Distinct dynamics of mRNA LNPs in mice and nonhuman primates revealed by in vivo imaging.

The characterization of vaccine distribution to relevant tissues after in vivo administration is critical to understanding their mechanisms of action. Vaccines based on mRNA lipid nanoparticles (LNPs) are now being widely considered against infectious diseases and cancer. Here, we used in vivo imaging approaches to compare the trafficking of two LNP formulations encapsulating mRNA following intramuscular administration: DLin-MC3-DMA (MC3) and the recently developed DOG-IM4.

Nonclinical safety assessment of an mRNA Covid-19 vaccine candidate following repeated administrations and biodistribution.

Messenger RNA (mRNA) vaccines have demonstrated efficacy against Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) in humans. mRNA technology holds tremendous potential for rapid control and prevention of emergencies due to its flexibility with respect to production, application, and design for an efficacious and safe use in humans. We assessed the toxicity and biodistribution of MRT5500, an mRNA vaccine encoding for the full-length of the SARS-CoV-2 spike protein and delivered by lipid nanoparticles (LNPs) containing a novel ionizable lipid, Lipid-1 in preclinical animal models.

The impact of nucleoside base modification in mRNA vaccine is influenced by the chemistry of its lipid nanoparticle delivery system.

The use of modified nucleosides is an important approach to mitigate the intrinsic immunostimulatory activity of exogenous mRNA and to increase its translation for mRNA therapeutic applications. However, for vaccine applications, the intrinsic immunostimulatory nature of unmodified mRNA could help induce productive immunity. Additionally, the ionizable lipid nanoparticles (LNPs) used to deliver mRNA vaccines can possess immunostimulatory properties that may influence the impact of nucleoside modification.

An imidazole modified lipid confers enhanced mRNA-LNP stability and strong immunization properties in mice and non-human primates.

The mRNA vaccine technology has promising applications to fight infectious diseases as demonstrated by the licensing of two mRNA-based vaccines, Comirnaty® (Pfizer/BioNtech) and Spikevax® (Moderna), in the context of the Covid-19 crisis. Safe and effective delivery systems are essential to the performance of these vaccines and lipid nanoparticles (LNPs) able to entrap, protect and deliver the mRNA in vivo are considered by many as the current "best in class". Nevertheless, current mRNA/LNP vaccine technology has still some limitations, one of them being thermostability, as evidenced by the ultracold distribution chain required for the licensed vaccines.