1. Academic Validation
  2. Optimization of Lipid Nanoparticles for Intramuscular Administration of mRNA Vaccines

Optimization of Lipid Nanoparticles for Intramuscular Administration of mRNA Vaccines

  • Mol Ther Nucleic Acids. 2019 Apr 15;15:1-11. doi: 10.1016/j.omtn.2019.01.013.
Kimberly J Hassett 1 Kerry E Benenato 1 Eric Jacquinet 1 Aisha Lee 1 Angela Woods 1 Olga Yuzhakov 1 Sunny Himansu 1 Jessica Deterling 1 Benjamin M Geilich 1 Tatiana Ketova 1 Cosmin Mihai 1 Andy Lynn 1 Iain McFadyen 1 Melissa J Moore 1 Joseph J Senn 1 Matthew G Stanton 1 Örn Almarsson 1 Giuseppe Ciaramella 1 Luis A Brito 2
Affiliations

Affiliations

  • 1 Moderna Therapeutics, 200 Technology Square, Cambridge, MA 02139, USA.
  • 2 Moderna Therapeutics, 200 Technology Square, Cambridge, MA 02139, USA. Electronic address: luis.brito@modernatx.com.
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.

Keywords

LNP; formulation; immunogenicity; intramuscular; lipids; mRNA; tolerability; vaccines.

Figures
Products