Delivery of DNA-Based Vaccines with In Vivo Electroporation
Pp. 68-100 (33)
Trevor R.F. Smith, Katherine Schultheis and Kate E. Broderick
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.
DNA-based vaccines, Electroporation.
Inovio Pharmaceuticals, Inc., 660W. Germantown Pike, Suite 110, Plymouth Meeting, PA 19462, USA.