Live-attenuated Salmonella as a prototype vaccine vector for passenger immunogens in humans: are we there yet?
Live-attenuated Salmonella as a prototype vaccine vector for passenger immunogens in humans: are we there yet?
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DOI：
10.1586/14760584.6.3.431
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发表时间：
2007-06
影响因子：
6.2
通讯作者：
G. Lewis
中科院分区：
文献类型：
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作者：
G. Lewis
自从通过重组DNA方法创建减毒活细菌疫苗的第一个I期临床试验以来，已经将近20年了，为使用这些生物体作为乘客抗原的粘膜递送载体打开了大门。在此期间，许多动物研究表明了这种方法的可行性。这些研究包括表明细菌可以递送由细菌本身表达的抗原，以及细菌可以递送DNA疫苗以在靶真核细胞中表达。伴随的研究已经鉴定了许多减毒突变，其使得细菌载体在人类中既安全又具有免疫原性。这两种研究途径都表明这种方法对粘膜疫苗开发的重要前景;然而，这种前景在人体临床试验水平上仍然很大程度上没有实现。本文概述了这个问题的历史，并指出可能的解决方案，使用沙门氏菌疫苗载体为原型。
It has been nearly 20 years since the first Phase I clinical trial of a live-attenuated bacterial vaccine was created by recombinant DNA methods, opening the door to the use of these organisms as mucosal delivery vehicles for passenger antigens. Over this time, a number of animal studies have indicated the feasibility of this approach. These include studies showing that bacteria can deliver antigens expressed by the bacterium itself and that bacteria can deliver DNA vaccines to be expressed in target eukaryotic cells. Concomitant studies have identified a number of attenuating mutations that render the bacterial vectors both safe and immunogenic in humans. Both avenues of research indicate the significant promise of this approach to mucosal vaccine development; however, this promise remains largely unrealized at the level of human clinical trials. This review sketches the history of this problem and points toward possible solutions using Salmonella vaccine vectors as the prototypes.