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

Ce Tang, Hisakata Yamada, Kensuke Shibata, Naoyoshi Maeda, Shinichi Yoshida, Worawidh Wajjwalku, Naoya Ohara, Takeshi Yamada, Taroh Kinoshita, Yasunobu Yoshikai

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37 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1263-1274
Number of pages12
JournalJournal of Infectious Diseases
Volume197
Issue number9
DOIs
Publication statusPublished - May 1 2008

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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