Grode Leander, Seiler Peter, Baumann Sven, Hess Jürgen, Brinkmann Volker, Nasser Eddine Ali, Mann Peggy, Goosmann Christian, Bandermann Silke, Smith Debbie, Bancroft Gregory J, Reyrat Jean-Marc, van Soolingen Dick, Raupach Bärbel, Kaufmann Stefan H E
Max Planck Institute for Infection Biology, Berlin, Germany.
J Clin Invest. 2005 Sep;115(9):2472-9. doi: 10.1172/JCI24617. Epub 2005 Aug 18.
The tuberculosis vaccine Mycobacterium bovis bacille Calmette-Guérin (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 (DeltaureC hly+ rBCG) vaccine, providing an intraphagosomal pH closer to the acidic pH optimum for Hly activity, exhibited still higher vaccine efficacy than parental BCG. DeltaureC 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 DeltaureC hly+ rBCG as compared with parental BCG is primarily based on improved cross-priming, which causes enhanced T cell-mediated immunity.
结核疫苗牛分枝杆菌卡介苗（BCG）配备了单核细胞增生李斯特菌的膜穿孔溶菌酶（Hly），已证明其可增强对结核分枝杆菌的保护作用。经气溶胶攻击后，分泌Hly的重组卡介苗（hly+rBCG）疫苗对结核分枝杆菌气溶胶感染的保护作用明显优于亲本卡介苗菌株。同基因的、脲酶C缺陷的hly+rBCG（DeltaureC hly+rBCG）疫苗，其吞噬体内pH值更接近Hly活性的最佳酸性pH值，表现出比亲本卡介苗更高的疫苗效力。DeltaureC hly+rBCG还能对结核分枝杆菌北京/W基因型家族的一个成员产生深度保护，而亲本卡介苗则不能始终如此。Hly不仅促进抗原转运到细胞质中，还能诱导被感染巨噬细胞凋亡。我们得出结论，与亲本卡介苗相比，DeltaureC hly+rBCG具有更高的疫苗效力，主要是基于改善的交叉呈递，这导致T细胞介导的免疫增强。
