Fig. 6

In an mRNA vaccine, the mRNA is taken up by cells through endocytosis and subsequently released from the endosome to be converted into proteins by ribosomes. These proteins can activate the immune system in two primary ways: i) the proteins are broken down by proteasomes into peptides that are then displayed as antigens on the cell surface by MHC class I molecules, which bind to the TCR and activate CD8 + T cells to destroy infected cells by releasing perforin and granzyme; ii) proteins secreted externally are taken up by APCs and broken down into peptides that are then displayed on the cell surface by MHC class II molecules for recognition by CD4 + T cells, which can activate both cellular immune responses by producing cytokines and humoral immune responses by co-activating B cells. Additionally, single-stranded RNA and double-stranded RNA in mRNA vaccines bind to TLR in the endosome to activate antiviral innate immune responses through the production of type-I interferon (IFN-I), which leads to the induction of numerous IFN-1-stimulated genes involved in antiviral innate immunity, a process known as the self-adjuvant effect of sequence-engineered mRNA. Reprinted from [205] with permission from Springer Nature