Abstract
Current progress in the development of vaccines has decreased the incidence of fatal and non-fatal infections and increased longevity. However, new technologies need to be developed to combat an emerging generation of infectious diseases. DNA vaccination has been demonstrated to have great potential for use with a wide variety of diseases. Alone, this technology does not generate a significant immune response for vaccination, but combined with delivery by electroporation (EP), can enhance plasmid expression and immunity. Most EP systems, while effective, can be invasive and painful making them less desirable for use in vaccination. Our lab recently developed a non-invasive electrode known as the multi-electrode array (MEA), which lies flat on the surface of the skin without penetrating the tissue. In this study we evaluated the MEA for its use in DNA vaccination using Hepatitis B virus as the infectious model. We utilized the guinea pig model because their skin is similar in thickness and morphology to humans. The plasmid encoding Hepatitis B surface antigen (HBsAg) was delivered intradermally with the MEA to guinea pig skin. The results show increased protein expression resulting from plasmid delivery using the MEA as compared to injection alone. Within 48 hours of treatment, there was an influx of cellular infiltrate in experimental groups. Humoral responses were also increased significantly in both duration and intensity as compared to injection only groups. While this electrode requires further study, our results suggest that the MEA has potential for use in electrically mediated intradermal DNA vaccination.
Highlights
The development of vaccines is widely considered to be one of the most important medical advancements of the 20th century
Expression of Hepatitis B surface antigen (HBsAg) is seen in injection only (IO) and I+EP (Fig. 1a and b), increased staining was observed in the I+EP samples
The fold increase over IO remained relatively constant at about 5 fold with the greatest fold increase over IO of 6.5 occurring at week 18. These data demonstrate that the multi-electrode array (MEA) can be effective for the use in electrically mediated DNA vaccination in a human-like skin model
Summary
The development of vaccines is widely considered to be one of the most important medical advancements of the 20th century. There are several advantages to DNA vaccination. DNA vaccines are cost effective to produce, they can be stored, they are highly specific and their multivalent nature means that they could be combined to vaccinate against several different components simultaneously [1,2,3]. Either due to low expression or lack of immune recognition, injection of plasmid DNA alone does not elicit a strong enough immune response for protective vaccination. Electroporation (EP) is a non viral plasmid DNA delivery approach that effectively enhances plasmid expression [4,5] and immunity [6,7,8,9,10]
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