The present study aims at establishing a novel vaccine procedure based on HBc-VLP-pulsed DCs. Immature mice BMDCs could capture HBc-VLP or HBc-VLP packaging CpG efficiently and present the antigen to syngeneic mice spleen T cells in vitro. Immunization with DCs showed that compared to VLP-pulsed DCs, VLP packaging CpG-pulsed DCs elicit stronger T-cell responses in vivo, as measured by both intracellular production of IFN-gamma and in vivo killing assays by Ag-specific T cells. In the B16-pIR-HH tumor therapy model, the growth of established tumors was significantly inhibited by single immunization of DCs pulsed with HBc-VLP packaged with CpG, resulting in significantly longer survival of immunized animals and strikingly, high frequencies (>10% of CD8(+) cells) of protective CTL could be induced and maintained. The mice immunized with DCs treated with HBc-VLP, however, trigger an antitumor effect at the early phase of vaccination, after 20 days of tumor injection, the tumor growth inhibition of VLP-pulsed DCs vaccination was decreased gradually and the fact could be interpreted by the decreasing number of antigen-specific CD8(+) T-cell and IFN-gamma(+)-producing CD8(+) T cell. This study therefore shows that the use of HBc-VLP packaging CpG-pulsed DCs could facilitate the development of effective T-cell-based vaccines.