Immunization with hepatitis C virus core gene triggers potent T-cell response, but affects CD4+ T-cells.
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.
Isaguliants
Maria G
MG
Ivanovsky Institute of Virology, 123 098 Moscow, Russia. maria.isaguliants@smi.ki.se
Petrakova
Natalia V
NV
Kashuba
Elena V
EV
Suzdaltzeva
Yulia G
YG
Belikov
Sergey V
SV
Mokhonov
Vladislav V
VV
Prilipov
Alexei G
AG
Matskova
Ludmila
L
Smirnova
Irina S
IS
Jolivet-Reynaud
Colette
C
Nordenfelt
Erik
E
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
D007074:Immunoglobulin G; D014758:Viral Core Proteins; D014764:Viral Proteins; D014765:Viral Vaccines; C069130:nucleocapsid protein, Hepatitis C virus