Induction of intrahepatic HCV NS4B, NS5A and NS5B-specific cellular immune responses following peripheral immunization.

Lang Kuhs KA, Toporovski R, Yan J, Ginsberg AA, Shedlock DJ, Weiner DB
PLoS One. 2012 7 (12): e52165

PMID: 23284919 · PMCID: PMC3528776 · DOI:10.1371/journal.pone.0052165

Numerous studies have suggested that an effective Hepatitis C Virus (HCV) vaccine must induce strong cytotoxic and IFN-γ+ T cell responses targeting the non-structural region of the virus. Most importantly, these responses must be able to migrate into and remain functional within the liver, an organ known to cause T cell tolerance. Using three novel HCV DNA vaccines encoding non-structural proteins NS4B, NS5A and NS5B, we assessed the ability of peripheral immunization to induce functional intrahepatic immunity both in the presence and absence of cognate HCV antigen expression within the liver. We have shown that these constructs induced potent HCV-specific CD4+ and CD8+ T cell responses in the spleen of C57BL/6 mice and that these responses were detected within the liver following peripheral immunization. Additionally, using a transfection method to express HCV antigen within the liver, we showed that intrahepatic HCV-specific T cells remained highly functional within the liver and retained the ability to become highly activated as evidenced by upregulation of IFN-γ and clearance of HCV protein expressing hepatocytes. Taken together, these findings suggest that peripheral immunization can induce potent HCV-specific T cell responses able to traffic to and function within the tolerant environment of the liver.

MeSH Terms (14)

Animals CD4-Positive T-Lymphocytes CD8-Positive T-Lymphocytes Cells, Cultured Female Flow Cytometry Fluorescent Antibody Technique Hepacivirus Immunity, Cellular Liver Mice Mice, Inbred C57BL Microscopy, Confocal Viral Nonstructural Proteins

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