DNA and RNA Vaccines: Current Status, Quality Requirements and Specific Aspects of Preclinical Studies

Abstract

This review focuses on DNA and RNA vaccines whose potential use was first considered at the end of the 20th century. However, not a single bacterial plasmid-based or mRNA vaccine has been used since that time in public healthcare for the prevention of infectious diseases. Nevertheless, vaccines containing recombinant nucleic acids as the active ingredient still attract interest due to the possibility of rapid development, low-cost production, safety of the technology and the potential to activate cellular and humoral immunity. Recent technological advances have largely overcome the problems of low immunogenicity, instability, and difficulties with the delivery of DNA and RNA vaccines in humans. The aim of this review was to present the main strategies of development of DNA and RNA vaccines designed to prevent infectious diseases, and to summarise requirements for the quality control and preclinical studies. The article examines the general principles of creation of plasmid vectors encoding protective antigens. It describes new technologies used in the creation of DNA vaccines with plasmids encoding an attenuated virus genome (iDNA and PPLAV), and RNA vaccines based on mRNA and self-amplifying RNAs. The article presents current regulatory requirements for the choice of quality parameters to be tested and the general principles of preclinical studies of DNA and RNA vaccines.

DNA vaccines and recombinant allergens with reduced allergenic activity treat allergies

“…Compared to conventional protein-based vaccines, DNA vaccines are more stable, economical, easier to manufacture, and safer to handle. The classical methods of vaccine administration are intramuscular, intradermal, and subcutaneous injections, which are primarily targeted to myocytes and keratinocytes, as well as APC [41,42]. It is believed that antigen presentation during DNA vaccination may occur via three possible mechanisms:…”

“…DNA vaccination studies have shown that the activation of CD8+ cytotoxic T lymphocytes is largely dependent on dendritic cells, rather than being induced by somatic cells [41,42,43]. This presentation shapes the appropriate pattern of cytokine regulation of the immune response.…”

“…The above immunological mechanisms with existing pronounced skew of the Th1/Th2 ratio towards Th2 in patients with IgE-mediated allergic reactions should contribute to the formation of a change in the immunological response to the allergen and the synthesis of specific IgG [4]. However, after DNA vaccination, low antibody production is often found in humans and large animals [42,44].…”

“…Various methods are used to enhance the immunogenicity of DNA vaccines [42,[44][45][46]. One of the methods was demonstrated using the example of preparing a vaccine from the DNA of immunodominant epitopes CryJ1 or CryJ2 of Japanese cedar pollen allergens with lysosomal-associated membrane protein 1 (LAMP-1), a resident protein of lysosomes.…”