Abstract
There is a growing demand for better delivery systems to improve the stability and efficacy of DNA vaccines. Here we report the synthesis of a non-viral DNA vaccine delivery system using a novel adjuvanted solid lipid nanoparticle (SLN-A) platform as a carrier for a DNA vaccine candidate encoding the Urease alpha (UreA) antigen from Helicobacter pylori. Cationic SLN-A particles containing monophosphoryl lipid A (adjuvant) were synthesised by a modified solvent-emulsification method and were investigated for their morphology, zeta potential and in vitro transfection capacity. Particles were found to bind plasmid DNA to form lipoplexes, which were characterised by electron microscopy, dynamic light scattering and fluorescence microscopy. Cellular uptake studies confirmed particle uptake within 3 h, and intracellular localisation within endosomal compartments. In vitro studies further confirmed the ability of SLN-A particles to stimulate expression of pro-inflammatory cytokine tumor necrosis factor alpha (TNF-α) in human macrophage-like Tohoku Hospital Pediatrics-1 (THP-1) cells. Lipoplexes were found to be biocompatible and could be efficiently transfected in murine immune cells for expression of recombinant H. pylori antigen Urease A, demonstrating their potential as a DNA vaccine delivery system.
Highlights
Compared to traditional approaches to vaccination, DNA vaccines offer a safe, inexpensive and scalable alternative to inducing antigen-specific immune responses [1]
This study demonstrates the application of solid lipid nanoparticle (SLN-A) nanoparticles as a nanocarrier system for a DNA vaccine encoding the H. pylori antigen urease alpha
Solid lipid nanoparticles were successfully synthesised by a modified solvent-emulsification method [16] adapted to include the addition of adjuvant lipid Monophosphoryl lipid A (MPL-A), producing novel adjuvanted
Summary
Compared to traditional approaches to vaccination, DNA vaccines offer a safe, inexpensive and scalable alternative to inducing antigen-specific immune responses [1]. DNA vaccines are a relatively modern approach, in which a plasmid encoding an antigen is expressed by the host in order to generate a protective immune response. 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 delivery systems are being increasingly applied to improve the efficacy of DNA vaccines. The linking of DNA to a particulate carrier has been demonstrated to improve DNA vaccine uptake, expression and immune priming [1].
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