DOG-IM4 LNPs encapsulating influenza HA mRNA conferred strong immunization properties in mice and macaques and remarkable stability when stored liquid at 4 °C.
Does DOG-IM4 lipid nanoparticle delivery improve thermostability and immunization properties of mRNA vaccines in mice and macaques?
A novel imidazole modified lipid, DOG-IM4, improves the thermostability and immunization efficacy of mRNA-LNP vaccines in preclinical models.
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. We found that the thermostability of mRNA/LNP, could be improved by a novel imidazole modified lipid, DOG-IM4, in combination with standard helper lipids. DOG-IM4 comprises an ionizable head group consisting of imidazole, a dioleoyl lipid tail and a short flexible polyoxyethylene spacer between the head and tail. Here we describe the synthesis of DOG-IM4 and show that DOG-IM4 LNPs confer strong immunization properties to influenza HA mRNA in mice and macaques and a remarkable stability to the encapsulated mRNA when stored liquid in phosphate buffered saline at 4 °C. We speculate the increased stability to result from some specific attributes of the lipid's imidazole head group.
Ripoll et al. (2022) studied Infectious diseases (Influenza). DOG-IM4 lipid nanoparticles was evaluated on Immunization properties and thermostability. DOG-IM4 LNPs encapsulating influenza HA mRNA conferred strong immunization properties in mice and macaques and remarkable stability when stored liquid at 4 °C.