A multi-head intradermal electroporation device allows for tailored and increased dose DNA vaccine delivery to the skin

Abstract

The identification of an effective and tolerable delivery method is a necessity for the success of DNA vaccines in the clinic. This article describes the development and validation of a multi-headed intradermal electroporation device which would be applicable for delivering multiple DNA vaccine plasmids simultaneously but spatially separated. Reporter gene plasmids expressing green and red fluorescent proteins were used to demonstrate the impact of spatial separation on DNA delivery to increase the number of transfected cells and avoid interference through visible expression patterns. To investigate the impact of plasmid interference on immunogenicity, a disease target was investigated where issues with multi-valent vaccines had been previously described. DNA-based Hantaan and Puumala virus vaccines were delivered separately or as a combination and the effect of multi-valence was determined by appropriate assays. While a negative impact was observed for both antigenic vaccines when delivered together, these effects were mitigated when the vaccine was delivered using the multi-head device. We also demonstrate how the multi-head device facilitates higher dose delivery to the skin resulting in improved immune responses. This new multi-head platform device is an efficient, tolerable and non-invasive method to deliver multiple plasmid DNA constructs simultaneously allowing the tailoring of delivery sites for combination vaccines. Additionally, this device would allow the delivery of multi-plasmid vaccine formulations without risk of impacted immune responses through interference. Such a low-cost, easy to use device platform for the delivery of multi-agent DNA vaccines would have direct applications by the military and healthcare sectors for mass vaccination purposes.

Keywords:

• dermal
• DNA vaccine
• electroporation
• multi-agent
• noninvasive
• tolerable

Disclosure of Potential Conflicts of Interest

K.E.B., N.Y.S., J.B.M., A.G., and J.M.M. are employees of Inovio Pharmaceuticals and as such receive compensation in the form of salary, stock options and bonuses. C.S.S., K.W.S., and C.B. are employees of the US government and so do not declare any conflicts.

Acknowledgments

We would like to thank Maria Yang and Sayed Sadat for plasmid preparation and Katherine Schultheis for manuscript preparation assistance.

Funding

This work was supported in part by a Department of Defense SBIR grant (Phase I and Phase II) number W81XWH-11-C-0051.