Becker Pablo Daniel, Noerder Miriam, Guzmán Carlos Alberto
Department of Vaccinology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
Hum Vaccin. 2008 May-Jun;4(3):189-202. doi: 10.4161/hv.4.3.6314. Epub 2010 May 14.
The so-called DNA vaccination represents one of the most notable tools under development in the field of vaccinology. The concept of administering the gene coding for any given protective antigen and make responsible vaccinee's own cells to produce the protein appeals as too simple to be true. Indeed, the implementation of this approach for mass vaccination should overcome several bottlenecks, such as need of high dosages and poor immunogenicity. In this context, the use of live attenuated bacteria as delivery system for plasmid DNA has emerged as a promising alternative to overcome many of those pitfalls. In addition, this approach is not only amenable for mucosal administration, but allows to specifically target professional antigen presenting cells. This results in their transfection, as well as in their activation and maturation, due to their built-in adjuvant properties resulting from the stimulation of pattern recognition receptors. This chapter discusses the specific features that should be taken into consideration when designing a plasmid vector, current candidate bacterial carriers for DNA delivery and main safety issues.
所谓的DNA疫苗接种是疫苗学领域正在开发的最显著工具之一。给予编码任何特定保护性抗原的基因并让接种疫苗者自身的细胞产生蛋白质的概念听起来太过简单而不太可能实现。事实上,将这种方法用于大规模疫苗接种需要克服几个瓶颈,比如需要高剂量以及免疫原性较差。在这种情况下,使用减毒活细菌作为质粒DNA的递送系统已成为克服许多此类缺陷的一种有前景的替代方法。此外,这种方法不仅适用于黏膜给药,还能特异性靶向专职抗原呈递细胞。由于刺激模式识别受体产生的内在佐剂特性,这会导致它们被转染,以及激活和成熟。本章讨论了设计质粒载体时应考虑的具体特征、当前用于DNA递送的候选细菌载体以及主要安全问题。