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首页> 外文期刊>Infection and immunity >A Replication-Limited Recombinant Mycobacterium bovis BCG Vaccine against Tuberculosis Designed for Human Immunodeficiency Virus-Positive Persons Is Safer and More Efficacious than BCG
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A Replication-Limited Recombinant Mycobacterium bovis BCG Vaccine against Tuberculosis Designed for Human Immunodeficiency Virus-Positive Persons Is Safer and More Efficacious than BCG

机译：专为人类免疫缺陷病毒阳性人群设计的针对结核病的复制限制重组牛分枝杆菌卡介苗疫苗比卡介苗更安全，更有效

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Tuberculosis is the leading cause of death in AIDS patients, yet the current tuberculosis vaccine, Mycobacterium bovis bacillus Calmette-Guérin (BCG), is contraindicated for immunocompromised individuals, including human immunodeficiency virus-positive persons, because it can cause disseminated disease; moreover, its efficacy is suboptimal. To address these problems, we have engineered BCG mutants that grow normally in vitro in the presence of a supplement, are preloadable with supplement to allow limited growth in vivo, and express the highly immunoprotective Mycobacterium tuberculosis 30-kDa major secretory protein. The limited replication in vivo renders these vaccines safer than BCG in SCID mice yet is sufficient to induce potent cell-mediated and protective immunity in the outbred guinea pig model of pulmonary tuberculosis. In the case of one vaccine, rBCG(mbtB)30, protection was superior to that with BCG (0.3-log fewer CFU of M. tuberculosis in the lung [P < 0.04] and 0.6-log fewer CFU in the spleen [P = 0.001] in aerosol-challenged animals [means for three experiments]); hence, rBCG(mbtB)30 is the first live mycobacterial vaccine that is both more attenuated than BCG in the SCID mouse and more potent than BCG in the guinea pig. Our study demonstrates the feasibility of developing safer and more potent vaccines against tuberculosis. The novel approach of engineering a replication-limited vaccine expressing a recombinant immunoprotective antigen and preloading it with a required nutrient, such as iron, that is capable of being stored should be generally applicable to other live vaccine vectors targeting intracellular pathogens.
机译：结核病是艾滋病患者的主要死亡原因，但目前的免疫接种疫苗<牛>分枝杆菌卡尔梅特·盖林（BCG）>对免疫功能低下的人（包括人类免疫缺陷病毒阳性的人）是禁忌的可以引起传播性疾病;而且，其功效是次优的。为了解决这些问题，我们设计了BCG突变体，该突变体可在补充剂存在的情况下在体外正常生长，可预加载补充剂以使其在体内有限生长，并表达高度免疫保护的结核分枝杆菌 30-kDa主要分泌蛋白。体内有限的复制使这些疫苗比SCID小鼠中的BCG更安全，但足以在远距离豚鼠肺结核模型中诱导有效的细胞介导和保护性免疫。在一种疫苗rBCG（ mbtB ）30的情况下，其保护作用优于BCG（在肺部[ > P <0.04]，气溶胶激发动物的脾脏CFU减少了0.6-log [ P = 0.001]（三个实验的平均值））;因此，rBCG（ mbtB ）30是第一种活的分枝杆菌疫苗，在SCID小鼠中比BCG衰减更弱，在豚鼠中比BCG更有力。我们的研究表明开发针对肺结核的更安全，更有效的疫苗的可行性。工程化表达复制的免疫保护性抗原的复制受限疫苗并向其预载能够存储的所需营养物（如铁）的新颖方法通常应适用于靶向细胞内病原体的其他活疫苗载体。

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