Enhanced Delivery and Potency of Self-Amplifying mRNA Vaccines by Electroporation in Situ.
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.
Novartis Vaccines & Diagnostics, Inc., 350 Massachusetts Ave, Cambridge, MA 02139, USA.
Yen
Y
Cu
Inovio Pharmaceuticals, Blue Bell, PA 19422, USA.
Kate E
KE
Broderick
Novartis Vaccines & Diagnostics, Inc., 350 Massachusetts Ave, Cambridge, MA 02139, USA.
Kaustuv
K
Banerjee
Novartis Vaccines & Diagnostics, Inc., 350 Massachusetts Ave, Cambridge, MA 02139, USA.
Julie
J
Hickman
Novartis Vaccines & Diagnostics, Inc., 350 Massachusetts Ave, Cambridge, MA 02139, USA.
Gillis
G
Otten
Novartis Vaccines & Diagnostics, Inc., 350 Massachusetts Ave, Cambridge, MA 02139, USA.
Susan
S
Barnett
Inovio Pharmaceuticals, Blue Bell, PA 19422, USA.
Gleb
G
Kichaev
Inovio Pharmaceuticals, Blue Bell, PA 19422, USA.
Niranjan Y
NY
Sardesai
Novartis Vaccines & Diagnostics, Inc., 350 Massachusetts Ave, Cambridge, MA 02139, USA.
Jeffrey B
JB
Ulmer
Novartis Vaccines & Diagnostics, Inc., 350 Massachusetts Ave, Cambridge, MA 02139, USA. andrew.geall@novartis.com.
Andrew
A
Geall
HIV; T cell responses; antibodies; vaccine