Investigating the Impact of Delivery System Design on the Efficacy of Self-Amplifying RNA Vaccines


Authors: G. Anderluzzi, G. Lou, S. Gallorini, M. Brazzoli, R. Johnson, D.T. O'Hagan, B.C. Baudner and Y. Perrie

Journal: Vaccines

DOI: 10.3390/vaccines8020212

Publication - Abstract

May 08, 2020

mRNA Polymeric Nanoparticles Nucleic Acid Lipid Nanoparticles

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.

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