Engineered Nanodelivery Systems to Improve DNA Vaccine Technologies

Abstract

DNA vaccines offer a flexible and versatile platform to treat innumerable diseases due to the ease of manipulating vaccine targets simply by altering the gene sequences encoded in the plasmid DNA delivered. The DNA vaccines elicit potent humoral and cell-mediated responses and provide a promising method for treating rapidly mutating and evasive diseases such as cancer and human immunodeficiency viruses. Although this vaccine technology has been available for decades, there is no DNA vaccine that has been used in bed-side application to date. The main challenge that hinders the progress of DNA vaccines and limits their clinical application is the delivery hurdles to targeted immune cells, which obstructs the stimulation of robust antigen-specific immune responses in humans. In this updated review, we discuss various nanodelivery systems that improve DNA vaccine technologies to enhance the immunological response against target diseases. We also provide possible perspectives on how we can bring this exciting vaccine technology to bedside applications.

COVID-19 vaccine development and a potential nanomaterial path forward

“…Nanotechnology-based approaches offer enabling solutions to the delivery challenge by trafficking the vaccine to appropriate cellular populations and subcellular locations. While synthetic nanocarriers including cationic liposomes and polymeric nanoparticles have been used for the delivery of DNA vaccines across cell membranes, targeted formulations could further enhance nuclear translocation of the plasmid DNA 47 . Moderna's mRNA vaccine is based on a lipid nanoparticle platform, but there are many other emerging nanotechnologies for delivery of nucleic acid vaccines (several structures are shown in Fig.…”

COVID-19: Current Developments and Further Opportunities in Drug Delivery and Therapeutics

“…Contrary to most subunit vaccines, the ability of nucleic acid vaccines to elicit both the cellular and humoral immune responses make them promising vaccine candidates, although traditional attenuated vaccines are also capable of inducing both arms (cellular and humoral) of immune response; however, the possibility of reversion from the attenuated to the virulent state remains a limitation of this approach [ 122 ]. Delivery of nucleic acid vaccines by encapsulation in the polymeric or lipid matrices/nanoparticles and with the help of adjuvants has been successfully studied in order to circumvent different challenges such as the harsh digestive tract environment, enzymatic degradation and difficulty in crossing the phospholipid membrane (negatively charged) [ 123 , 124 , 125 ]. Chemical modification of RNA by pseudouridine can significantly enhance protein generation in-vivo by circumventing the protein translation inhibition, which is triggered by unmodified nucleotides [ 126 ].…”

Solid Lipid Nanoparticle Carrier Platform Containing Synthetic TLR4 Agonist Mediates Non-Viral DNA Vaccine Delivery

“…DNA vaccines are considered safer than live-attenuated or whole pathogen vaccines due to their inability to cause disease. Despite their excellent safety profile, DNA-based formulations often lack immunogenicity and suffer rapid nuclease degradation and phagocytic elimination by the reticulo-endothelial system [2].…”

“…Nanoparticle-based nucleic acid delivery platforms based on metals such as gold and silver, and metal oxides such as silica and iron oxide, have been demonstrated to offer advantages over traditional soluble antigen vaccines [5,6]. Nanoparticle vaccine formulations can protect antigens from degradation resulting in greater immunological priming and improved immunological outcomes, as well as having adjuvant-like stimulatory properties themselves [2,3]. Some disadvantages of particulate carrier systems include poor clearance and the induction of non-specific inflammation which can interfere with adaptive immune responses [7].…”