Electroporation delivery of DNA vaccines: prospects for success

Abstract

Summary A number of noteworthy technology advances in DNA vaccines research and development over the past few years have led to the resurgence of this field as a viable vaccine modality. Notably, these include - optimization of DNA constructs; development of new DNA manufacturing processes and formulations; augmentation of immune responses with novel encoded molecular adjuvants; and the improvement in new in vivo delivery strategies including electroporation (EP). Of these, EP mediated delivery has generated considerable enthusiasm and appears to have had a great impact in vaccine immunegenicity and efficacy by increasing antigen delivery upto a 1000 fold over naked DNA delivery alone. This increased delivery has resulted in an improved in vivo immune response magnitude as well as response rates relative to DNA delivery by direct injection alone. Indeed the immune responses and protection from pathogen challenge observed following DNA administration via EP in many cases are comparable or superior to other well studied vaccine platforms including viral vectors and live/attenuated/inactivated virus vaccines. Significantly, the early promise of EP delivery shown in numerous pre-clinical animal models of many different infectious diseases and cancer are now translating into equally enhanced immune responses in human clinical trials making the prospects for this vaccine approach to impact diverse disease targets tangible.

Nonviral delivery of self-amplifying RNA vaccines

“…For pDNA the immune responses in larger species have been generally lower than in small animals, with the amount of pDNA required for effective immunization of larger animals being 1,000-fold higher than for small species (milligrams versus micrograms) (2). The current costs of clinical manufacturing of pDNA are on the order of $50-100 per milligram (1-10 g scale) (26). The current projection for the cost of mRNA manufacture is comparable (9), which makes a very compelling commercial case for extensive evaluation of nonviral delivery of self-amplifying RNA and testing in larger animal species.…”

“…These single-cycle alphavirus vectors were used as the viral delivery benchmark in our studies. Similarly, EP-mediated delivery of pDNA has been shown to be broadly effective (26) and thus was used as the benchmark for pDNA delivery.…”

Dissolving microneedles for DNA vaccination: Improving functionality via polymer characterization and RALA complexation

“…DNA vaccines rely on the delivery of antigen-coding DNA to the nucleus of cells, but due to the large molecular weight, anionic charge and susceptibility of DNA to enzymatic degradation physical injection of DNA often results in very low transfection efficacies. 3 Physical methods of disrupting the cell membrane such as electroporation 4 and ballistic delivery 5 have been demonstrated to enhance gene expression levels significantly in vivo. However these devices are associated with pain, 6,7 and require the use of expensive specialist equipment, making them less acceptable to patients and unsuitable for mass vaccination.…”

Non-contact helium-based plasma for delivery of DNA vaccines

“…3 Generation of optimized DNA expression plasmids, as well as development of delivery enhancement methods, have been evaluated as methods to increase the efficacy of DNA vaccines. [4][5][6][7] Electroporation (EP) is among a number of delivery enhancement modalities evaluated in recent years. This electric pulsebased delivery method has been successful in increasing expression and enhancing immune responses against proteins generated by DNA.…”