Optimization of Lipid Nanoparticles for Intramuscular Administration of MRNA Vaccines

Overview

Journal Mol Ther Nucleic Acids

Publisher Cell Press

Date 2019 Feb 21

PMID 30785039

Citations 325

Authors

Kimberly J Hassett

Kerry E Benenato

Eric Jacquinet

Aisha Lee

Angela Woods

Olga Yuzhakov

Sunny Himansu

Jessica Deterling

Benjamin M Geilich

Tatiana Ketova

Cosmin Mihai

Andy Lynn

Iain McFadyen

Melissa J Moore

Joseph J Senn

Matthew G Stanton

Orn Almarsson

Giuseppe Ciaramella

Luis A Brito

Affiliations

Soon will be listed here.

Abstract

mRNA vaccines have the potential to tackle many unmet medical needs that are unable to be addressed with conventional vaccine technologies. A potent and well-tolerated delivery technology is integral to fully realizing the potential of mRNA vaccines. Pre-clinical and clinical studies have demonstrated that mRNA delivered intramuscularly (IM) with first-generation lipid nanoparticles (LNPs) generates robust immune responses. Despite progress made over the past several years, there remains significant opportunity for improvement, as the most advanced LNPs were designed for intravenous (IV) delivery of siRNA to the liver. Here, we screened a panel of proprietary biodegradable ionizable lipids for both expression and immunogenicity in a rodent model when administered IM. A subset of compounds was selected and further evaluated for tolerability, immunogenicity, and expression in rodents and non-human primates (NHPs). A lead formulation was identified that yielded a robust immune response with improved tolerability. More importantly for vaccines, increased innate immune stimulation driven by LNPs does not equate to increased immunogenicity, illustrating that mRNA vaccine tolerability can be improved without affecting potency.

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