The role of nanoparticle format and route of administration on self-amplifying mRNA vaccine potency.
Immunogenicity
Lipid nanoparticles
Polymeric nanoparticles
RNA vaccines
Route of administration
Self-amplifying RNA
Solid lipid nanoparticles
saRNA
Journal
Journal of controlled release : official journal of the Controlled Release Society
ISSN: 1873-4995
Titre abrégé: J Control Release
Pays: Netherlands
ID NLM: 8607908
Informations de publication
Date de publication:
02 2022
02 2022
Historique:
received:
20
06
2021
revised:
26
11
2021
accepted:
06
12
2021
pubmed:
14
12
2021
medline:
17
2
2022
entrez:
13
12
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 34896446
pii: S0168-3659(21)00659-3
doi: 10.1016/j.jconrel.2021.12.008
pmc: PMC8660137
pii:
doi:
Substances chimiques
COVID-19 Vaccines
0
Lipid Nanoparticles
0
Liposomes
0
RNA, Messenger
0
Vaccines, Synthetic
0
mRNA Vaccines
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
388-399Informations de copyright
Copyright © 2021. Published by Elsevier B.V.
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