Fig. 1

Graphical abstract depicting the mechanisms of mRNA vaccines with various signal sequences in combating viral diseases. (A) The mRNA sequences are designed to encode an antigen, incorporating signal sequences derived from the virus’ origin, interleukin-6 (IL-6), and tissue plasminogen activator (tPA). (B) Lipid nanoparticles (LNPs) are prepared utilizing a microfluidic device. (C) The process involves multiple steps: (1) Dendritic cells (DCs) endocytose the mRNA vaccines encoding the antigen. Subsequently, the mRNAs escape from lysosomes and was translated by ribosomes. The signal recognition particle (SRP) then bound to the translated signal sequences via the SRP54M subunit, simultaneously attaching to the ribosome, thus forming an SRP-ribosome complex. This complex temporarily halte translation. (2) The SRP recognize the SRP receptor (SRP-R) on the endoplasmic reticulum (ER) membrane, facilitating the ribosome’s anchoring to the translocon, which allow the translation to resume. The nascent peptide chain traversed the membrane, entering the ER lumen, where the signal sequences were cleaved by signal peptidase. The elongating peptide chain undergo further processing and modification within the ER and Golgi complex. (3) The secreted antigens are potentially reabsorbed by DCs, subsequently being degraded into smaller fragments within endosomes. These fragments are then presented on the cell surface to helper T (Th) cells through major histocompatibility complex (MHC) class II T cell receptors (TCRs). (4) B cells, upon receiving the initial signal from the antigen through B cell receptors (BCRs) and a secondary signal from activated Th cells, become activated and differentiated into plasma cells. These plasma cells produce antibodies to neutralize the virus. (5) Intracellular antigens are degraded into smaller fragments by proteasomes. These fragments were then presented to cytotoxic T (Tc) cells via MHC class I TCRs. (6) The activated Tc cells secrete perforin and granzyme, which targeted and eradicated infected cells by inducing apoptosis