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-γ 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.
Bibliographical noteFunding Information:
We express our thanks to Sang Chun Lee for animal management. This work was supported by a grant (3II0200101) from a consortium project (Genexine Co. Ltd., Daewoong Pharm. Co. Ltd., Dong-A Pharm. Co. Ltd., POSCO), a grant of the Korea Health 21 R&D Project, Ministry of Health & Welfare, Republic of Korea (02-PJ2-PG1-CH16-0002), a grant of National Research Lab Program of the National S&T Program from Ministry of S&T (M1-0001-00-0089 and M10204000060-02J0000-05510), and a grant No. 1999-2-212-004-5 from the Basic Research Program of the Korea Science & Engineering Foundation.
- DNA prime-recombinant adenovirus boost
- Hepatitis C virus
- Th1 CD4 T-cell response