Institute of Fundamental Sciences, Massey University, 11222 Private Bag, Palmerston North, New Zealand.
AgResearch, Hopkirk Research Institute, Grasslands Research Centre, 11008 Private Bag, Palmerston North, New Zealand.
Microb Biotechnol. 2017 Nov;10(6):1434-1440. doi: 10.1111/1751-7915.12754. Epub 2017 Jul 17.
In 2015, there were an estimated 10.4 million new tuberculosis (TB) cases and 1.4 million deaths worldwide. Bacille Calmette-Guérin (BCG), an attenuated strain of Mycobacterium bovis, is the vaccine available against TB, but it is insufficient for global TB control. This study evaluated the immunogenicity of the Mycobacterium tuberculosis antigen Rv1626 in mice while assessing the effect of co-delivering either Cpe30 (immunostimulatory peptide), CS.T3 (promiscuous T helper epitope) or flagellin (TLR5 agonist) or a combination of all three immunostimulatory agents. Rv1626 and the respective immunostimulatory proteins/peptides were co-displayed on polyhydroxybutyrate beads assembled inside an engineered endotoxin-free mutant of Escherichia coli. Mice vaccinated with these beads produced immune responses biased towards Th1-/Th17-type responses, but inclusion of Cpe30, CS.T3 and flagellin did not enhance immunogenicity of the Rv1626 protein. This was confirmed in a M. bovis challenge experiment in mice, where Rv1626 beads reduced bacterial cell counts in the lungs by 0.48 log compared with the adjuvant alone control group. Co-delivery of immunostimulatory peptides did not further enhance protective immunity.
2015 年，全球估计有 1040 万例新结核病（TB）病例和 140 万人死亡。卡介苗（BCG），一种减毒的牛分枝杆菌菌株，是预防结核病的疫苗，但不足以控制全球结核病。本研究评估了分枝杆菌抗原 Rv1626 在小鼠中的免疫原性，同时评估了共递送 Cpe30（免疫刺激肽）、CS.T3（混杂 T 辅助表位）或鞭毛蛋白（TLR5 激动剂）或这三种免疫刺激剂的组合对其的影响。Rv1626 和各自的免疫刺激蛋白/肽共同展示在聚羟基丁酸酯珠上，这些珠组装在一个工程化的内毒素免费突变大肠杆菌内。用这些珠粒接种的小鼠产生了偏向于 Th1-/Th17 型反应的免疫反应，但包含 Cpe30、CS.T3 和鞭毛蛋白并没有增强 Rv1626 蛋白的免疫原性。这在小鼠牛分枝杆菌挑战实验中得到了证实，其中 Rv1626 珠粒使肺部细菌细胞计数减少了 0.48 对数与单独佐剂对照组相比。免疫刺激性肽的共递送并没有进一步增强保护性免疫。
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