Thursday, August 29, 2013 4:23:32 PM
Sep 4, 2012
abstract-Nonviral delivery of self-amplifying RNA vaccines
Andrew J. Geall Novartis Vaccines
ACKNOWLEDGMENTS
We thank the RNA Vaccine Platform Team at Novartis Vaccines and Diagnostics and, in particular, Jacob Archer, Mithra Rothfeder, and Avishek Nandi for their assistance in producing the RNA and DNA for these studies; Michelle Chan for coordinating the delivery of formulations for the animal studies; Alison Curtis and Melissa Sackal for their assistance in conducting the bioluminescence studies in mice; Christine Dong Lee for conducting the RSV-F immunogenicity studies in mice and running the corresponding immunological assays; Kate Broderick (Inovio, San Diego) for providing on-site training using the Elgen DNA Delivery System; Tina Scalzo and Melissa Sackal for conducting the ELISA and lung titer assays in the cotton rat study; Giuseppe Palladino and his serology team; and James Monroe and Kristian Friedrich for assisting in the respiratory syncytial virus neutralization assay. Funding for the HIV studies was provided by HIV Vaccine Research and Design Grant 5P01AI066287.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3437863/
22 August 2013
Enhanced Delivery and Potency of Self-Amplifying mRNA Vaccines by Electroporation in Situ
Yen Cu 1,†, Kate E. Broderick 2, Kaustuv Banerjee 1, Julie Hickman 1, Gillis Otten 1, Susan Barnett 1, Gleb Kichaev 2, Niranjan Y.
Sardesai 2, Jeffrey B. Ulmer 1 and Andrew Geall 1,* email
Abstract: 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
Publication date Aug 8, 2013
Pegylated liposomes for delivery of immunogen encoding rna
Inventors Andrew Geall, Ayush Verma
Patent-US 20130202684 A1
ABSTRACT
Nucleic acid immunisation is achieved by delivering RNA encapsulated within a PEGylated liposome. The RNA encodes an immunogen of interest. The PEG has an average molecular mass of between 1 kDa and 3 kDa. Thus the invention provides a liposome having a lipid bilayer encapsulating an aqueous core, wherein: (i) the lipid bilayer comprises at least one lipid which includes a polyethylene glycol moiety, such that polyethylene glycol is present on the liposome's exterior, wherein the average molecular mass of the polyethylene glycol is between 1 kDa and 3 kDa; and (ii) the aqueous core includes a RNA which encodes an immunogen. These liposomes are suitable for in vivo delivery of the RNA to a vertebrate cell and so they are useful as components in pharmaceutical compositions for immunising subjects against various diseases.
clip taken from long patent description-
A further study confirmed that the 0.1 µg of liposome-encapsulated RNA gave much higher anti-F IgG responses (15 days post-second dose) than 0.1 µg of delivered DNA, and even was more immunogenic than 20 µg plasmid DNA encoding the F antigen, delivered by electroporation (Elgen™ DNA Delivery System, Inovio).
Monday, September 9, 2013
-conference-
Vaccine Delivery and Stabilization:
Improving the Reach of Vaccines
-presentation-
14:00 – 14:30 Non-viral delivery of self-amplifying mRNA vaccines
Andrew Geall, Novartis, USA
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