Enhancement of immunoglobulin G2A and cytotoxic T-lymphocyte responses by a booster immunization with recombinant hepatitis C virus E2 protein in E2 DNA-primed mice

The induction of strong cytotoxic T-lymphocyte (CTL) and humoral responses appear to be essential for the elimination of persistently infecting viruse s, such as hepatitis C virus (HCV). Here, we tested several vaccine regimen s and demonstrate that a combined vaccine regimen, consisting of HCV E2 DNA priming and boosting with recombinant E2 protein, induces the strongest im mune responses to HCV E2 protein. This combined vaccine regimen augments E2 -specific immunoglobulin G2a (IgG2a) and CD8(+) CTL responses to a greater extent than immunizations with recombinant E2 protein and E2 DNA alone, res pectively. In addition, the data showed that a protein boost following one DNA priming was also effective, but much less so than those following two D NA primings, These data indicate that sufficient DNA priming is essential f or the enhancement of DNA encoded antigen-specific immunity by a booster im munization with recombinant E2 protein. Furthermore, the enhanced CD8(+) CT L and IgG2a responses induced by our combined vaccine regimens are closely associated with the protection of BALB/c mice from challenge with modified CT26 tumor cells expressing HCV E2 protein. Together, our results provide i mportant implications for vaccine development for many pathogens, including HCV, which require strong antibody and CTL responses.