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The role of nanoparticle format and route of administration on self-amplifying mRNA vaccine potency.
Anderluzzi, Giulia; Lou, Gustavo; Woods, Stuart; Schmidt, Signe Tandrup; Gallorini, Simona; Brazzoli, Michela; Johnson, Russell; Roberts, Craig W; O'Hagan, Derek T; Baudner, Barbara C; Perrie, Yvonne.
  • Anderluzzi G; Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral St., Glasgow G4 0RE, Scotland, UK; GSK, Siena, Italy.
  • Lou G; Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral St., Glasgow G4 0RE, Scotland, UK; GSK, Siena, Italy.
  • Woods S; Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral St., Glasgow G4 0RE, Scotland, UK.
  • Schmidt ST; Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral St., Glasgow G4 0RE, Scotland, UK; Department of Infectious Disease Immunology, Center for Vaccine Research, Statens Serum Institut, Artillerivej 5, 2300 Copenhagen S, Denmark.
  • Gallorini S; GSK, Siena, Italy.
  • Brazzoli M; GSK, Siena, Italy.
  • Johnson R; GSK, Rockville, MD 9911, USA.
  • Roberts CW; Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral St., Glasgow G4 0RE, Scotland, UK.
  • O'Hagan DT; GSK, Rockville, MD 9911, USA.
  • Baudner BC; GSK, Siena, Italy.
  • Perrie Y; Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral St., Glasgow G4 0RE, Scotland, UK. Electronic address: yvonne.perrie@strath.ac.uk.
J Control Release ; 342: 388-399, 2022 02.
Article in English | MEDLINE | ID: covidwho-1562303
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Nanoparticles / COVID-19 Limits: Animals / Humans Language: English Journal: J Control Release Journal subject: Pharmacology Year: 2022 Document Type: Article Affiliation country: J.jconrel.2021.12.008

Full text: Available Collection: International databases Database: MEDLINE Main subject: Nanoparticles / COVID-19 Limits: Animals / Humans Language: English Journal: J Control Release Journal subject: Pharmacology Year: 2022 Document Type: Article Affiliation country: J.jconrel.2021.12.008