The role of nanoparticle format and route of administration on self-amplifying mRNA vaccine potency
Anderluzzi, Giulia and Lou, Gustavo and Woods, Stuart and Schmidt, Signe Tandrup and Gallorini, Simona and Brazzoli, Michela and Johnson, Russell and Roberts, Craig W. and O'Hagan, Derek T. and Baudner, Barbara C. and Perrie, Yvonne (2022) The role of nanoparticle format and route of administration on self-amplifying mRNA vaccine potency. Journal of Controlled Release, 342. pp. 388-399. ISSN 0168-3659 (https://doi.org/10.1016/j.jconrel.2021.12.008)
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Abstract
The efficacy of RNA-based vaccines has been recently demonstrated, leading to the use of mRNA-based COVID-19 vaccines. The application of self-amplifying mRNA within these formulations may offer further enhancement to these vaccines, as self-amplifying mRNA replicons enable longer expression kinetics and more potent immune responses compared to non-amplifying mRNAs. To investigate the impact of administration route on RNA-vaccine potency, we investigated the immunogenicity of a self-amplifying mRNA encoding the rabies virus glycoprotein encapsulated in different nanoparticle platforms (solid lipid nanoparticles (SLNs), polymeric nanoparticles (PNPs) and lipid nanoparticles (LNPs)). These were administered via three different routes: intramuscular, intradermal and intranasal. Our studies in a mouse model show that the immunogenicity of our 4 different saRNA vaccine formulations after intramuscular or intradermal administration was initially comparable; however, ionizable LNPs gave higher long-term IgG responses. The clearance of all 4 of the nanoparticle formulations from the intramuscular or intradermal administration site was similar. In contrast, immune responses generated after intranasal was low and coupled with rapid clearance for the administration site, irrespective of the formulation. These results demonstrate that both the administration route and delivery system format dictate self-amplifying RNA vaccine efficacy.
ORCID iDs
Anderluzzi, Giulia, Lou, Gustavo, Woods, Stuart ORCID: https://orcid.org/0000-0002-3798-2074, Schmidt, Signe Tandrup, Gallorini, Simona, Brazzoli, Michela, Johnson, Russell, Roberts, Craig W. ORCID: https://orcid.org/0000-0002-0653-835X, O'Hagan, Derek T., Baudner, Barbara C. and Perrie, Yvonne;-
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Item type: Article ID code: 79776 Dates: DateEvent28 February 2022Published10 December 2021Published Online6 December 2021Accepted20 June 2021SubmittedSubjects: Medicine > Pharmacy and materia medica Department: Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences Depositing user: Pure Administrator Date deposited: 02 Mar 2022 08:50 Last modified: 21 Nov 2024 05:05 URI: https://strathprints.strath.ac.uk/id/eprint/79776