Efficacy of recombinant bacille Calmette-Guerin vaccine secreting interleukin-15/antigen 85B fusion protein in providing protection against Mycobacterium tuberculosis

Protection against Mycobacterium tuberculosis not only depends on CD4(+) T helper type 1 (Th1) cells but, also, on CD8(+) T cells. Interleukin (IL)-15 has an important function in the maintenance of memory CD8(+) T cells. In the present study, we examined the efficacy of recombinant Mycobacterium bovis bacille Calmette-Guerin (rBCG) secreting fusion protein antigen (Ag) 85B murine IL-15 (rBCG-Ag85B-IL15) in providing protection against M. tuberculosis infection. The levels of major histocompatibility (MHC) class Ib (H2-M3)-binding TB2- or MHC class Ia (H-2D(b))-binding MPT64-specific CD8(+) T cells producing interferon (IFN)-gamma were significantly higher after immunization with rBCG-Ag85B-IL15 than after immunization with rBCG secreting Ag85B (rBCG-Ag85B). The levels of purified protein derivative-or Ag85B-specific CD4(+) Tcells producing IFN-gamma were also higher in mice immunized with rBCG-Ag85B-IL15 than in mice immunized with rBCG-Ag85B. Mice immunized with rBCG-Ag85B-IL15 exhibited CD8(+) and CD+ T cells responses that were stronger than those in mice immunized with rBCG-Ag85B, as well as robust protection in the lung against intratracheal challenge of M. tuberculosis. Thus, rBCG-Ag85B-IL15 vaccination capable of inducing efficient cell-mediated immunity might be used as an effective vaccine for tuberculosis.