Genetic immunization generates broad-based cellular and humoral immune responses against the non-structural proteins of hepatitis C virus

Encke, Jens; Putlitz, Jasper zu; Geißler, Michael; Wands, Jack R.

doi:10.1016/s0016-5085(98)85023-3

Cited by 18 publications

(27 citation statements)

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“…Peptides were proposed by computer simulation (University of Wisconsin Genetics Computer Group (UWGCG), peptide structure program) and prepared by EMC microcollections (Tübingen, Germany) with the following sequences: YQVRNSSGLYHVTNDCPNSS (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20), PGCVPCVREGNAS RCWVAVT (33-53), REGNASRCWVAVTPTVATRDGKL and PRRHWTTQDCNCSIYPG (104-120). Establishment and characterization of the stable transfected cell line expressing HCV core protein (SP2-19) and the control cell line SP2-0 have been described previously [34].…”

Section: Antigens and Cell Linesmentioning

confidence: 99%

“…induction of only borderline immunity after DNAimmunization or safety issues with viral vectors [15,16]. A number of different vaccine approaches have been investigated against HCV infection in the past like DNA vaccination [17][18][19], vaccination with recombinant proteins or peptides [11], vaccines based on virus-like particles [20] and viral or other pathogen vectors containing genetic information of HCV proteins [21].…”

Section: Introductionmentioning

confidence: 99%

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Prophylactic and therapeutic vaccination with dendritic cells against hepatitis C virus infection

Encke

Findeklee²,

Geib³

et al. 2005

Clinical and Experimental Immunology

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Section: Antigens and Cell Linesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Prophylactic and therapeutic vaccination with dendritic cells against hepatitis C virus infection

Encke

Findeklee²,

Geib³

et al. 2005

Clinical and Experimental Immunology

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“…In this regard, we have provided evidence by use of a murine model of chronic ethanol feeding that CD4 ϩ T-cell proliferation and cytotoxic T-lymphocyte (CTL) responses generated by genetic immunization against hepatitis C virus (HCV) core and nonstructural 5 (NS5) proteins were substantially reduced compared to those in isocaloric pair control mice (6,9,10). Further investigation revealed that CTL activity could be restored partly with additions of IL-2 and fully by coimmunization with granulocyte-macrophage colony-stimulating factor (GM-CSF) expression plasmids, suggesting that antigen-presenting cells (APCs) may be a critical target of ethanol's action to promote impaired CD4 ϩ and CD8 ϩ T-cell priming (6,9,10,33).…”

mentioning

confidence: 99%

“…Further investigation revealed that CTL activity could be restored partly with additions of IL-2 and fully by coimmunization with granulocyte-macrophage colony-stimulating factor (GM-CSF) expression plasmids, suggesting that antigen-presenting cells (APCs) may be a critical target of ethanol's action to promote impaired CD4 ϩ and CD8 ϩ T-cell priming (6,9,10,33). Indeed, subsequent studies revealed that adoptive transfer of splenic DCs derived from control but not ethanol-fed mice restored the generation of virus-specific CTL activity in the chronically ethanol-fed animals (1).…”

mentioning

confidence: 99%

Ethanol Inhibits Antigen Presentation by Dendritic Cells

Eken

Ortiz

Wands

2011

Clin. Vaccine Immunol.

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Previous studies suggest that altered virus-specific T-cell responses observed during chronic ethanol exposure may be due to abnormal functioning of dendritic cells (DCs). Here we explored the effects of ethanol on exogenous antigen presentation by DCs. BALB/c, C57BL/6, and CBA/caj mice were fed ethanol or an isocaloric control diet for 8 weeks. The splenic DC population was expanded using an Flt3L expression plasmid via tail vein injection. DCs were purified and assessed for antigen presentation and processing and for peptide-major histocompatibility complex class I and II (MHCI and MHCII) formation on the cell surface. Interleukin-2 (IL-2) was measured as an indicator of antigen-specific T-cell activation by DCs in coculture. Antigen processing and peptide-MHCII complexes were evaluated by flow cytometry. We observed that ethanol not only suppressed allogeneic peptide presentation to T cells by DCs but also altered presentation of exogenous ovalbumin (OVA) peptide 323-339 to an OVA-specific DO11 T-cell line as well as to OVA-sensitized primary T cells. Smaller amounts of peptide-MHCII complexes were found on the DCs isolated from the spleens of ethanol-fed mice. In contrast to MHCII presentation, cross-presentation of exogenous OVA peptide via MHCI by DCs remained intact. More importantly, ethanol-exposed DCs had reduced B7-DC and enhanced ICOS-L (inhibitory) costimulatory molecule expression. Ethanol inhibits exogenous and allogeneic antigen presentation and affects the formation of peptide-MHCII complexes, as well as altering costimulatory molecule expression on the cell surface. Therefore, DC presentation of peptides in a favorable costimulatory protein environment is required to subsequently activate T cells and appears to be a critical target for the immunosuppressive effects of ethanol.

