Efficacy of recombinant bacille Calmette-Guérin vaccine secreting interleukin-15/antigen 85B fusion protein in providing protection against Mycobacterium tuberculosis.
Efficacy of recombinant bacille Calmette-Guérin vaccine secreting interleukin-15/antigen 85B fusion protein in providing protection against Mycobacterium tuberculosis.
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DOI：
10.1086/586902
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发表时间：
2008-05
期刊：
影响因子：
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通讯作者：
Ce Tang;H. Yamada;K. Shibata;N. Maeda;S. Yoshida;W. Wajjwalku;N. Ohara;Takeshi Yamada;T. Kinoshita;Y. Yoshikai
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文献类型：
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作者：
Ce Tang;H. Yamada;K. Shibata;N. Maeda;S. Yoshida;W. Wajjwalku;N. Ohara;Takeshi Yamada;T. Kinoshita;Y. Yoshikai
对结核分枝杆菌的保护不仅依赖于CD4+T辅助细胞1型(Th1)细胞，还依赖于CD8+T细胞。白介素15在CD8+T细胞的记忆维持中起着重要作用。在本研究中，我们检测了分泌融合蛋白抗原(Ag)85B的重组牛分枝杆菌卡介苗(RBCG)对小鼠IL-15(rBCG-Ag85B-IL15)的保护作用。RBCG-Ag85B-IL15免疫小鼠后，主要组织相容性(MHC)Ib(H2-M3)结合TB2或MHC Ia(H-2DB)结合MPT64特异性CD8+T细胞产生干扰素-γ的水平显著高于rBCG分泌Ag85B(rBCG-Ag85B)免疫后。RBCG-Ag85B-IL15免疫小鼠产生干扰素-γ的纯化蛋白衍生物或Ag85B特异的CD4+T细胞水平也高于rBCG-Ag85B免疫小鼠。RBCG-Ag85B-IL15免疫小鼠表现出比rBCG-Ag85B免疫小鼠更强的CD8+和CD4+T细胞应答，并对结核分枝杆菌气管内攻击具有较强的肺保护作用。因此，rBCG-Ag85B-IL15疫苗可诱导有效的细胞免疫，有望成为一种有效的结核病疫苗。
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)-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+ T cells 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 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.