Stable Immune Response Induced by Intradermal DNA Vaccination by a Novel Needleless Pyro-Drive Jet Injector

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.Electronic supplementary materialThe online version of this article (10.1208/s12249-019-1564-z) contains supplementary material, which is available to authorized users.

Vaccination into the Dermal Compartment: Techniques, Challenges, and Prospects

“…A range of other devices have been developed and trialled in recent years. For instance, Genetronics Inc (San Diego, CA, USA) patented an injector pen, which uses a spring mechanism to apply needle-free intradermal injection of a liquid [ 176 ]. The Injex30 provided comparable antibody titres to subcutaneous N&S injection in a study with mice vaccinated against hepatitis B surface antigen [ 163 ].…”

Potent Intradermal Gene Expression of Naked Plasmid DNA in Pig Skin Following Pyro-drive Jet Injection

“…Our previous studies have shown that the novel jet injector driven by explosives, called pyro-drive jet injector, was efficient for ID administration in rats and mice, leading to efficient expression of transgenes. 8 However, the immune response and the significance of pyro-drive jet injections following DNA vaccination in large animals seem to be unclear, as jet injectors adjusted for ID administration have not been used in the previous studies. In the present study, we evaluated the application of jet injection for gene transfer via ID injection compared with that of needle syringes, using pig skin as a morphological model that mimics human skin in a translational research.…”

“…6,7 The injection was efficient in promoting gene transfer, antigen expression, and immune responses in mouse and rat models. [5][6][7][8] However, although the studies using jet injection with small animals are promising, similar results are not always obtained in humans.…”

Vaccine formulations in clinical development for the prevention of severe acute respiratory syndrome coronavirus 2 infection

“…While publicly available information on the antigen and adjuvant is unavailable, it is evident that they are employing plasmid DNA delivered by a pyro-drive jet injector (PJI), which employs the detonation of small amounts of explosive powder to propel plasmids in a jet into the skin at variable, controllable depths [ 119 ]. In a preclinical evaluation of this technology to vaccinate against the model antigen ovalbumin in mice and rats, they demonstrated that plasmid DNA delivered by PJI induced significantly greater antigen expression and resultant antibody titers compared to needle-injected plasmid DNA [ 120 ]. This technology presents the advantage of needle-free, single step delivery with the potential to optimize the depth of delivery to induce the optimal immune response.…”

“…Curevac has announced that they will begin Phase 1/2a clinical trials in June of 2020 for a SARS-CoV-2 vaccine, with this vaccine utilizing the same lipid formulation as Pfizer/BioNtech with mRNA encoding S protein of the virus [ 58 , 143 , 144 ]. This change from a protamine based carrier to a lipid based particle may be due to the fact that LNPs are shown to work better when given via standard intramuscular injection [ 145 ], whereas the protamine based formulation only induced neutralizing titers when administered with less common needle-free injection mechanisms similar to those used in previous studies of DNA vaccination [ 58 , 120 ]. Another consideration might be the enhanced storage they announced with their new LNP formulation, noting that they have a formulation suitable for storage at three months at standard refrigeration temperature (5 °C) [ 146 ].…”