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“…We (using pnewCMVII-NS5a), 28 and others, [29][30][31] have reported that intramuscular (IM) injection of ''naked'' plasmid DNA can elicit HCV-specific cellular immune responses in mice. However, T-cell-mediated immune responses primed by expressing antigens in the muscle of mice might differ from those primed when antigens are expressed primarily in the liver, as is thought to occur during HCV infection.…”

mentioning

confidence: 99%

Priming of hepatitis C virus-specific cytotoxic t lymphocytes in mice following portal vein injection of a liver-specific plasmid DNA

Lee¹,

Manning²,

Arian³

et al. 2000

Hepatology

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The immunology of hepatitis C virus (HCV) infection should be studied in the context of HCV antigen expression in the liver, because HCV primarily infects this organ. Indeed, the nature, function, and fate of T cells primed after antigen expression in the liver might differ from those primed when antigens are expressed systemically or in other organs, because the nature of the antigen-presenting cells (APCs) involved may be different. In addition, the normal liver contains a resident population of lymphocytes that differ from those present at other sites. Thus, we investigated whether HCV-specific CD8 ؉ cytotoxic T cells (CTLs) could be elicited following portal vein (PV) injection of plasmid DNA in mice whose hepatic veins were transiently occluded. We show that PV injection of mice with ''naked'' DNA expressing the HCV-NS5a protein, under the control of a liver-specific enhancer/promoter, resulted in NS5a expression in the liver and the priming of HCVspecific CTLs. These results suggested that such a model might be relevant to the study of HCV-specific immune responses primed during natural infection. (HEPATOLOGY 2000;31:1327-1333.)Hepatitis C virus (HCV), a positive-strand RNA virus member of the Flaviviridae family, 1 is recognized as a major public health concern. In addition to being one of the leading causes of chronic liver disease, 2 chronic HCV infection has been associated with autoimmune syndromes, immune complex disorders, and mixed cryoglobulinemia. 3,4 One of the most striking features of HCV is that it seems able, in most instances, to circumvent eradication by the immune system. It is estimated that up to 75% of patients infected with HCV become chronically infected, 2,5-7 despite the fact that most patients generate HCV-specific antibody, [8][9][10][11][12] as well as CD4 ϩ and CD8 ϩ T-cell responses. [13][14][15][16] On the other hand, there is evidence that humoral and T-cell-mediated immune responses to HCV infection can, at least in some instances, determine the outcome of HCV infection and disease. [17][18][19][20] In spite of recent progress in the management of chronic HCV disease, the current therapies for chronic HCV infection often do not result in viral clearance. 21,22 Thus, there is a growing interest in developing immune-based therapies for HCV. To develop such therapies, one must understand the immune responses to HCV infection, because they should provide insight into the mechanisms involved in limiting HCV replication in infected hosts. Despite the fact that substantial efforts have been made to decipher the immunology of HCV infection, it remains poorly understood. The main factors responsible for the relatively slow progress in this field are the unavailability of a small animal model for infection and disease, and inefficient systems for cultivating the virus. Because acute hepatitis in humans has been difficult to study, most attempts aimed at clarifying the immune responses to HCV have been conducted in patients with chronic hepatitis or in chimpanzees, the only reliable a...

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Genetic immunization generates broad-based cellular and humoral immune responses against the non-structural proteins of hepatitis C virus

Cited by 18 publications

References 0 publications

Prophylactic and therapeutic vaccination with dendritic cells against hepatitis C virus infection

Prophylactic and therapeutic vaccination with dendritic cells against hepatitis C virus infection

Ethanol Inhibits Antigen Presentation by Dendritic Cells

Priming of hepatitis C virus-specific cytotoxic t lymphocytes in mice following portal vein injection of a liver-specific plasmid DNA

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