Mumper R J, Ledebur H C
College of Pharmacy, University of Kentucky, Lexington, Kentucky 40536-0082, USA.
Mol Biotechnol. 2001 Sep;19(1):79-95. doi: 10.1385/MB:19:1:079.
Positive human clinical data using biolistic-mediated gene transfer (i.e., gene gun) to administer a nucleic acid-based Hepatitis B vaccine has validated genetic immunization as an effective clinical vaccine modality. Although the precise mechanism of action has yet to be determined, preclinical studies using jet injection have indicated that direct targeting of resident antigen presenting cells (Langerhan's cells) in the skin as the primary immunological driving force for the potent and long-lived immune response. Moreover, positive results with topical delivery of genetic vaccines and ex vivo loading of dendritic cells with antigen has strengthened the movement toward directly targeting antigen presenting cells as a means to amplify, control, and mediate the immunological consequences of prophylactic and/or therapeutic genetic vaccines. Despite these encouraging results with the gene gun, it is unclear whether this technology will translate into commercially available vaccines due to potential product development barriers such as cost and convenience. It is clear that safety concerns in using genetic approaches to treat and prevent disease have highlighted the need for strict product requirements for genetic vaccines. A plausible strategy to meet these requirements is to combine controlled plasmid delivery systems with tissue-specific gene expression systems.
使用生物弹道介导的基因转移（即基因枪）来施用基于核酸的乙型肝炎疫苗的人体临床阳性数据已证实基因免疫是一种有效的临床疫苗模式。尽管确切的作用机制尚未确定，但使用喷射注射的临床前研究表明，皮肤中驻留抗原呈递细胞（朗格汉斯细胞）的直接靶向是强效和持久免疫反应的主要免疫驱动力。此外，基因疫苗局部递送和树突状细胞体外负载抗原的阳性结果，加强了将直接靶向抗原呈递细胞作为一种放大、控制和介导预防性和/或治疗性基因疫苗免疫后果的手段的趋势。尽管基因枪取得了这些令人鼓舞的结果，但由于成本和便利性等潜在产品开发障碍，尚不清楚这项技术是否会转化为商业可用疫苗。显然，使用基因方法治疗和预防疾病的安全问题突出了对基因疫苗严格产品要求的必要性。满足这些要求的一个合理策略是将可控质粒递送系统与组织特异性基因表达系统相结合。
