Efficient induction of T helper 1 CD4(+) T-cell responses to hepatitis C virus core and E2 by a DNA prime-adenovirus boost

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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.
Publisher
ELSEVIER SCI LTD
Issue Date
2003-11
Language
English
Article Type
Article
Keywords

RECOMBINANT ADENOVIRUSES; LYMPHOCYTE RESPONSES; PLASMID DNA; INFECTION; PROTEINS; VACCINE; IMMUNIZATION; MECHANISM; MICE

Citation

VACCINE, v.21, no.31, pp.4555 - 4564

ISSN
0264-410X
DOI
10.1016/S0264-410X(03)00499-7
URI
http://hdl.handle.net/10203/201434
Appears in Collection
MSE-Journal Papers(저널논문)
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