A polyantigenic genotype 1a/1b consensus hepatitis C virus DNA vaccine induces broadly reactive HCV-specific cellular immune responses in both mice and non-human primates (VAC7P.985)

Abstract

Abstract Chronic HCV is a surreptitious disease that can lead to cirrhosis and cancer decades following infection. Each year, 3-4 million individuals are infected. However, there are currently no vaccines available to prevent chronic HCV infection. From patients who acutely resolve (A.R.) infection, a strong and broadly reactive cytotoxic T lymphocyte (CTL) response is associated with viral clearance. With in vivo electroporation (E.P.), DNA vaccines induce strong CTL responses, making them well suited for an HCV vaccine. Our vaccine strategy maximizes recipients' opportunity to induce a broad T cell response with genotype 1a/1b consensus sequences of multiple HCV antigens. Immunogenicity of the HCV vaccine was assessed in mice and non-human primates (NHP). Animals were immunized three times, two weeks apart for mice and six weeks apart for NHP as an intramuscular injection followed by E.P. In mice, interferon-γ (IFNγ) responses spanned all HCV antigens and with total values exceeding 6,000 spot-forming units per million mononuclear cells (SFU) within both the spleen and liver by IFNγ ELIspot. Similarly in NHP, immune responses up to 4,680 SFU per million PBMCs were detectable by IFNγ ELISpot. Flow cytometry revealed HCV-specific CD4+ and CD8+ T cell responses by cytokine staining and significant frequencies of cytolytic CTL compared to baseline. Here, we have demonstrated the magnitude and breadth of HCV-specific immune responses elicited by an HCV DNA vaccine in mice and NHP.