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Polymeric and lipid nanoparticles for delivery of self-amplifying RNA vaccines

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Title: Polymeric and lipid nanoparticles for delivery of self-amplifying RNA vaccines
Authors: Blakney, AK
McKay, PF
Hu, K
Samnuan, K
Jain, N
Brown, A
Thomas, A
Rogers, P
Polra, K
Sallah, H
Yeow, J
Zhu, Y
Stevens, MM
Geall, A
Shattock, RJ
Item Type: Journal Article
Abstract: Self-amplifying RNA (saRNA) is a next-generation vaccine platform, but like all nucleic acids, requires a delivery vehicle to promote cellular uptake and protect the saRNA from degradation. To date, delivery platforms for saRNA have included lipid nanoparticles (LNP), polyplexes and cationic nanoemulsions; of these LNP are the most clinically advanced with the recent FDA approval of COVID-19 based-modified mRNA vaccines. While the effect of RNA on vaccine immunogenicity is well studied, the role of biomaterials in saRNA vaccine effectiveness is under investigated. Here, we tested saRNA formulated with either pABOL, a bioreducible polymer, or LNP, and characterized the protein expression and vaccine immunogenicity of both platforms. We observed that pABOL-formulated saRNA resulted in a higher magnitude of protein expression, but that the LNP formulations were overall more immunogenic. Furthermore, we observed that both the helper phospholipid and route of administration (intramuscular versus intranasal) of LNP impacted the vaccine immunogenicity of two model antigens (influenza hemagglutinin and SARS-CoV-2 spike protein). We observed that LNP administered intramuscularly, but not pABOL or LNP administered intranasally, resulted in increased acute interleukin-6 expression after vaccination. Overall, these results indicate that delivery systems and routes of administration may fulfill different delivery niches within the field of saRNA genetic medicines.
Issue Date: 10-Oct-2021
Date of Acceptance: 16-Aug-2021
URI: http://hdl.handle.net/10044/1/91260
DOI: 10.1016/j.jconrel.2021.08.029
ISSN: 0168-3659
Publisher: Elsevier BV
Start Page: 201
End Page: 210
Journal / Book Title: Journal of Controlled Release
Volume: 338
Copyright Statement: © 2021 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Sponsor/Funder: Engineering & Physical Science Research Council (EPSRC)
Engineering and Physical Sciences Research Council (EPSRC)
Funder's Grant Number: EP/R013764/1
EP/R013764/1
Keywords: Pharmacology & Pharmacy
0903 Biomedical Engineering
0904 Chemical Engineering
1115 Pharmacology and Pharmaceutical Sciences
Publication Status: Published
Open Access location: https://doi.org/10.1016/j.jconrel.2021.08.029
Online Publication Date: 2021-08-18
Appears in Collections:Department of Infectious Diseases



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