Efficient induction of T helper 1 CD4+ T-cell responses to hepatitis C virus core and E2 by a DNA prime-adenovirus boost.
Hepatitis C virus (HCV) is an important causative agent of liver disease, but currently there is no available prophylactic vaccine against HCV infection. Here, we investigated the HCV E2- and core-specific T-cell responses induced by DNA (D) and/or recombinant adenovirus (A) vaccines. In single (D versus A) or double immunizations (D-D versus A-A), the recombinant adenovirus vaccines induced higher levels of IFN-gamma secreting T-cell response and cytotoxic T lymphocytes (CTL) response than the DNA vaccines. However, a heterologous (D-A) regimen elicited the highest level of T helper 1 (Th1) CD4(+) T-cell responses. Furthermore, three E2-specific CTL epitopes were mapped using a peptide pool spanning the E2 protein sequence (a.a. 384-713) in BALB/c mice, and one of these (E2 405-414: SGPSQKIQLV) was shown to be immunodominant. Interestingly, no significant differences were found in the repertoire of E2-specific T-cell responses or in the immunodominance hierarchy of the three epitopes induced by D-D, D-A, A-A, and A-D, indicating that the breadth and hierarchy of T-cell responses is independent of these different vaccination regimens. In conclusion, the heterologous DNA prime-recombinant adenovirus boost regimen described offers an efficient promising strategy for the development of an effective T-cell-based HCV vaccine.
National Research Laboratory of DNA Medicine, Division of Molecular and Life Science, Pohang University of Science and Technology, San 31, Hyoja-dong, Nam-gu, Pohang, Kyungbuk 790-784, South Korea.
Su-Hyung
SH
Park
Se-Hwan
SH
Yang
Chang Geun
CG
Lee
Jin-Won
JW
Youn
Jun
J
Chang
Young Chul
YC
Sung
D000256:Adenoviridae / Q000276:immunology*; D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002469:Cell Separation; D002860:Chromium Radioisotopes; D000939:Epitopes; D005260:Female; D016174:Hepacivirus / Q000276:immunology*; D007117:Immunization, Secondary; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology; D010957:Plasmids / Q000235:genetics; D019444:Vaccines, DNA / Q000276:immunology; D014759:Viral Envelope Proteins / Q000276:immunology*; D014765:Viral Vaccines / Q000276:immunology*; D014779:Virus Replication / Q000235:genetics
D002860:Chromium Radioisotopes; D000939:Epitopes; D010455:Peptides; D019444:Vaccines, DNA; D014759:Viral Envelope Proteins; D014765:Viral Vaccines