Prophylactic DNA vaccine for hepatitis C virus (HCV) infection: HCV-specific cytotoxic T lymphocyte induction and protection from HCV-recombinant vaccinia infection in an HLA-A2.1 transgenic mouse model

DNA vaccines express antigens intracellularly and effectively induce cellul ar immune responses. Because only chimpanzees can be used to model human he patitis C virus (HCV) infections, we developed a small-animal model using H LA-A2.1-transgenic mice to test induction of HLA-A2.1-restricted cytotoxic T lymphocytes (CTLs) and protection against recombinant vaccinia expressing HCV-core, A plasmid encoding the HCV-core antigen induced CD8(+) CTLs spec ific for three conserved endogenously expressed core peptides presented by human HLA-A2.1, When challenged, DNA-immunized mice showed a substantial (5 -12 log(10)) reduction in vaccinia virus titer compared with mock-immunized controls. This protection, lasting at least 14 mo, was shown to be mediate d by CD8+ cells. Thus, a DNA vaccine expressing HCV-core is a potential can didate for a prophylactic vaccine for HLA-A2.1(+) humans.