Development of a hepatitis C virus vaccine

Inchauspé, Geneviève; Feinstone, Stephen M.

doi:10.1016/s1089-3261(02)00067-3

Cited by 31 publications

(20 citation statements)

References 58 publications

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“…No effective vaccine is available, and the consensus therapeutic treatment, consisting of PEGylated alpha interferon (IFN-␣) in combination with ribavirin, is poorly effective against some viral genotypes (16,30).…”

Section: Success In Resolving Hepatitis C Virus (Hcv) Infection Has Bmentioning

confidence: 99%

“…The current literature suggests that once chronic infection is established, the HCV-specific immune response exerts some control over viral load, but in most cases it is unable to terminate persistent infection and to resolve chronic hepatitis (16). As in the case of other pathogens, like human immunodeficiency virus type 1 (HIV-1), that are able to establish persistent infection, the outcome of HCV disease is the result of a balance between the kinetics and the magnitude of the immune response, the pathogen replication rate, and the accessibility of infected cells to the immune response.…”

Section: Success In Resolving Hepatitis C Virus (Hcv) Infection Has Bmentioning

confidence: 99%

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A Novel Adenovirus Type 6 (Ad6)-Based Hepatitis C Virus Vector That Overcomes Preexisting Anti-Ad5 Immunity and Induces Potent and Broad Cellular Immune Responses in Rhesus Macaques

Capone

Meola

Ercole

et al. 2006

J Virol

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Success in resolving hepatitis C virus (HCV) infection has been correlated to vigorous, multispecific, and sustained CD8؉ T-cell response in humans and chimpanzees. The efficacy of inducing T-cell-mediated immunity by recombinant serotype 5 adenovirus vector has been proven in many animal models of infectious diseases, but its immunogenicity can be negatively influenced by preexisting immunity against the vector itself. To evaluate the less prevalent adenovirus serotype 6 (Ad6) as an alternative vector for and HCV vaccine development, we have generated serotype 5 and 6 adenoviral vectors directing expression of the nonstructural region of HCV (MRKAd5-NSmut and MRKAd6-NSmut). Immunogenicity studies in mice showed that the two vectors induced comparable T-cell responses but that only MRKAd6-NSmut was not suppressed in the presence of anti-Ad5 immunity. In contrast, preexisting anti-Ad5 immunity dramatically blunted the immunogenicity of the serotype 5-based HCV vector. Furthermore, MRKAd6-NSmut showed equivalent potency, breadth, and longevity of HCV-specific T-cell responses in rhesus macaques as the corresponding Ad5-based vector over a wide range of doses and was capable of boosting DNA-primed animals even if administered at low doses. These data support the use of the MRKAd6-NSmut for anti-HCV immunotherapy and, more generally, for the Ad6 serotype as a better genetic vaccine vehicle than Ad5.

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Section: Success In Resolving Hepatitis C Virus (Hcv) Infection Has Bmentioning

confidence: 99%

Section: Success In Resolving Hepatitis C Virus (Hcv) Infection Has Bmentioning

confidence: 99%

A Novel Adenovirus Type 6 (Ad6)-Based Hepatitis C Virus Vector That Overcomes Preexisting Anti-Ad5 Immunity and Induces Potent and Broad Cellular Immune Responses in Rhesus Macaques

Capone

Meola

Ercole

et al. 2006

J Virol

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“…DNA immunization has also yielded disappointing results in some models (23). It seems that DNA alone may not be an efficient immunogen for the induction of humoral immune responses (43).…”

Section: Introductionmentioning

confidence: 99%

Comparison of Antibody- and Cell-Mediated Immune Responses After Intramuscular Hepatitis C Immunizations of BALB/c Mice

et al. 2005

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Current treatments for hepatitis C infection have limited efficacy, and there is no vaccine available. The goal of this study was to compare the immune response to several immunization combinations against hepatitis C virus (HCV). Six groups of mice were immunized at weeks 0, 4, and 8 with different combinations of a candidate HCV vaccine consisting of 100 microg recombinant HCV core/E1/E2 (rHCV) DNA plasmid and/or 25 microg rHCV polyprotein and 50 microL Montanide ISA- 51. Four weeks after the last injection, all groups of mice were sacrificed and blood samples and spleens were collected for measuring the levels of specific HCV antibodies (total IgG, IgG1, and IgG2a). Cell proliferation and intracellular interferon-gamma were also measured. Among the groups of immunized mice, only the mice immunized with rHCV DNA plasmid, rHCV polyprotein, and montanide (group D) and mice immunized with rHCV polyprotein and montanide (group F) demonstrated a significant increase in the total IgG titer after immunization. IgG1 was the predominant antibody detected in both groups D and F. No IgG2a was detected in any of the groups. Proliferation assays demonstrated that splenocytes from group D and group C (rHCV DNA primed/rHCV polyprotein boost) developed significant anti-HCV proliferative responses. The combination of an rHCV DNA plasmid, rHCV polyprotein, and montanide induced a high antibody titer with a predominance of IgG1 antibodies and recognized the major neutralization epitopes in HVR1. In contrast, group C did not show an increase in anti-HCV antibodies, but did show a proliferative response.

