Abstract
DNA vaccination can be applied to the treatment of various infectious diseases and cancers; however, technical difficulties have hindered the development of an effective delivery method. The efficacy of a DNA vaccine depends on optimal antigen expression by the injected plasmid DNA. The pyro-drive jet injector (PJI) is a novel system that allows for adjustment of injection depth and may, thus, provide a targeted delivery approach for various therapeutic or preventative compounds. Herein, we investigated its potential for use in delivering DNA vaccines. This study evaluated the optimal ignition powder dosage, as well as its delivery effectiveness in both rat and mouse models, while comparing the results of the PJI with that of a needle syringe delivery system. We found that the PJI effectively delivered plasmid DNA to intradermal regions in both rats and mice. Further, it efficiently transfected plasmid DNA directly into the nuclei, resulting in higher protein expression than that achieved via needle syringe injection. Moreover, results from animal ovalbumin (OVA) antigen induction models revealed that animals receiving OVA expression plasmids (pOVA) via PJI exhibited dose-dependent (10 μg, 60 μg, and 120 μg) production of anti-OVA antibodies; while only low titers (< 1/100) of OVA antibodies were detected when 120 μg of pOVA was injected via needle syringe. Thus, PJI is an effective, novel method for delivery of plasmid DNA into epidermal and dermal cells suggesting its promise as a tool for DNA vaccination.
Highlights
Technology is constantly changing and advancing with many novel devices being discovered with potential to serve as preventative or therapeutic strategies for various diseases
By comparing plasmid DNA delivery between needle syringe and pyro-drive jet injector (PJI), we found that the PJI group exhibited evenly distributed Cy3-labeled plasmid DNA (Cy3-p) in the epidermal and dermal regions, whereas needle syringe injection primarily resulted in plasmid DNA distribution in the dermal to subcutaneous regions (Fig. 2a, b)
Results from the Cy3-p induction study showed that PJI resulted in more efficient plasmid DNA distribution to the nucleus compared to that with the needle syringe
Summary
Technology is constantly changing and advancing with many novel devices being discovered with potential to serve as preventative or therapeutic strategies for various diseases. For more than two centuries, vaccination has been widely employed as an effective medical technology. Considering the initial immune stimulation induced by vaccines, the distribution of antigen-presenting cells (APCs) is considered an important element for vaccine effectiveness. Since APCs function to process the antigen, present epitopes on the cell surface, and stimulate other immune cells, including T lymphocytes, their induction is considered a primary and essential step for effective immunization. The intradermal region is considered to be an optimal target for vaccine delivery due to ease of access for APCs such as Langerhans’s cells (LH cells) and dermal dendritic cells within this region. Intradermal injection is technically difficult for non-professionals to perform; to overcome this obstacle, needleless injection systems, such as the micro-needle or jet injector, have been developed and employed [2,3,4]
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