Brucellosis: the case for live, attenuated vaccines.
Brucellosis: the case for live, attenuated vaccines.
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DOI：
10.1016/j.vaccine.2009.08.058
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发表时间：
2009-11-05
期刊：
影响因子：
5.5
通讯作者：
Rice-Ficht AC
中科院分区：
文献类型：
--
作者：
Ficht TA;Kahl-McDonagh MM;Arenas-Gamboa AM;Rice-Ficht AC
动物布鲁氏菌病的成功控制和相关的人类暴露的减少限制了人类布鲁氏菌病疫苗的开发。然而，布鲁氏菌在生物恐怖主义或生物战中的潜在用途表明，直接干预战略是必要的。虽然主要的方法已经探索了减毒活疫苗的使用，但与其使用相关的副作用阻止了在人类中的广泛使用。对人类安全使用的布鲁氏菌减毒活疫苗的开发集中在生存所需的重要基因的缺失上。然而，缺失突变体的安全性增强通常与疗效降低相关。由于这个原因，最近的努力试图通过微囊化将安全、无副作用且在人中有效的减毒活疫苗的最佳特征与增强的免疫刺激结合联合收割机。该方法的竞争优势和创新在于：（1）使用高度减毒、安全、基因敲除的活布鲁氏菌突变体;（2）采用独特的一次性封闭系统技术进行生产;（3）以新型微囊化介导的控释配方经口/鼻内给药，以最佳方式提供保护性免疫所需的长期粘膜免疫刺激。基于初步数据，假定这样的疫苗递送系统可以是储存稳定的，口服或鼻内施用，并且通常适用于许多药剂。
The successful control of animal brucellosis and associated reduction in human exposure has limited the development of human brucellosis vaccines. However, the potential use of Brucella in bioterrorism or biowarfare suggests that direct intervention strategies are warranted. Although the dominant approach has explored the use of live attenuated vaccines, side-effects associated with their use has prevented widespread use in humans. Development of live, attenuated Brucella vaccines that are safe for use in humans has focused on the deletion of important genes required for survival. However, the enhanced safety of deletion mutants is most often associated with reduced efficacy. For this reason recent efforts have sought to combine the optimal features of a attenuated live vaccine that is safe, free of side effects and efficacious in humans with enhanced immune stimulation through microencapsulation. The competitive advantages and innovations of this approach are: (1) use of a highly attenuated, safe, gene knockout, live Brucella mutants; (2) manufacturing with unique disposable closed system technologies, and (3) oral/intranasal delivery in a novel microencapsulation-mediated controlled release formula to optimally provide the long term mucosal immunostimulation required for protective immunity. Based upon preliminary data, it is postulated that such vaccine delivery systems can be storage stable, administered orally or intranasally, and generally applicable to a number of agents.
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3.1
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