Abstract
DNA vaccines still represent an emergent area of research, giving rise to continuous progress towards several biomedicine demands. The formulation of delivery systems to specifically target mannose receptors, which are overexpressed on antigen presenting cells (APCs), is considered a suitable strategy to improve the DNA vaccine immunogenicity. The present study developed binary and ternary carriers, based on polyethylenimine (PEI), octa-arginine peptide (R8), and mannose ligands, to specifically deliver a minicircle DNA (mcDNA) vaccine to APCs. Systems were prepared at various nitrogen to phosphate group (N/P) ratios and characterized in terms of their morphology, size, surface charge, and complexation capacity. In vitro studies were conducted to assess the biocompatibility, cell internalization ability, and gene expression of formulated carriers. The high charge density and condensing capacity of both PEI and R8 enhance the interaction with the mcDNA, leading to the formation of smaller particles. The addition of PEI polymer to the R8-mannose/mcDNA binary system reduces the size and increases the zeta potential and system stability. Confocal microscopy studies confirmed intracellular localization of targeting systems, resulting in sustained mcDNA uptake. Furthermore, the efficiency of in vitro transfection can be influenced by the presence of R8-mannose, with great implications for gene expression. R8-mannose/PEI/mcDNA ternary systems can be considered valuable tools to instigate further research, aiming for advances in the DNA vaccine field.
Highlights
DNA vaccines still represent an emergent area of research, giving rise to continuous progress towards several biomedicine demands
The results showed that genomic DNA eluted mostly in the first peak, parental plasmid (PP) eluted mostly in the second peak, minicircle DNA (mcDNA) molecules eluted mostly in the third peak
The main challenge associated with DNA vaccines and its main limitation for clinical application is the delivery barriers to targeted immune cells, which obstruct the stimulation of effective antigen-specific immune responses in humans, which leads to low therapeutic efficacy
Summary
DNA vaccines still represent an emergent area of research, giving rise to continuous progress towards several biomedicine demands. The formulation of delivery systems to target mannose receptors, which are overexpressed on antigen presenting cells (APCs), is considered a suitable strategy to improve the DNA vaccine immunogenicity. The present study developed binary and ternary carriers, based on polyethylenimine (PEI), octa-arginine peptide (R8), and mannose ligands, to deliver a minicircle DNA (mcDNA) vaccine to APCs. Systems were prepared at various nitrogen to phosphate group (N/P) ratios and characterized in terms of their morphology, size, surface charge, and complexation capacity. Prophylactic HPV vaccination is currently the best strategy for preventing cervical cancer, this type of vaccine induces only humoral immunity (producing neutralizing antibodies) to prevent future infections, it is not effective in treating pre-existing infections In this context, DNA vaccines have particular importance due to their ability to generate cellular and humoral immune responses, based on the use of genetic material sequences from the pathogen that is intended to be fought [4]. E6 and E7 viral oncoproteins are suitable targets for the formulation of therapeutic vaccines, since they are overexpressed in HPV-infected cells at early stages [1]
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