Mechanism of action and immune response induced by mRNA vaccines. 1) mRNA vaccines enter the cells through different mechanisms depending on the nature and size of the nanoparticles, such as clathrin-, caveolin- and receptor-mediated endocytosis, micropinocytosis, phagocytosis or diffusion across the cell membrane (47). 2) After reaching the cytoplasm, mRNAs are translated by the ribosomes into the encoded protein. 3) The protein is processed by the proteasome into small antigenic peptides. 4) The peptides are presented at the surface of the antigen presenting cell by major histocompatibility complex (MHC) molecules to prime CD4+ and CD8+ T cells through, respectively, MHC-II or MHC-I interaction with the T cell receptor (TCR), to activate humoral and cellular adaptive responses. 5) Exogenous mRNAs can be detected by the innate immune system through binding to pattern recognition receptors (PRRs) localised at the endosomal membrane or in the cytosol, inducing the transcription and translation (6) of proinflammatory factors, such as type 1 interferons (IFN-I), IFN-stimulated genes (ISGs) and RNases. NF-κB, nuclear factor κB. Created with BioRender.com.