Tolerability of intramuscular and intradermal delivery by CELLECTRA^®adaptive constant current electroporation device in healthy volunteers

Abstract

DNA vaccines are being developed as a potentially safe and effective immunization platform. However, translation of DNA vaccines into a clinical setting has produced results that have fallen short of those generated in a preclinical setting. Various strategies are being developed to address this lack of potency, including improvements in delivery methods. Electroporation (EP) creates transient increases in cell membrane permeability, thus enhancing DNA uptake and leading to a more robust immune response. Here, we report on the safety and tolerability of delivering sterile saline via intramuscular (IM) or intradermal (ID) injection followed by in vivo electroporation using the CELLECTRA(®) adaptive constant current device in healthy adults from two open-label studies. Pain, as assessed by VAS, was highest immediately after EP but diminishes by about 50% within 5 min. Mean VAS scores appear to correlate with the amount of energy delivered and depth of needle insertion, especially for intramuscular EP. Mean scores did not exceed 7 out of 10 or 3 out of 10 for IM and ID EP, respectively. The majority of adverse events included mild to moderate injection site reactions that resolved within one day. No deaths or serious adverse events were reported during the course of either study. Overall, injection followed by EP with the CELLECTRA(®) device was well-tolerated and no significant safety concerns were identified. These studies support the further development of electroporation as a vaccine delivery method to enhance immunogenicity, particularly for diseases in which traditional vaccination approaches are ineffective.

Skin Transfection Patterns and Expression Kinetics of Electroporation-Enhanced Plasmid Delivery Using the CELLECTRA-3P, a Portable Next-Generation Dermal Electroporation Device

“…The reduced depth of the minimally invasive electrodes has been shown to significantly increase the tolerability of the procedure compared with IM-EP. 29 Because this approach is considered more tolerable, the ability to deliver prophylactic immunizations with minimal invasiveness has become a reality using this device platform.…”

Characterization of guinea pig T cell responses elicited after EP-assisted delivery of DNA vaccines to the skin

“…Upon comparison to naked DNA vaccination, a 10– 100 fold enhancement of the immunological response was observed when EP was employed as an enabling delivery technology [33–35]. While intramuscular (IM) EP has historically been the target tissue of choice, recently, considerable effort has been employed to develop intradermal (ID) EP techniques toward clinical applications [2,4,36,37]. The accessibility of the skin combined with the low penetration depths required for effective drug delivery, result in a less invasive and therefore potentially more tolerable clinical procedure [36,38].…”

“…While intramuscular (IM) EP has historically been the target tissue of choice, recently, considerable effort has been employed to develop intradermal (ID) EP techniques toward clinical applications [2,4,36,37]. The accessibility of the skin combined with the low penetration depths required for effective drug delivery, result in a less invasive and therefore potentially more tolerable clinical procedure [36,38]. The high number of resident professional antigen presenting cell populations endow the skin with very attractive characteristics for a target tissue for vaccine delivery.…”

Technologies to Improve Immunization

“…Acceptability is a challenge, particularly for IM electroporation devices, although ID devices have been found to be more tolerable. 395 The cost and complexity of the devices could preclude use in most low-resource settings.…”