This study assessed and compared the immunogenicity of various immunization strategies in mice using combinations of re- combinant DNA (pCCMp24) and recombinant attenuated vaccinia virus Tian Tan (rddVTT_ccMpe4). Intramuscular immuniza- tion was performed on days 0 (prime) and 21 (boost). The immunogenicity of the vaccine schedules was determined by meas- uring human immunodeficiency virus (HIV)-specific binding antibody levels and cytokine (interleukin-2 and interleukin-4) concentrations in peripheral blood, analyzing lymphocyte proliferation capacity against HIV epitopes and CD4~/CD8+cell ratio, and monitoring interferon-gamma levels at different times post-immunization. The results showed that pCCMp24, rddVTT.ccMp24 and their prime-boost immunization induced humoral and cellular immune responses. The pCCMp24/ rddVTT.ccMp24 immunization strategy increased CD8+ T cells and induced more IFN-7-secreting cells compared with sin- gle-shot rDNA. The prime-boost immunization strategy also induced the generation of cellular immunological memory to HIV epitope peptides. These results demonstrated that prime-boost immunization with rDNA and rddVTT_ccMp24 had a tendency to induce greater cellular immune response than single-shot vaccinations, especially IFN-7 response, providing a basis for further studies.