Vaccine 2004 Apr 16;2213-14:1656-65. doi: 10.1016/j.vaccine.2003.09.047.

Immunization with hepatitis C virus core gene triggers potent T-cell response, but affects CD4+ T-cells.

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Numerous attempts to induce immunity against HCV core (HCV-C) by DNA immunization met serious difficulties in optimizing T-helper cell and antibody responses. Immunomodulatory properties of HCV-C could be blamed that seem to be dependent on the genotype of HCV source. Here, we characterized HCV-C gene from HCV 1b isolate 274933RU. Eukaryotic expression of HCV-C was effectively driven by CMVIE, while human elongation factor 1 alpha promoter directed low levels of HCV-C expression. C57BL/6 mice were immunized with CMVIE-driven HCV-C gene, and assessed for specific antibody production, T-cell proliferation and cytokine secretion. The number and proportion of CD19+, CD3+, CD3+/CD4+, and CD3+/CD8+ splenocytes in HCV-C gene recipients was evaluated by flow cytometry. A significant mounting drop in CD3+/CD4+ T-cell counts occurred in HCV-C gene-recipients as compared to the controls. Despite that, 75% of mice exhibited core-specific cellular reactivity revealed as high proliferative responses to HCV-C and HCV-C peptides. Stimulated T-cells secreted predominantly IFN-gamma and IL-2. A shift of epitope specificity was observed with the early response being broad, and the late limited to the HCV-C C-terminus. Thus, we demonstrate both T-cell immunogenicity and T-cell modulation by core of HCV 1b. Immune modulation by HCV core may affect host ability to mount long-lasting cellular and antibody response and should be dealt with in designing core-based HCV vaccines.

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