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“…The majority of HCV-infected individuals develop chronic hepatitis that may progress to liver cirrhosis and hepatocellular carcinoma (15). Treatment options for chronic HCV infection are limited, and a vaccine to prevent HCV infection is not available (11,15,17).HCV has been classified in a separate genus (Hepacivirus) of the Flaviviridae family. The virion contains a positive-stranded RNA genome of approximately 9.6 kb in length (25).…”

mentioning

confidence: 99%

Scavenger Receptor Class B Type I and Hepatitis C Virus Infection of Primary Tupaia Hepatocytes

Barth

Cerino²,

Arcuri³

et al. 2005

J Virol

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Hepatitis C virus (HCV) isHepatitis C virus (HCV) is a major cause of posttransfusion and community-acquired hepatitis in the world (8,24,25). The majority of HCV-infected individuals develop chronic hepatitis that may progress to liver cirrhosis and hepatocellular carcinoma (15). Treatment options for chronic HCV infection are limited, and a vaccine to prevent HCV infection is not available (11,15,17).HCV has been classified in a separate genus (Hepacivirus) of the Flaviviridae family. The virion contains a positive-stranded RNA genome of approximately 9.6 kb in length (25). The genome consists of a highly conserved 5Ј noncoding region followed by a long open reading frame of 9,030 to 9,099 nucleotides that is translated into a single polyprotein of 3,010 to 3,030 amino acids. Processing of the polyprotein occurs by a combination of host and viral proteases. The HCV structural proteins comprise the putative nucleocapsid or core protein and the two envelope glycoproteins E1 and E2 (25). The E2 glycoprotein is thought to be responsible for initiating virus attachment due to its ability to bind to human cells (32).HCV purified from plasma has been reported to exist in association with plasma lipoproteins, suggesting that the virus may use the low-density lipoprotein receptor for uptake (2). In the absence of highly purified native infectious HCV particles as a tool for the study of virus-cell interaction, recombinant HCV glycoprotein E2, E1E2 liposomes (22), infectious HCV pseudotype particles expressing E1 and E2 (HCVpp) (4, 16), and HCV-like particles (HCV-LPs) (3,39,41) have been used to analyze virus-cell membrane interaction. Based on these experimental in vitro studies, CD81 (5, 32), dendritic cellspecific intercellular adhesion molecule 3 grabbing nonintegrin (33) and highly sulfated heparan sulfate (3) have been proposed to play a role in mediating E2 binding and/or HCV internalization.Recently, the scavenger receptor class B type I (SR-BI) has been proposed as a putative HCV receptor candidate (36). SR-BI, a high-density lipoprotein-binding molecule, plays a functional role in lipid metabolism and is highly expressed in hepatocytes and steroidgenic tissues (34). SR-BI is a 509-residue glycoprotein with a large extracellular loop (LEL) anchored to the plasma membrane at both the N and C termini by transmembrane domains with short extensions into the cytoplasm (21). SR-BI has been shown to play a role in mediating the binding of recombinant E2 to HepG2 hepatoma cells and the entry of recombinant HCVpp into Huh-7 hepatoma cells (5, 36). Due to the lack of convenient in vitro or in vivo models for the study of HCV infection, the

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Development of a hepatitis C virus vaccine

Cited by 31 publications

References 58 publications

A Novel Adenovirus Type 6 (Ad6)-Based Hepatitis C Virus Vector That Overcomes Preexisting Anti-Ad5 Immunity and Induces Potent and Broad Cellular Immune Responses in Rhesus Macaques

A Novel Adenovirus Type 6 (Ad6)-Based Hepatitis C Virus Vector That Overcomes Preexisting Anti-Ad5 Immunity and Induces Potent and Broad Cellular Immune Responses in Rhesus Macaques

Comparison of Antibody- and Cell-Mediated Immune Responses After Intramuscular Hepatitis C Immunizations of BALB/c Mice

Scavenger Receptor Class B Type I and Hepatitis C Virus Infection of Primary Tupaia Hepatocytes

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