Investigating the impact of delivery system design on the efficacy of self-amplifying RNA vaccines

Giulia Anderluzzi, Gustavo Lou, Simona Gallorini, Michela Brazzoli, Russell Johnson, Derek T. O'Hagan, Barbara C. Baudner, Yvonne Perrie

Research output: Contribution to journalArticle

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Abstract

Messenger RNA (mRNA)-based vaccines combine the positive attributes of both live-attenuated and subunit vaccines. In order for these to be applied for clinical use, they require to be formulated with delivery systems. However, there are limited in vivo studies which compare different delivery platforms. Therefore, we have compared four different cationic platforms: (1) liposomes, (2) solid lipid nanoparticles (SLNs), (3) polymeric nanoparticles (NPs) and (4) emulsions, to deliver a self-amplifying mRNA (SAM) vaccine. All formulations contained either the non-ionizable cationic lipid 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) or dimethyldioctadecylammonium bromide (DDA) and they were characterized in terms of physico-chemical attributes, in vitro transfection efficiency and in vivo vaccine potency. Our results showed that SAM encapsulating DOTAP polymeric nanoparticles, DOTAP liposomes and DDA liposomes induced the highest antigen expression in vitro and, from these, DOTAP polymeric nanoparticles were the most potent in triggering humoral and cellular immunity among candidates in vivo.
Original languageEnglish
Article number212
Number of pages22
JournalVaccines
Volume8
Issue number2
DOIs
Publication statusPublished - 8 May 2020

Keywords

  • vaccines
  • liposomes
  • LNPs
  • self-amplifying RNA

Projects

Research Output

Using microfluidics for scalable manufacturing of nanomedicines from bench to GMP: a case study using protein-loaded liposomes

Webb, C., Forbes, N., Roces, C. B., Anderluzzi, G., Lou, G., Abraham, S., Ingalls, L., Marshall, K., Leaver, T. J., Watts, J. A., Aylott, J. W. & Perrie, Y., 30 May 2020, In : International Journal of Pharmaceutics. 582, 12 p., 119266.

Research output: Contribution to journalArticle

2 Citations (Scopus)

Microfluidic manufacture of solid lipid nanoparticles: a case study on tristearin-based systems

Anderluzzi, G. & Perrie, Y., 31 Dec 2019, In : Drug Delivery Letters. 25 p.

Research output: Contribution to journalArticle

  • Student Theses

    Investigating alternative delivery systems for self-Amplifying RNA vaccines

    Author: Anderluzzi, G., 5 Mar 2020

    Supervisor: Perrie, Y. (Supervisor) & Roberts, C. (Supervisor)

    Student thesis: Doctoral Thesis

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