HCV core protein-expressing DNA vaccine induces a strong class I-binding peptide DTH response in mice.
The hepatitis C virus (HCV) core protein-encoding sequence (HCcAg) is the most conserved gene in HCV genome and therefore may be useful to study broadly reacting T-cell epitopes. In this study BALB/c and C57BL/6 mice were immunized with a DNA based vaccine expressing the first 176 aa of HCcAg (pIDKCo). After i.m or i.p injection of pIDKCo in BALB/c mice, a detectable INF-gamma secreting response to the relevant class I-binding peptide DLMGYIPLVGA (P1) (aa 132-142) was detected suggesting the induction of HCcAg specific CD8(+) T-cell effectors. CD8(+) T-cell responses were also monitored in vivo by T-cell-mediated DTH reactions after subcutaneous injection of class I-binding viral peptide P1. pIDKCo induced a strong P1-specific DTH response in both i.m and i.p immunized mice. To evaluate the T-cell response induced by pIDKCo in C57BL/6 mice, an HCcAg epitope was predicted based upon it containing the H-2K(b) binding motif XXXXF/YXXL (DLMGYIPL (P2)). pIDKCo induced a strong P2-specific DTH response with similar kinetics of swelling response to that observed in BALB/c mice. Previously, it had been demonstrated that only activated and protective CD8(+) effector T cells could mediate a specific DTH in footpads of virally infected mice after local injection of viral class I-binding peptides. Hence, pIDKCo could prime a strong HCcAg-specific T-cell response in mice with the potential capacity to exert their specific effector functions in peripheral tissues.
Acosta-Rivero
Nelson
N
Division of Vaccines, Center for Genetic Engineering and Biotechnology, P.O. Box 6162, C.P. 10600, Havana, Cuba. nelson.acosta@cigb.edu.cu
Dueñas-Carrera
Santiago
S
Alvarez-Lajonchere
Liz
L
Morales-Grillo
Juan
J
D000595:Amino Acid Sequence; D000818:Animals; D003601:Cytotoxicity Tests, Immunologic / Q000379:methods; D004487:Edema / Q000139:chemically induced / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005822:Genetic Vectors / Q000235:genetics; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology*; D007279:Injections, Subcutaneous; D007371:Interferon-gamma / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010446:Peptide Fragments / Q000276:immunology*; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology*; D014758:Viral Core Proteins / Q000235:genetics / Q000276:immunology*
D018984:Epitopes, T-Lymphocyte; D015395:Histocompatibility Antigens Class I; D010446:Peptide Fragments; D011994:Recombinant Proteins; D019444:Vaccines, DNA; D014758:Viral Core Proteins; C069130:nucleocapsid protein, Hepatitis C virus; D007371:Interferon-gamma