Examining the role of mRNA-LNP components in modulating inflammatory responses to mRNA vaccines

Current licensed mRNA vaccines have been reported to cause inflammatory side effects in some vaccinated individuals. The main objective of this work was to investigate correlations between mRNA and lipid nanoparticles (LNP) components and systemic inflammatory responses. Our findings revealed strong associations between ionizable lipid structure, mRNA chemical modifications, and the magnitude and profile of systemic inflammation following exposure to mRNA–LNP formulations. Collectively, these results highlight the importance of understanding the molecular features of mRNA–LNP components to guide the rational design of safer and more effective mRNA vaccines.