DNA Vaccines: Their Formulations, Engineering and Delivery

Abstract

The concept of DNA vaccination was introduced in the early 1990s. Since then, advancements in the augmentation of the immunogenicity of DNA vaccines have brought this technology to the market, especially in veterinary medicine, to prevent many diseases. Along with the successful COVID mRNA vaccines, the first DNA vaccine for human use, the Indian ZyCovD vaccine against SARS-CoV-2, was approved in 2021. In the current review, we first give an overview of the DNA vaccine focusing on the science, including adjuvants and delivery methods. We then cover some of the emerging science in the field of DNA vaccines, notably efforts to optimize delivery systems, better engineer delivery apparatuses, identify optimal delivery sites, personalize cancer immunotherapy through DNA vaccination, enhance adjuvant science through gene adjuvants, enhance off-target and heritable immunity through epigenetic modification, and predict epitopes with bioinformatic approaches. We also discuss the major limitations of DNA vaccines and we aim to address many theoretical concerns.

DNA Vaccine Encoding a Modified Hemagglutinin Trimer of Avian Influenza A Virus H5N8 Protects Mice from Viral Challenge

“…This problem may be solved by the use of modern NFIS. An increase in the immunogenicity of a DNA vaccine administered using NFIS may be associated with a wider distribution of the injected drug within tissues and more efficient delivery into cells [11,14,31]. Moreover, the injection process can act as a physical adjuvant during vaccination [56].…”

“…Vaccines based on nucleic acids do not cause an unwanted anti-vector immune response, which is typical for vaccines based on viral vectors and, therefore, can be administered repeatedly. DNA vaccines are also stable over a wide temperature range [10,11]. So, vaccines based on nucleic acids can be considered as a platform technology that makes it quite easy to replace the target immunogen, without the need to change production [12,13].…”

“…It should also be noted that the DNA vaccine against highly pathogenic influenza A (H5N1) for chicken immunization, developed by Agrilabs, has recently been licensed by the US Department of Agriculture [22]. However, a number of issues related to this platform remain not fully resolved, in particular problems associated with the delivery of a DNA vaccine [11,23,24].…”

mRNA Vaccine for Alzheimer’s Disease: Pilot Study

“…Simultaneously, Martinon et al demonstrated that administration of mice with a mixture of mRNA encoding flu virus nucleoprotein and liposome induced in vaccinated rodents anti-viral T cell responses [ 30 ]. Based on these data, nucleic acid immunization has received considerable scientific interest because of its significant advantages in comparison to conventional vaccines, i.e., ease of manufacturing, high stability, the capability of modifying genes encoding desired antigens, the ability to target cellular localization of an antigen by adding or removing signal sequences or transmembrane domains, and even the ability to elicit the type of immune response [ 31 , 32 , 33 , 34 ]. However, mRNA vaccine technology was halted for many years due to difficulties in manufacturing, the short half-life of mRNA, and its ability to activate the innate immune system.…”

“…In this pilot study, we developed the mRNA counterpart of our MultiTEP-based AV-1959D DNA vaccine using Vernal's proprietary vector for mRNA synthesis (Figure 1A). Specifically, the mRNA encodes the AV-1959 protein, which comprises three copies of the N-terminal region of human Aβ spanning amino acids 1-11, attached to an immunogenic vaccine platform, MultiTEP, consisting of twelve foreign promiscuous T helper (Th) cell epitopes, including one synthetic peptide (PADRE), eight epitopes from Tetanus Toxin (TT) (P2, P21, P23, P30, P32, P7, P17, and P28), two epitopes from HBV surface antigen (HBsAg, aa [19][20][21][22][23][24][25][26][27][28][29][30][31][32][33] and the nucleocapsid (HBVnc, aa 50-69), respectively, and one epitope from influenza virus matrix protein (MT, aa [17][18][19][20][21][22][23][24][25][26][27][28][29][30][31]. The mRNA synthesis involved the incorporation of modified N1-methylPseudoUridine and capping (CAP1) at the 5 ′ end.…”