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首页> 美国卫生研究院文献>BioMed Research International >Assessment of the Genetic Diversity of Mycobacterium tuberculosis esxA esxH and fbpB Genes among Clinical Isolates and Its Implication for the Future Immunization by New Tuberculosis Subunit Vaccines Ag85B-ESAT-6 and Ag85B-TB10.4
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Assessment of the Genetic Diversity of Mycobacterium tuberculosis esxA esxH and fbpB Genes among Clinical Isolates and Its Implication for the Future Immunization by New Tuberculosis Subunit Vaccines Ag85B-ESAT-6 and Ag85B-TB10.4

机译：临床分离株中结核分枝杆菌esxAesxH和fbpB基因的遗传多样性评估及其对新型结核亚单位疫苗Ag85B-ESAT-6和Ag85B-TB10.4未来免疫的意义

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The effort to develop a tuberculosis (TB) vaccine more effective than the widely used Bacille Calmette-Guérin (BCG) has led to the development of two novel fusion protein subunit vaccines: Ag85B-ESAT-6 and Ag85B-TB10.4. Studies of these vaccines in animal models have revealed their ability to generate protective immune responses. Yet, previous work on TB fusion subunit vaccine candidate, Mtb72f, has suggested that genetic diversity among M. tuberculosis strains may compromise vaccine efficacy. In this study, we sequenced the esxA, esxH, and fbpB genes of M. tuberculosis encoding ESAT-6, TB10.4, and Ag85B proteins, respectively, in a sample of 88 clinical isolates representing 57 strains from Ark, USA, and 31 strains from Turkey, to assess the genetic diversity of the two vaccine candidates. We found no DNA polymorphism in esxA and esxH genes in the study sample and only one synonymous single nucleotide change (C to A) in fbpB gene among 39 (44.3%) of the 88 strains sequenced. These data suggest that it is unlikely that the efficacy of Ag85B-ESAT-6 and Ag85B-TB10.4 vaccines will be affected by the genetic diversity of M. tuberculosis population. Future studies should include a broader pool of M. tuberculosis strains to validate the current conclusion.
机译：开发比广泛使用的卡介苗（BCG）更有效的结核病（TB）疫苗的努力已导致开发了两种新型融合蛋白亚基疫苗：Ag85B-ESAT-6和Ag85B-TB10.4。在动物模型中对这些疫苗的研究表明它们具有产生保护性免疫反应的能力。然而，先前有关结核病融合亚基疫苗候选药物Mtb72f的研究表明，结核分枝杆菌菌株之间的遗传多样性可能会损害疫苗的功效。在这项研究中，我们在88个临床分离株的样本中对结核分枝杆菌的esxA，esxH和fbpB基因进行了编码，分别编码ESAT-6，TB10.4和Ag85B蛋白，分别来自57个来自美国Ark和31个菌株。来自土耳其的菌株，以评估两种候选疫苗的遗传多样性。我们在研究样本的esxA和esxH基因中未发现DNA多态性，在88株测序菌株中的39株（44.3％）中，仅fbpB基因中一个同义单核苷酸变化（C到A）。这些数据表明，Ag85B-ESAT-6和Ag85B-TB10.4疫苗的功效不太可能受到结核分枝杆菌种群遗传多样性的影响。未来的研究应包括更多的结核分枝杆菌菌株，以验证当前的结论。

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