Objectives To investigate the potential of interleukin (IL)-15 as a novel adjuvant for Mycobacterium tuberculosis (Mtb) antigen 85A (Ag85A) vaccine. Results C57BL/6 mice were intramuscularly immunized three times with a plasmid expressing the Ag85A-IL-15 fusion protein (pcDNA3.1-Ag85A-IL15), with the empty pcDNA3.1 vector and the pcDNA3.1-Ag85A as control. Mice vaccinated with pcDNA3.1-Ag85A-IL-15 generated more secretory IgA (sIgA) into their lung (209 +/- 21 mu g/ml) and acquired an enhanced serum IgG response to Ag85A. IgG2a/IgG1 ratios were upregulated, natural killer cell activity was augmented and Ag85A-specific splenic T cell proliferation was enhanced in these mice as well. Vaccination with pcDNA3.1-Ag85A-IL-15 promoted the polarization of CD4(+) T cells towards a Th1 type in the spleen, and significantly upregulated the serum level of interferon (IFN)-gamma (458 +/- 98 pg/ml), a typical Th1 cytokine. IFN-gamma-expressing CD8(+) cells were also increased in the spleen after pcDNA3.1-Ag85A-IL-15 immunization. Conclusions A superior immune type I response in mice vaccina Conclusions A superior immune type I response in mice vaccinated with plasmid Ag85A-IL-15 has been achieved.