Recombinant bacillus Calmette-Guerin (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
Recombinant bacillus Calmette-Guerin (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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DOI：
10.1073/pnas.250480397
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发表时间：
2000-12-05
影响因子：
11.1
通讯作者：
Maslesa-Galic, S
中科院分区：
文献类型：
--
作者：
Horwitz, MA;Harth, G;Maslesa-Galic, S
结核病继续肆虐人类，每年造成200万人死亡。一种比目前的卡介苗(BCG)更有效的针对TN的疫苗。是非常需要的。以两株BCC为宿主株，构建了稳定表达和分泌TN主要病原体结核分枝杆菌(M.TB)30 kDa主要分泌蛋白的重组BCC疫苗。我们已经在高度敏感的肺结核病豚鼠模型上测试了这两种菌株的疗效，该模型值得注意的是它与人类结核病非常相似。用重组卡介苗免疫并用高毒力结核分枝杆菌气雾剂攻击的动物。减少了0.5个对数的M.TB。与亲代常规卡介苗免疫的动物相比，它们肺中的细菌和脾中的细菌平均少1个。从统计上看，这些差异非常显著。与这些结果相似的是，在尸检中，与亲本BCC疫苗免疫的动物相比，重组BCG疫苗免疫的动物在肺、脾和肝脏中的病变更少、更小，肺病理明显更少。重组疫苗是第一批比目前商业上可用的BCC疫苗更有效的结核病疫苗，后者是近一个世纪前开发的。
Tuberculosis (TB) continues to ravage humanity, causing 2 million deaths per year. A vaccine against Tn more potent than the current live vaccine, bacillus Calmette-Guerin (BCG). is desperately needed. Using two commercially available strains of BCC as host strains, BCC Connaught and Tice, we have constructed two recombinant BCC vaccines stably expressing and secreting the 30-kDa major secretory protein of Mycobacterium tuberculosis (M. tb.), the primary causative agent of Tn. 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 BCC vaccines. The recombinant Vaccines are the first Vaccines against TB more potent than the current commercially available BCC vaccines, which were developed nearly a century ago.