TY - JOUR
T1 - Efficacy of recombinant bacille Calmette-Guérin vaccine secreting interleukin-15/antigen 85B fusion protein in providing protection against Mycobacterium tuberculosis
AU - Tang, Ce
AU - Yamada, Hisakata
AU - Shibata, Kensuke
AU - Maeda, Naoyoshi
AU - Yoshida, Shinichi
AU - Wajjwalku, Worawidh
AU - Ohara, Naoya
AU - Yamada, Takeshi
AU - Kinoshita, Taroh
AU - Yoshikai, Yasunobu
N1 - Funding Information:
Financial support: This work was supported by the Program of Founding Research Centers for Emerging and Reemerging Infectious Diseases and was launched as a project commissioned by the Ministry of Education, Culture, Sports, Science and Technology, Japan, by Grant-in-Aid for Japan Society for Promotion of Science; Japanese Ministry of Education, Science and Culture (grants to Y.Y.).
PY - 2008/5/1
Y1 - 2008/5/1
N2 - 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-Guérin (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-2Db)- binding MPT64-specific CD8+ T cells producing interferon (IFN)-γ 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+ T cells producing IFN-γ 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 CD4+ 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.
AB - 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-Guérin (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-2Db)- binding MPT64-specific CD8+ T cells producing interferon (IFN)-γ 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+ T cells producing IFN-γ 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 CD4+ 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.
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U2 - 10.1086/586902
DO - 10.1086/586902
M3 - Article
C2 - 18422438
AN - SCOPUS:43049104974
VL - 197
SP - 1263
EP - 1274
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
SN - 0022-1899
IS - 9
ER -