Dr. Ramin Oskoui shared a critical new CELL (Verbeke) paper that describes the Innate immune mechanisms of mRNA vaccines, how the innate immune and adaptive immunity work (interact & primed) in

by Paul Alexander

response to COVID gene injections; key of Verbeke is to inform enabling tailoring mRNA & carrier molecules to develop mRNA vaccines with greater effectiveness & milder adverse events in the future.

The nucleoside-modified mRNA vaccines against coronavirus disease 2019 (COVID-19), i.e., BNT162b2 (Comirnaty) from Pfizer/BioNTech and mRNA-1273 (Spikevax) from Moderna, are the first mRNA products to receive approval from the Food and Drug Administration (FDA) or the European Medicines Agency (EMA). The two key components of these vaccines are (1) nucleoside-modified mRNA (Kariko´ et al., 2005), which encodes the antigenic protein of interest (in this case, the spike protein of severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]), and (2) lipid nanoparticles containing ionizable lipids (iLNPs), which enable efficient delivery of intact mRNA to the cytoplasm of cells that can then translate the encoded protein (Cullis and Hope, 2017).



‘However, little is known about which aspects of innate immunity are critical to drive protective immune responses and which are dispensable. Also lacking is a detailed mechanistic understanding of how innate immune pathways modulate adaptive immunity in mRNA vaccine responses. In this review, we focus on the innate immune stimulation by mRNA-iLNP vaccines, discuss recent insights gained from descriptive and hypothesis-driven studies on the dynamics and activation of innate immune cells, and explore the possible molecular mechanisms that contribute to the immunogenicity and reactogenicity of this novel vaccine platform.’