DNA疫苗的作用机制

DNA vaccines: mechanisms of action

背景:1990年Wolff等发现将RNA和DNA表达载体直接注射小鼠骨骼肌,可以检测到相应的蛋白表达,这揭示DNA可以直接用于疾病的治疗和免疫,基因疗法和DNA疫苗应运而生。随着近年来的研究发展,DNA疫苗迅速显示出了几个显著特点(包括低成本、生产制造的简单便捷、及稳定性),使其成为未来解决全球卫生问题的最有前景的方法之一。目的:从来自细菌DNA的先天免疫信号、DNA疫苗直接转染组织细胞、交叉激活和交叉呈递机制、DNA疫苗直接转染APCs及细胞凋亡机制5个方面综述DNA疫苗的作用机制。方法:第一作者通过电子计算机检索2000年1月至2017年6月为止Pub Med数据库及CNKI中国期刊全文数据库收录的与DNA疫苗有关的文献。英文检索词"DNA vaccine、gene vaccine、DNA plasmid、cross-presentation、transfection、apoptosis",中文检索词"基因疫苗、DNA疫苗、DNA质粒、交叉呈递、细胞凋亡、细胞转染",总计得到中英文文献105篇,47篇文献符合标准。结果与结论:在DNA疫苗发展的20多年里,研究人员发现人类DNA疫苗与传统蛋白疫苗相比,只能获得有限的抗体表达水平。在DNA疫苗作用机制中DNA转染组织细胞或者专职抗原呈递细胞、专职抗原呈递细胞交叉激活及交叉呈递DNA编码的抗原,同时DNA激活先天的免疫应答、诱导细胞凋亡,基于这些理论的研究为将来改善DNA疫苗的免疫效果提供理论支持。

BACKGROUND:In 1990,Wolff et al.reported that DNA was examined as a gene therapy tool,and emerged as a promising therapy after observations that simple injection of naked plasmid DNA and RNA led to profound transgene expression in vivo.DNA vaccines are recognized for harboring several distinguishing characteristics and advantages(including low cost,ease and rapidity of manufacturing,and stability)making them a method for addressing global health threats in the future.OBJECTIVE:To review the status and research progress of DNA vaccines in the view of mechanism of action:innate immune signaling from bacterial DNA,transfecting somatic cell by DNA vaccines,cross-presentation and cross-activation,transfecting antigen presenting cells by DNA vaccines,and apoptosis.METHODS:The first author retrieved the databases of PubMed and CNKI for the articles concerning DNA vaccines published between January 2000 and June 2017 using the keywords of“DNA vaccine,gene vaccine,plasmid DNA,cross-presentation,transfection,apoptosis”in English and Chinese,respectively.A total of 105 literatures were searched,and 47 eligible articles were included in accordance with the inclusion criteria.RESULTS AND CONCLUSION:The immunogenicity of DNA vaccines in humans has been limited by low expression levels of antigen,in comparison with the conventional protein vaccines in the past two decades.Studies on the mechanism of action of DNA vaccines in terms of antigen-presenting cell types able to cross-present DNA-encoded antigens,the activation of innate immune responses due to DNA itself and induction of cell apoptosis have suggested the opportunities to increase the immunogenicity of these vaccines.