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首页> 美国卫生研究院文献>Proceedings of the National Academy of Sciences of the United States of America >Recombinant bacillus Calmette–Guérin (BCG) vaccines expressing the Mycobacterium tuberculosis 30-kDa major secretory protein induce greater protective immunity against tuberculosis than conventional BCG vaccines in a highly susceptible animal model
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Recombinant bacillus Calmette–Guérin (BCG) vaccines expressing the Mycobacterium tuberculosis 30-kDa major secretory protein induce greater protective immunity against tuberculosis than conventional BCG vaccines in a highly susceptible animal model

机译：重组卡介苗（BCG）疫苗 表达结核分枝杆菌30 kDa 分泌蛋白诱导更大的针对 结核病比传统的卡介苗更易感 动物模型

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摘要

Tuberculosis (TB) continues to ravage humanity, causing 2 million deaths per year. A vaccine against TB more potent than the current live vaccine, bacillus Calmette–Guérin (BCG), is desperately needed. Using two commercially available strains of BCG as host strains, BCG Connaught and Tice, we have constructed two recombinant BCG vaccines stably expressing and secreting the 30-kDa major secretory protein of Mycobacterium tuberculosis (M. tb.), the primary causative agent of TB. We have tested the efficacy of the two strains in the highly susceptible guinea pig model of pulmonary TB, a model noteworthy for its close resemblance to human TB. Animals immunized with the recombinant BCG vaccines and challenged by aerosol with a highly virulent strain of M. tb. had 0.5 logs fewer M. tb. bacilli in their lungs and 1 log fewer bacilli in their spleens on average than animals immunized with their parental conventional BCG vaccine counterparts. Statistically, these differences were highly significant. Paralleling these results, at necropsy, animals immunized with the recombinant BCG vaccines had fewer and smaller lesions in the lung, spleen, and liver and significantly less lung pathology than animals immunized with the parental BCG vaccines. The recombinant vaccines are the first vaccines against TB more potent than the current commercially available BCG vaccines, which were developed nearly a century ago.
机译：结核病（TB）继续肆虐人类，每年造成200万人死亡。迫切需要一种比目前的活疫苗更有效的抗结核疫苗，即卡介苗。我们使用两种市售的BCG菌株BCG Connaught和Tice作为宿主菌株，我们构建了两种重组BCG疫苗，可稳定表达和分泌结核分枝杆菌（结核分枝杆菌）的30 kDa主要分泌蛋白。 。我们已经在肺结核的高度易感豚鼠模型中测试了这两种菌株的功效，该模型因其与人类结核病的相似性而值得注意。用重组BCG疫苗免疫的动物，并用高毒力的结核分枝杆菌气雾剂攻击。的M. tb减少了0.5个原木。与用其亲代常规BCG疫苗对应疫苗免疫的动物相比，其肺中的细菌总数和脾脏中的细菌总数平均减少1。从统计学上讲，这些差异非常重要。与这些结果平行的是，在尸检时，用重组BCG疫苗免疫的动物较少 以及肺，脾和肝的较小病变，并且明显 比用亲本BCG免疫的动物更少的肺部病理 疫苗。重组疫苗是针对结核病的首批疫苗 比目前市售的BCG疫苗更有效 是近一个世纪前开发的。

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