitopes specific for T cells were also present in the amino acid region 100–150 of HCV core protein . However, this region has been involved in the deregulation of the immune system and it is toxic for bacteria ; therefore, this region was not included in Eq1 protein.…”

Section: Discussionmentioning

confidence: 99%

A chimeric protein encompassing hepatitis C virus epitopes is able to elicit both humoral and cell‐mediated immune responses in mice

Aguilar-Noriega

Alvarez‐Lajonchere

Brown

et al. 2014

Biotech and App Biochem

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Hepatitis C virus (HCV) infection is a worldwide health problem. Vaccines against this pathogen are not available and advances in this field are limited because of the high genetic variability of the virus, inaccessibility of animal models, and incomplete definition of immunological correlates of protection. In the present work, a chimeric protein, Eq1, encompassing HCV amino acid regions from structural antigens, was generated. Eq1 was expressed in GC-366 bacterial cells. After cell disruption, Eq1 was purified from the insoluble fraction by sequential steps of differential solubilization and metal chelating affinity chromatography. Eq1 was specifically recognized by anti-HCV positive human sera. Moreover, immunization of BALB/c mice with different doses of Eq1 formulated either in Alum or Freund's incomplete adjuvant elicited both humoral- and cellular-specific immune responses. Doses of 20 µg of Eq1 induced the strongest cell-mediated immune responses and only the formulation of this dose in Alum elicited a neutralizing antibody response against heterologous cell culture HCV. All these data together indicate that Eq1 is immunogenic in mice and might be an interesting component of vaccine candidates against HCV infection.

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The Wild-Type Hepatitis C Virus Core Inhibits Initiation of Antigen-Specific T- and B-Cell Immune Responses in BALB/c Mice

Cited by 17 publications

References 53 publications

Construction of an Expression Vector Containing a Novel Fusion Sequence from Middle Region of NS3 and Truncated Core Genes of Hepatitis C Virus

Construction of an Expression Vector Containing a Novel Fusion Sequence from Middle Region of NS3 and Truncated Core Genes of Hepatitis C Virus

Inhibition of the HCV Core Protein on the Immune Response to HBV Surface Antigen and on HBV Gene Expression and Replication In Vivo

A chimeric protein encompassing hepatitis C virus epitopes is able to elicit both humoral and cell‐mediated immune responses in mice

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