DNA Vaccine Technologies: Design and Delivery

The COVID-19 pandemic has triggered the development of new directions in vaccine development, among which DNA- and mRNA-based technologies are particularly noteworthy. The platform based on DNA vaccines is developing particularly intensively due to their high stability at ambient temperature and the ability to activate both humoral and cellular immunity. The full cycle of DNA vaccine creation, which includes the construction of plasmid DNA, obtaining a producer strain, fermentation, and purification, takes 2‒4 weeks. In addition, the production technology of such vaccines does not require working with dangerous pathogens, which significantly simplifies the process of their production and reduces the overall cost. Over more than 30 years of rapid development, DNA vaccine technology continues to undergo changes. Currently, there is a licensed DNA vaccine for the prevention of COVID-19, and many candidate prophylactic vaccines against viral and bacterial diseases are in clinical trials. This review covers not only the principles of constructing plasmid DNA vaccines, but also new technologies for obtaining DNA constructs, such as minicircular DNA, MIDGE DNA, and DoggyboneTM DNA. New types of DNA vaccines are interesting because they consist only of the most essential elements for activating the immune response. Such constructs completely lack the sequences necessary for the production of plasmid DNA in bacterial cells, for example, the antibiotic resistance gene. One of the key problems in the development of a DNA vaccine is the method of its delivery to target cells. Currently, various delivery methods are used, both chemical and physical, which are rapidly developing and have already proven themselves to be reliable and effective. The characteristics of some of the most promising methods are also presented in this review.