MRNA Vaccines

Abstract

The concept of developing mRNA as vaccine platform evolved over the last decades. mRNA uses host cells for antigen production, can induce B and T cell responses and does not rely on unwanted antigens that may interfere with booster doses like vector vaccines. Unmodified mRNA (uRNA) may be highly reactogenic; modification results not only in improved tolerability but also increases purity and potency. While self-amplifying mRNA (saRNA) leads to higher antigen expression, such constructs are much larger, and this may reduce stability. mRNA vaccines need to be formulated in a way that allows cell entry, e.g., by using carefully designed lipid nanoparticles (LNP). As response to the COVID-19 pandemic, mRNA vaccines were developed in less than one year from receiving the genetic code to licensure. The 2 marketed and modRNA products widely used today (162b2, Pfizer/Biontech; mRNA-1273, Moderna) differ in vitro in their ability to induce a CD8 T cell response. The development of a third vaccine, based in uRNA, was recently stopped. Both licensed modRNA vaccines have an acceptable reactogenicity and safety profile, a protection rate of ≥94% in large double-blind-randomized studies in adults and children ≥12-years of age with a vaccine efficacy against symptomatic disease of >90% in the 6-month follow-up period.