Synthetic DNA Vaccines: Improved Vaccine Potency by Electroporation and Co-Delivered Genetic Adjuvants

Abstract

In recent years, DNA vaccines have undergone a number of technological advancements that have incited renewed interest and heightened promise in the field. Two such improvements are the use of genetically engineered cytokine adjuvants and plasmid delivery via in vivo electroporation (EP), the latter of which has been shown to increase antigen delivery by nearly 1000-fold compared to naked DNA plasmid delivery alone. Both strategies, either separately or in combination, have been shown to augment cellular and humoral immune responses in not only mice, but also in large animal models. These promising results, coupled with recent clinical trials that have shown enhanced immune responses in humans, highlight the bright prospects for DNA vaccines to address many human diseases.

Coadministration of a Plasmid Encoding HIV-1 Gag Enhances the Efficacy of Cancer DNA Vaccines

“…Indeed, EP of a pDNA led to the induction of type I IFNs in vivo, whereas EP without pDNA or injection of pDNA without EP did not strongly induce the IFN-β promoter (Figure 2). An explanation of this phenomenon may be an increase in DNA plasmid transfection 7 and thus a higher sensing of aberrant cytosolic DNA. In most cases, the recognition of cytosolic DNA results in the induction of the innate immune response through the STING-TBK1 signaling cascade, and thus the subsequent expression of type I IFNs.…”

“…33 In contrast, the use of plasmid encoding immunomodulatory proteins permits the coordinated delivery of antigens and adjuvants, tailoring the immune response to the demands of each particular disease. 7 Until now, most of the genetic adjuvants used in trials encode proteins that activate innate immune responses directly, such as cytokines, chemokines, signaling or costimulatory molecules. Here, the strategy is different and innovative as pGag most likely induces innate immune responses indirectly, through PAMP recognition by pattern recognition receptors.…”

“…6,8 This method was used to improve DNA vaccine efficacy in large animals. 7,9 EP efficiency is not only attributed to an enhanced gene transfer 7 but also to the induction of a transient tissue inflammation and the subsequent local recruitment of immune cells. 1,10 Second, genetic adjuvants, i.e., plasmid vectors encoding immunomodulatory molecules, aim at enhancing the immunogenicity of antigens in vivo.…”

“…11 These genetic adjuvants include cytokines, chemokines, or immune stimulatory molecules, such as toll-like receptor (TLR) agonists or interferon (IFN) regulatory factors. 7,[12][13][14] Most of these adjuvants are used in preclinical studies, and even though they are promising, only a few of them have been evaluated in clinical trials until now. Therefore, there is still a critical need of clinically applicable genetic adjuvants.…”

“…6 Particularly, plasmid delivery by in vivo electroporation (EP) and the use of genetically encoded immune adjuvants have enhanced DNA vaccine efficacy. 7 First, EP is the most commonly used and the most powerful nonviral delivery method for DNA vaccines. 6,8 This method was used to improve DNA vaccine efficacy in large animals.…”