Increased vaccine efficacy against tuberculosis of recombinant Mycobacterium bovis bacille Calmette-Guerin mutants that secrete listeriolysin
Increased vaccine efficacy against tuberculosis of recombinant Mycobacterium bovis bacille Calmette-Guerin mutants that secrete listeriolysin
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DOI：
10.1172/jci24617
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发表时间：
2005-09-01
影响因子：
15.9
通讯作者：
Kaufmann, SHE
中科院分区：
文献类型：
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作者：
Grode, L;Seiler, P;Kaufmann, SHE
牛分枝杆菌卡介苗(BCG)中含有单核细胞增生性李斯特菌膜穿孔素(HLY)，可增强对结核分枝杆菌的免疫保护作用。在气雾剂攻击后，分泌HLY(+)的重组卡介苗(HLY(+)rBCG)被证明比亲本卡介苗对气雾剂感染结核分枝杆菌有显著更好的保护作用。同基因，尿素酶C缺乏的HLY(+)rBCG(Delta UREC HLY(+)rBCG)疫苗，其吞噬体内的pH更接近HLY活性的最适酸性pH，显示出比亲本BCG更高的疫苗效力。Delta UREC HLY(+)rBCG也对结核分枝杆菌Beijing/W基因家族的一名成员产生了深刻的保护作用，而双亲BCG未能始终如一地做到这一点。HLY不仅能促进抗原移位到胞浆内，还能促进感染巨噬细胞的凋亡。我们的结论是，Delta UREC HLY(+)rBCG与亲本BCG相比，其优越的疫苗效果主要是基于改进的交叉免疫，这导致了T细胞介导的免疫增强。
The tuberculosis vaccine Mycobacterium bovis bacille Calmette-Guerin (BCG) was equipped with the membrane-perforating listeriolysin (Hly) of Listeria monocytogenes, which was shown to improve protection against Mycobacterium tuberculosis. Following aerosol challenge, the Hly-secreting recombinant BCG (hly(+) rBCG) vaccine was shown to protect significantly better against aerosol infection with M. tuberculosis than did the parental BCG strain. The isogenic, urease C-deficient hly(+) rBCG (Delta ureC hly(+) rBCG) vaccine, providing an intraphagosomal pH closer to the acidic pH optimum for Hly activity, exhibited still higher vaccine efficacy than parental BCG. Delta ureC hly(+) rBCG also induced profound protection against a member of the M. tuberculosis Beijing/W genotype family while parental BCG failed to do so consistently. Hly not only promoted antigen translocation into the cytoplasm but also apoptosis of infected macrophages. We concluded that superior vaccine efficacy of Delta ureC hly(+) rBCG as compared with parental BCG is primarily based on improved cross-priming, which causes enhanced T cell-mediated immunity.