Abstract
DNA vaccines delivered using electroporation (EP) have had clinical success, but these EP methods generally utilize invasive needle electrodes. Here, we demonstrate the delivery and immunogenicity of a DNA vaccine into subcutaneous adipose tissue cells using noninvasive EP. Using finite element analysis, we predicted that plate electrodes, when oriented properly, could effectively concentrate the electric field within adipose tissue. In practice, these electrodes generated widespread gene expression persisting for at least 60 days in vivo within interscapular subcutaneous fat pads of guinea pigs. We then applied this adipose-EP protocol to deliver a DNA vaccine coding for an influenza antigen into guinea pigs. The resulting host immune responses elicited were of a similar magnitude to those achieved by skin delivery with EP. The onset of the humoral immune response was more rapid when the DNA dose was spread over multiple injection sites, and increasing the voltage of the EP device increased the magnitude of the immune response. This study supports further development of EP protocols delivering gene-based therapies to subcutaneous fat.
Highlights
The delivery of DNA-encoded vaccine antigens is a promising vaccination strategy that offers several advantages over traditional vaccine methods
There is no vector-acquired immunity. This permits repeated administrations of plasmid DNA vaccines to boost immunity, without the requirement to re-engineer the construct for each vaccine
In a bid to understand the electrical properties of adipose tissue from an EP perspective, finite element analysis was carried out to quantify the predicted electric field distribution within each tissue type of interest using the two electrode designs—needles within flat tissue and plates around folded tissue—illustrated in Figure 1, using a 200 V excitation in both cases
Summary
The delivery of DNA-encoded vaccine antigens is a promising vaccination strategy that offers several advantages over traditional vaccine methods. This permits repeated administrations of plasmid DNA vaccines to boost immunity, without the requirement to re-engineer the construct for each vaccine. Before the employment of electroporation (EP) as an enabling technology, the success of DNA vaccines has historically been limited because transfection efficiency is poor following simple injection of naked DNA Overcoming this barrier by increasing the dose is impractical when scaling up to larger animals and humans, and several clinical trials in the past utilizing protocols based on injection of naked plasmid DNA failed to replicate the promising preclinical data.[1,2,3] To overcome these delivery limitations, the physical application of EP has been established as a key enabling technology for the in vivo delivery of plasmid DNA vectors for vaccination
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