Vaccination with protein-transduced dendritic cells elicits a sustained response to hepatitis C viral antigens.
BACKGROUND & AIMS: Professional antigen-presenting dendritic cells are capable of eliciting a vigorous antiviral response in naive T cells. The administration of antigen-loaded dendritic cells offers a potential approach to induce high-level immunity against hepatitis C virus. METHODS: The dendritic cell population in mice was expanded in vivo by hydrodynamic delivery of naked DNA that encoded the secreted form of human fms-like tyrosine kinase 3 ligand. The CD11c-enriched dendritic cell population obtained from the spleen was transduced in vitro with recombinant hepatitis C virus core and nonstructural 5 proteins by using macromolecular-based protein delivery. Vaccine efficacy was assessed with a cytotoxic T-lymphocyte assay, cytokine enzyme-linked immunosorbent assays, and intracellular cytokine staining in vitro and by a tumor challenge model in vivo. RESULTS: Relative to mice inoculated with nontransduced dendritic cells, splenocytes derived from mice immunized with either hepatitis C virus core-transduced or nonstructural 5-transduced dendritic cells showed 3- to 5-fold greater antigen-specific cytotoxic T lymphocyte activity. The CD4(+) T cells obtained from mice immunized with nonstructural 5-transduced dendritic cells produced interferon gamma, but not interleukin 4, when stimulated with nonstructural 5. In contrast, T cells derived from mice immunized with hepatitis C virus core-transduced dendritic cells produced neither interferon gamma nor interleukin 4 when stimulated with core protein. Mice vaccinated with nonstructural 5-transduced dendritic cells, but not a nonstructural 5-expressing plasmid, showed a sustained antiviral response to nonstructural 5 as evidenced by reduced growth of nonstructural 5-expressing tumor cells inoculated 10 weeks after vaccination. CONCLUSIONS: These findings suggest that vaccination with protein-transduced dendritic cells may constitute an important antiviral strategy for hepatitis C virus.[1]References
- Vaccination with protein-transduced dendritic cells elicits a sustained response to hepatitis C viral antigens. Kuzushita, N., Gregory, S.H., Monti, N.A., Carlson, R., Gehring, S., Wands, J.R. Gastroenterology (2006) [Pubmed]
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