ABSTRACT
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.