The role of nanoparticle format and route of administration on self-amplifying mRNA vaccine potency
Articolo
Data di Pubblicazione:
2022
Citazione:
The role of nanoparticle format and route of administration on self-amplifying mRNA vaccine potency / G. Anderluzzi, G. Lou, S. Woods, S.T. Schmidt, S. Gallorini, M. Brazzoli, R. Johnson, C.W. Roberts, D.T. O'Hagan, B.C. Baudner, Y. Perrie. - In: JOURNAL OF CONTROLLED RELEASE. - ISSN 0168-3659. - 342:(2022 Feb), pp. 388-399. [10.1016/j.jconrel.2021.12.008]
Abstract:
The efficacy of RNA-based vaccines has been recently demonstrated, leading to the use of mRNA-based COVID19 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 RNAvaccine 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.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
Immunogenicity; Lipid nanoparticles; Polymeric nanoparticles; RNA vaccines; Route of administration; Self-amplifying RNA; Solid lipid nanoparticles; saRNA
Elenco autori:
G. Anderluzzi, G. Lou, S. Woods, S.T. Schmidt, S. Gallorini, M. Brazzoli, R. Johnson, C.W. Roberts, D.T. O'Hagan, B.C. Baudner, Y. Perrie
Link alla scheda completa: