Chapter 3

Delivery of DNA-Based Vaccines with In Vivo Electroporation

Trevor R.F. Smith, Katherine Schultheis and Kate E. Broderick

Abstract

Recent technological advances have re-established the value of DNA-based vaccines in tackling unmet medical needs. Such advances include the optimization of DNA plasmid constructs, the addition of novel molecular adjuvants into the formulations, and the development of in vivo delivery strategies such as electroporation (EP). The combination of DNA-based vaccines with the delivery platform of EP has enhanced the antigen expression by up to 1000-fold higher than DNA injection alone, resulting in greatly enhanced immunogenicity of DNA-based vaccines. Pre-clinical EPenhanced DNA-based vaccination has elicited robust functional host immune responses to a myriad of disease targets resulting in protection from viral challenge or tumor growth, depending on the disease model. Significantly, the problems encountered in translating these responses to the clinic have been overcome, and equally impressive immune responses are being observed in human beings when DNA-based vaccination is married with EP, as was observed in a recent clinical trial. In this review we will cover the principles of EP in respect to enhancing DNA-based vaccination protocols targeting pDNA delivery to the muscle or skin, and discuss the top line results that have revealed for the first time clinical efficacy of DNA-based vaccine candidates.

Total Pages: 68-100 (33)

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