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 multihead 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.

A Rift Valley fever virus Gn ectodomain-based DNA vaccine induces a partial protection not improved by APC targeting

“…Indeed, for application in the field and especially in Africa, the minimum number of administrations and the plasmid dose to achieve protection should be established with downscaling experiments, and the mode of delivery should be adapted to mass vaccination, such as with a high pressure needle-free delivery system which has been shown to be as efficient as electroporation in pigs 16 or possibly with new portable electroporation-based systems. 53 The level of protection that we achieved is incomplete and complete immunity is desirable to protect the highly sensitive fetuses; however, a strong decrease in viral load would also decrease the risk of transmission to mosquito vectors. The immunity triggered by peGn might be further improved by adding other RVFV antigens such as by adding Gc (or eGc) and/or N proteins.…”

Adipose tissue: a new target for electroporation-enhanced DNA vaccines

“…The authors do not believe this to be a clinical hurdle as designing a device that targets multiple sites simultaneously has been previously tested by this group for skin vaccination. 40 …”

Technologies to Improve Immunization

“…Noninvasive surface electroporation devices have also been developed by Inovio and may have better acceptability. 392 The Easy Vax and related Derma Vax epidermal electroporation systems combine the application of antigen-or drug-delivery offer the advantage of speed, simplicity, and patient acceptability as well as the ability to use off-the-shelf vaccines without reformulation. Challenges include developing devices that reliably deliver small ID doses to the correct depth, 266,269 obtaining clinical data to license vaccines for ID delivery by DSJIs, and the higher cost of DSJI devices compared with an ID needles and syringes.…”