Whole recombinant yeast-based immunotherapy induces potent T cell responses targeting HCV NS3 and Core proteins.

Abstract

Control of primary infection with hepatitis C virus (HCV) is associated with robust and broad T cell immunity. In contrast, chronic infection is characterized by weak T cell responses suggesting that an approach that boosts these responses could be a therapeutic advance. Saccharomyces cerevisiae is an effective inducer of innate and adaptive cellular immunity and we have generated recombinant yeast cells (GI-5005) that produce an HCV NS3-Core fusion protein. Pre-clinical studies in mice showed that GI-5005 induced potent antigen-specific proliferative and cytotoxic T cell responses that were associated with Th1-type cytokine secretion. In studies in which GI-5005 was administered up to 13 times, no detectable vector neutralization or induction of tolerance was observed. Prophylactic as well as therapeutic administration of GI-5005 in mice led to eradication of tumor cells expressing HCV NS3 protein. Immunotherapy with GI-5005 is being evaluated in chronic HCV infected individuals in a Phase 1 clinical trial.

• Authors: Aurelia A Haller, Georg M Lauer, Thomas H King, Charles Kemmler, Valerie Fiolkoski, Yingnian Lu, Don Bellgrau, Timothy C Rodell, David Apelian, Alex Franzusoff, Richard C Duke
• Journal: Vaccine (Vaccine) Vol. 25 Issue 8 Pg. 1452-63 (Feb 09 2007) ISSN: 0264-410X [Print] Netherlands
• PMID: 17098335 (Publication Type: Journal Article)

Chemical References

• Cytokines
• NS3 protein, hepatitis C virus
• Recombinant Fusion Proteins
• Viral Core Proteins
• Viral Hepatitis Vaccines
• Viral Nonstructural Proteins
• nucleocapsid protein, Hepatitis C virus

Topics

• Animals
• Cell Line, Tumor
• Cytokines (immunology, metabolism)
• HeLa Cells
• Hepacivirus (genetics, immunology)
• Hepatitis C (immunology, prevention & control)
• Humans
• Immunotherapy (methods)
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Recombinant Fusion Proteins (genetics, immunology)
• Saccharomyces cerevisiae (genetics, immunology, metabolism)
• T-Lymphocytes, Cytotoxic (immunology)
• T-Lymphocytes, Helper-Inducer (immunology)
• Viral Core Proteins (biosynthesis, genetics, immunology)
• Viral Hepatitis Vaccines (genetics, immunology)
• Viral Nonstructural Proteins (biosynthesis, genetics, immunology)