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首页> 外文期刊>Vaccine >The BCG Delta BCG1419c strain, which produces more pellicle in vitro, improves control of chronic tuberculosis in vivo
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The BCG Delta BCG1419c strain, which produces more pellicle in vitro, improves control of chronic tuberculosis in vivo

机译：BCG Delta BCG1419c菌株可在体外产生更多的表皮，可改善体内对慢性肺结核的控制

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Mycobacterium tuberculosis (Mtb) has been a threat to humans since ancient times, and it is the main causative agent of tuberculosis (TB). Until today, the only licensed vaccine against Mtb is the live attenuated M. bovis Bacillus Calmette-Guerin (BCG), which has variable levels of protection against the pulmonary form of infection. The quest for a new vaccine is a priority given the rise of multidrug-resistant Mtb around the world, as well as the tremendous burden imposed by latent TB. The objective of this study was to evaluate the immunogenicity and capacity of protection of a modified BCG strain (BCG Delta BCG1419c) lacking the c-di-GMP phosphodiesterase gene BCG1419c, in diverse mice models. In a previous report, we have shown that BCGABCG1419c was capable of increasing biofilm production and after intravenous infection of immunocompetent mice; this strain persisted longer in lungs than parental BCG Pasteur. This led us to hypothesize that BCG Delta BCG1419c might therefore possess some advantage as vaccine candidate. Our results in this report indicate that compared to conventional BCG, vaccination with BCG Delta BCG1419c induced a better activation of specific T-lymphocytes population, was equally effective in preventing weight loss despite being used at lower dose, reduced tissue damage (pneumonic scores), increased local IFNI gamma(+) T cells, and diminished bacterial burden in lungs of BALB/c mice infected intratracheally with high dose Mtb H37Rv to induce progressive TB. Moreover, vaccination with BCG Delta BCG1419c improved resistance to reactivation after immunosuppression induced by corticosterone in a murine model of chronic infection similar to latent TB. Furthermore, despite showing increased persistence in immunocompetent mice, BCG Delta BCG1419c was as attenuated as parental BCG in nude mice. To our knowledge, this is the first demonstration that a modified BCG vaccine candidate with increased pellicle/biofilm production has the capacity to protect against Mtb challenge in chronic and reactivation models of infection. (C) 2016 Elsevier Ltd. All rights reserved.
机译：自古以来，结核分枝杆菌（Mtb）一直对人类构成威胁，它是结核病（TB）的主要病原体。直到今天，针对Mtb的唯一获许可的疫苗是减毒活牛原芽孢杆菌Calmette-Guerin（BCG），它对肺部感染的保护水平不同。鉴于世界范围内具有多重耐药性的Mtb的崛起以及潜在结核病带来的巨大负担，寻求新疫苗是当务之急。这项研究的目的是在不同的小鼠模型中评估缺少c-di-GMP磷酸二酯酶基因BCG1419c的改良BCG株（BCG Delta BCG1419c）的免疫原性和保护能力。在以前的报告中，我们表明BCGABCG1419c能够增加生物膜的产生，并且可以在免疫感染小鼠的静脉内感染后增加。该菌株在肺部的持续时间要长于父母的BCG Pasteur。这使我们假设BCG Delta BCG1419c可能因此具有候选疫苗的优势。我们在这份报告中的结果表明，与传统BCG相比，接种BCG Delta BCG1419c可以更好地激活特定T淋巴细胞群，尽管以较低的剂量使用也可以有效地防止体重减轻，减少了组织损伤（肺炎评分），增加气管内感染高剂量Mtb H37Rv感染的BALB / c小鼠的局部IFNIγ（+）T细胞，并减少肺部细菌负担，以诱导进行性TB。此外，在类似于潜伏性结核病的慢性感染小鼠模型中，接种BCG Delta BCG1419c疫苗可提高皮质酮诱导的免疫抑制后对再激活的抵抗力。此外，尽管在免疫活性小鼠中显示出增加的持久性，但是在裸鼠中，BCG Delta BCG1419c与亲本BCG一样弱。据我们所知，这是首次证明改良的BCG候选疫苗具有更高的防护膜/生物膜产生能力，能够在慢性和再感染模型中防御Mtb攻击。 （C）2016 Elsevier Ltd.保留所有权利。

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