The role of nanoparticle format and route of administration on self-amplifying mRNA vaccine potency

Giulia Anderluzzi, Gustavo Lou, Stuart Woods, Signe Tandrup Schmidt, Simona Gallorini, Michela Brazzoli, Russell Johnson, Craig W. Roberts, Derek T. O'Hagan, Barbara C. Baudner, Yvonne Perrie

Research output: Contribution to journalArticlepeer-review

36 Citations (Scopus)
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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.
Original languageEnglish
Pages (from-to)388-399
Number of pages12
JournalJournal of Controlled Release
Early online date10 Dec 2021
Publication statusPublished - 28 Feb 2022


  • solid lipid nanoparticles
  • immunogenicity
  • self-amplifying RNA
  • saRNA
  • polymeric nanoparticles
  • route of administration
  • RNA vaccines
  • lipid nanoparticles


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