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. 2022 Jun 28;7:71. doi: 10.1038/s41541-022-00485-x

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© The Author(s) 2022

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 3 — a Innate Immune response to mRNA vaccines The delivery of the mRNA molecules into the cytosol is followed by the detection of the mRNA molecules by TLRs. Double-stranded RNA molecules co-delivered as impurities or produced from SAM or as secondary structures are additionally detected by RLRs (RIG-1, MDA-5). These drive cytokine and chemokine responses that recruit more innate cells to the injection site. Amplified interferon response can result in the activation of OAS/PKR whose signals impede translation, protein expression and antigen presentation. b Adaptive Immune response to mRNA vaccines. Following In vivo delivery of the mRNA vaccine, the mRNA molecules with the delivery vehicles are (1) uptaken by cells such as DCs at the site of injection by endocytosis with subsequent delivery into the endosomes. This is followed by (2) endosomal escape of the mRNA molecules into the cytosol and subsequent (3) translation in the cytosol to produce the encoded protein. The produced protein may be retained in the cytosol where it is subsequently channelled for (4,5,6) proteasomal-MHCI pathway which would eventually drive a CD8 T cell response. Some of the proteins may also become (7) membrane-bound and expressed on the surface or (8) secreted/shed. Some of the secreted or expressed proteins may be (9) recycled by endocytosis and subsequently channelled through the MHCII-restricted presentation to eventually drive CD4 T cell response. B-cell and T-cell responses occur by virtue of their interactions with the secreted or membrane-bound proteins and MHC-antigen complexes respectively. (10) These adaptive responses prevent infection and facilitate the elimination of the pathogen upon encounter through antibody production, cytokine release and cytotoxic activities.