Fig 5.

Effects of nucleoside-modified MERS-CoV mRNA vaccines on reducing mRNA-associated innate immune activation using RBD-mRNA as an example. (A) Schematic figures showing the production of inflammatory cytokines by unmodified RBD-mRNA (synthesized using UTP and 3 other nucleosides, GTP, ATP, and CTP). Such cytokines were blocked when pseudoU was used for the synthesis of mRNA together with other nucleosides (GTP, ATP, and CTP). (B) Examples of the detection of inflammatory cytokines (IL-6, IFN-α, and TNF-α) in sera of RBD-mRNA-injected BALB/c mice at 0, 2, and 6 hours postinjection. Unmodified (uridine, UTP) and modified (pseudouridine, pseudoU) RBD-mRNAs were used for the injection, and empty LNPs were included as a control (Ctrl). Significant differences between modified and unmodified RBD-mRNA groups are indicated. (C) RBD-mRNAs with pseudoU packaged at the indicated percentages were used to inject into BALB/c mice as indicated above, and related inflammatory cytokines (IL-6, IFN-α, and TNF-α) were detected at 0, 2, and 6 hours postinjection. Control (Ctrl), empty LNPs. (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)