GI-5005, a yeast vector vaccine expressing an NS3-core fusion protein for chronic HCV infection.

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.