Abstract
Recently newer synthetic DNA vaccines have been rapidly advanced to clinical study and have demonstrated an impressive degree of immune potency and tolerability. Improvements in DNA delivery over prior needle and syringe approaches include jet delivery, gene gun delivery, among others. Among the most effective of these new delivery methods, advanced electroporation (EP), combined with other advances, induces robust humoral and cellular immunity in both preventative as well as therapeutic studies. Advancements in the design of the DNA inserts include leader sequence changes, RNA and codon optimizations, improved insert designs, increased concentrations of DNA, and skin delivery, appear to complement newer delivery strategies. These advances also provide a framework for the in vivo production of synthetic DNA biologics. In this review, we focus on recent studies of synthetic DNA vaccines in the clinic for the prevention or treatment of infectious diseases with a focus on adaptive electroporation for delivery, and briefly summarize novel preclinical data advancing the in vivo delivery of DNA-encoded antibody-like biologics.
Highlights
Vaccines are among the most important medical interventions in human history
Transfected antigen-presenting cells (APCs) can directly traffic to the regional lymph node (LN) which is critical to initiating the immune response [5,6]
DNA vaccination and immunotherapy. (a) DNA-encoded antigens are transcribed, translated, and presented on major histocompatibility complex-1 (MHC I) and II molecules in vivo, promoting robust anti-target immunity. (b) The 1000X increase in DNA delivery coupled with highly efficient encoded antigen production allow this local delivery to become a source for production of biologics
Summary
Vaccines are among the most important medical interventions in human history. We are in an era of unprecedented scientific advance in vaccine technologies. Intramuscular (IM) inoculation and more recently intradermal (ID) delivery using highly concentrated formulations have induced consistent immunity in the clinic Delivery methods such as jet delivery, gene gun delivery, nanoparticle delivery, and others have demonstrated increased DNA uptake in vivo [1]. Adaptive EP increases the initial uptake of plasmid by local cells approximately 500x [3]. This creates a large antigen bolus to drive a more potent immune response. Transfected antigen-presenting cells (APCs) can directly traffic to the regional lymph node (LN) which is critical to initiating the immune response [5,6]. Since the 900s DNA plasmids have been www.sciencedirect.com
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