title: GI-5005, a yeast vector vaccine expressing an NS3-core fusion protein for chronic HCV infection.
abstract: The HCV nonstructural protein 3 (NS3) and core protein are highly conserved among various HCV genotypes, and several B- and T-cell epitopes have been characterized with these antigens. The immunotherapeutic vaccine GI-5005, being developed by GlobeImmune Inc, is a Tarmogen (targeted molecular immunogen) consisting of recombinant Saccharomyces cerevisiae yeast expressing an HCV NS3-core fusion protein designed to elicit antigen-specific host CD4+ and CD8+ T-cell responses for the treatment of chronic HCV infection. GI-5005 has demonstrated robust immunogenicity in preclinical in vitro and in vivo models. In a phase Ib clinical trial, GI-5005 monotherapy was well tolerated and displayed efficacy in patients with chronic HCV infection. At the time of publication, interim data were available from a completed phase II trial that evaluated a triple therapy of GI-5005 in combination with the standard-of-care (SOC; PEGylated-IFNalpha and ribavirin) regimen, compared with the SOC regimen alone. Triple therapy resulted in improved early virological responses in all treatment-naïve patients. End-of-trial results, including data of sustained virological responses, are required to better evaluate the efficacy of GI-5005 for the improvement of viral clearance and to compare the efficacy of the agent with other approaches such as NS3 protease inhibitors.
authors: Hopitaux Universitaires de Strasbourg, Service d'Hepatogastroenterologie, Strasbourg, France.
authors: Francois
authors: F
authors: Habersetzer
authors: Thomas F
authors: TF
authors: Baumert
authors: Francoise
authors: F
authors: Stoll-Keller
mesh_terms: D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D000075202:Contraindications; D004353:Drug Evaluation, Preclinical; D005822:Genetic Vectors / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D010330:Patents as Topic; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D013329:Structure-Activity Relationship; D014614:Vaccines, Synthetic / Q000009:adverse effects / Q000627:therapeutic use*; D014760:Viral Fusion Proteins / Q000378:metabolism*; D017361:Viral Nonstructural Proteins / Q000378:metabolism*; D014765:Viral Vaccines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D000998:Antiviral Agents; D014614:Vaccines, Synthetic; D014760:Viral Fusion Proteins; D017361:Viral Nonstructural Proteins; D014765:Viral Vaccines; C544594:GI 5005; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases