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. 2021 Mar 25;8:635245. doi: 10.3389/fmolb.2021.635245

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Copyright © 2021 Borah, Deb, Al-Shar’i, Dahabiyeh, Venugopala, Singh, Shinu, Hussain, Deka, Chandrasekaran and Jaradat.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Diagrammatic representation of mechanism of antigen expression by the conventional mRNA (Top) and self-amplifying mRNA (SAM) vaccines (Bottom). (1) In this illustration, both conventional mRNA and SAM are shown to be formulated in lipid-derived nanoparticles (LNPs) to provide better stability; (2) The LNP formulated mRNA enters the cell through membrane-derived endocytosis processes; (3) The mRNA content shows endosomal escape to reach the cytosol; (4) In case of conventional type, the escaped mRNAs are immediately translated by the ribosomes to generate the protein of interest (Top), while SAM constructs undergoes translation to produce the replicase complex to exhibit self-amplification of the encoded mRNA, followed by translation of the antigen of interest to express the desired protein (Bottom); (5) Then the expressed proteins undergoes subsequent post-translational modification to appear as trans-membrane, intracellular or secreted protein; and (6) The expressed proteins are then broken down to peptides by the proteasome, and the peptide formed are presented to the immune system by the major histocompatibility complex (MHC).