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Vaccines 2013, 1(3), 367-383; doi:10.3390/vaccines1030367

Enhanced Delivery and Potency of Self-Amplifying mRNA Vaccines by Electroporation in Situ

1,†, 2, 1, 1, 1, 1, 2, 2, 1 and 1,*
1 Novartis Vaccines & Diagnostics, Inc., 350 Massachusetts Ave, Cambridge, MA 02139, USA 2 Inovio Pharmaceuticals, Blue Bell, PA 19422, USA Present address: Kala Pharmaceuticals Inc., Waltham, MA 02452, USA.
* Author to whom correspondence should be addressed.
Received: 26 June 2013 / Revised: 12 August 2013 / Accepted: 14 August 2013 / Published: 22 August 2013
(This article belongs to the Special Issue DNA Vaccines)
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Nucleic acid-based vaccines such as viral vectors, plasmid DNA (pDNA), and mRNA are being developed as a means to address limitations of both live-attenuated and subunit vaccines. DNA vaccines have been shown to be potent in a wide variety of animal species and several products are now licensed for commercial veterinary but not human use. Electroporation delivery technologies have been shown to improve the generation of T and B cell responses from synthetic DNA vaccines in many animal species and now in humans. However, parallel RNA approaches have lagged due to potential issues of potency and production. Many of the obstacles to mRNA vaccine development have recently been addressed, resulting in a revival in the use of non-amplifying and self-amplifying mRNA for vaccine and gene therapy applications. In this paper, we explore the utility of EP for the in vivo delivery of large, self-amplifying mRNA, as measured by reporter gene expression and immunogenicity of genes encoding HIV envelope protein. These studies demonstrated that EP delivery of self-amplifying mRNA elicited strong and broad immune responses in mice, which were comparable to those induced by EP delivery of pDNA.
Keywords: antibodies; T cell responses; vaccine; HIV antibodies; T cell responses; vaccine; HIV
This is an open access article distributed under the Creative Commons Attribution License (CC BY) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Cu, Y.; Broderick, K.E.; Banerjee, K.; Hickman, J.; Otten, G.; Barnett, S.; Kichaev, G.; Sardesai, N.Y.; Ulmer, J.B.; Geall, A. Enhanced Delivery and Potency of Self-Amplifying mRNA Vaccines by Electroporation in Situ . Vaccines 2013, 1, 367-383.

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