DNA vaccines: prime time is now

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.

Figure 1

DNA vaccination and immunotherapy. (a) DNA-encoded antigens are transcribed, translated, and presented on 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. Inserts are highly designed to allow for local expression. Multiple publications have now described how DNA-encoded monoclonal antibodies (DMAbs), bispecific antibodies, and immunogens can be used to target cancer or infectious diseases.

Figure 2

Selected Recent DNA vaccines in the clinic. All the reported constructs were found to be safe and immunogenic in the clinic. Several of these have reported clinical impact or outcomes representing important immune readouts.