Fig. 8.

mRNA modifications and delivery for viral vaccines. a General lipid nanoparticle formulations for mRNA delivery, peg-ylated lipids improve circulation while cholesterol and cationic lipids provide structural stability and facilitate endosomal escape and cellular uptake, respectively. b Cryo-EM image of a lipid nanoparticle. c Commonly utilized mRNA modifications that increase the efficacy of the delivered mRNA by increasing protein expression and mRNA stability while mitigating immune activation via pattern recognition receptors. d Mechanism of action for viral vaccines. Following delivery and cellular uptake of the mRNA encapsulated lipid nanoparticles , the transcript is able to escape the endosome and undergo translation, in this schematic the mRNA codes for the spike protein. T he spike protein is then processed by proteases and presented to T cells in lymph nodes via the MHC-II and TCR complex. Next, T cells begin to proliferate and differentiate into effector T cells and T follicle helper cells that can stimulate B cells to produce antibodies specific o the spike protein antigen. Following future exposure to SARS-CoV2, the patient’s immune system will be primed and capable of combating the virus. e Serum samples collected 23 days (“preboost”) and 46 days (“postboost”) from hACE2 transgenic mice treated following initial priming. Lipid nanoparticle  RBD-hFc mRNA treated mice display elevated SARS-CoV-2 spike-specific IgG antibodies (e1) and neutralizing antibodies (e2) following the booster compared to mRNA delivered without a lipid nanoparticle  and lipid nanoparticles without the target mRNA. f Survival of mice groups following treatment shows that boosted mice had a higher survival rate. g Weight of treated mice returned normal two weeks post booster for mice treated with lipid nanoparticle  RBD-hFc mRNA. Untreated mice did not survive past day 7. Reproduced with permission from ref [173, 174].