The humoral and cytotoxic T-lymphocyte (CTL) responses have been shown to be determinant in the clearance of many viral infections and because of those characteristics, vaccine candidates against AIDS are designed to enhance both arms of the immune system. While a protocol of immunization able to confer protection in humans against HIV will have to await the results of current clinical trials, it remains important to identify protocols of immunization in animals that achieve significant levels of humoral and cellular immune responses to HIV. In this study we have carried out a comparative analysis of the immune responses elicited in mice immunized with recombinants based on the modified vaccinia virus Ankara strain (rMVA) versus the Western Reserve strain (WR) of vaccinia virus (rVV), both expressing a V3 loop multi-epitopic protein from eight different HIV isolates (TAB13). We found that during priming, rMVA elicited a two- to three-fold higher specific CD8+ T cell response than rVV. Similar enhancement was observed during priming with purified protein TAB13 followed by a booster with rMVA. The epitopes LR150, MN and IIIB, located at the ends and in the middle of the chimeric protein, were able to induce a specific CD8+ T cell response, both after priming or prime/booster with the recombinant viruses but not after prime/booster with TAB13. By examining the cytokine pattern, the immune response triggered by these vectors was of Th-1 type. Humoral immune responses were higher in animals immunized with TAB13/TAB13 or TAB13/rVV than in animals immunized with TAB13/rMVA. These findings demonstrate that during priming or in a prime/booster immunizations, rMVA is superior to rVV in the ability to enhance specific cellular responses to an HIV-1 protein, and that both humoral and cellular immune responses to theV3 loop epitope of HIV-1 Env can be obtained by priming with TAB13 followed by a booster with viral vectors.