The next-generation DNA vaccine platforms and delivery systems: advances, challenges and prospects

Abstract

Vaccines have proven effective in the treatment and prevention of numerous diseases. However, traditional attenuated and inactivated vaccines suffer from certain drawbacks such as complex preparation, limited efficacy, potential risks and others. These limitations restrict their widespread use, especially in the face of an increasingly diverse range of diseases. With the ongoing advancements in genetic engineering vaccines, DNA vaccines have emerged as a highly promising approach in the treatment of both genetic diseases and acquired diseases. While several DNA vaccines have demonstrated substantial success in animal models of diseases, certain challenges need to be addressed before application in human subjects. The primary obstacle lies in the absence of an optimal delivery system, which significantly hampers the immunogenicity of DNA vaccines. We conduct a comprehensive analysis of the current status and limitations of DNA vaccines by focusing on both viral and non-viral DNA delivery systems, as they play crucial roles in the exploration of novel DNA vaccines. We provide an evaluation of their strengths and weaknesses based on our critical assessment. Additionally, the review summarizes the most recent advancements and breakthroughs in pre-clinical and clinical studies, highlighting the need for further clinical trials in this rapidly evolving field.

Advances in Nucleic Acid Universal Influenza Vaccines

“…Genome insertion could be controlled with modified DNA sequences and their low immunogenicity in humans could be improved with several strategies [ 41 ]. Given these advantages, influenza DNA vaccines have the potential to provide a broader protection as universal vaccines with the characteristics of easy preparation, simplicity of formulation, high stability and safety by lacking infectious regents [ 60 ].…”

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.…”

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

“…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].…”