title: Immunization with hepatitis C virus core gene triggers potent T-cell response, but affects CD4+ T-cells.
abstract: 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.
authors.affiliation: Ivanovsky Institute of Virology, 123 098 Moscow, Russia. maria.isaguliants@smi.ki.se
authors.forename: Maria G
authors.initials: MG
authors.lastname: Isaguliants
authors.forename: Natalia V
authors.initials: NV
authors.lastname: Petrakova
authors.forename: Elena V
authors.initials: EV
authors.lastname: Kashuba
authors.forename: Yulia G
authors.initials: YG
authors.lastname: Suzdaltzeva
authors.forename: Sergey V
authors.initials: SV
authors.lastname: Belikov
authors.forename: Vladislav V
authors.initials: VV
authors.lastname: Mokhonov
authors.forename: Alexei G
authors.initials: AG
authors.lastname: Prilipov
authors.forename: Ludmila
authors.initials: L
authors.lastname: Matskova
authors.forename: Irina S
authors.initials: IS
authors.lastname: Smirnova
authors.forename: Colette
authors.initials: C
authors.lastname: Jolivet-Reynaud
authors.forename: Erik
authors.initials: E
authors.lastname: Nordenfelt
mesh_terms: D016475:3T3 Cells; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D005434:Flow Cytometry; D006526:Hepatitis C / Q000276:immunology*; D007114:Immunization; D007074:Immunoglobulin G / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D009865:Oocytes; D010957:Plasmids / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014758:Viral Core Proteins / Q000276:immunology*; D014764:Viral Proteins / Q000276:immunology; D014765:Viral Vaccines / Q000276:immunology*; D014982:Xenopus laevis
chemical_list: D007074:Immunoglobulin G; D014758:Viral Core Proteins; D014764:Viral Proteins; D014765:Viral Vaccines; C069130:nucleocapsid protein, Hepatitis C virus