Distinct innate immune activation profiles of an mRNA-lipid nanoparticle vaccine compared to the empty lipid...

While messenger RNA- RNA-lipid nanoparticle (mRNA-LNP) vaccines are known to be immunogenic, the specific innate immune cells activated and the distinct contributions of the LNP and mRNA to the immune response remain unclear.

Using spectral flow cytometry and a multiplex cytokine assay, we define the change in expression of co-stimulatory molecules in specific innate immune cell populations and cytokine production from healthy human peripheral blood mononuclear cells (PBMCs) in response to LNP and mRNA-LNP.

Our data reveal distinct activation profiles induced by the BNT162b2 vaccine formulation LNP and mRNA-LNP. The LNP component primarily activated monocytes, upregulating antigen presentation and costimulatory molecules, and also induced costimulatory molecule expression on type 1 conventional dendritic cells (cDC1) and plasmacytoid DCs (pDCs) independently of the presence of mRNA. The mRNA-LNP activated B cells in contrast to empty LNP and induced cDC2 responses. The presence of mRNA enhanced GM-CSF and IL-10 production in culture but did not induce classic proinflammatory cytokines like TNF-α, IL-1β, or IL-6.

This study defines the innate immune responses induced by the BNT162b2 vaccine formulation LNP and mRNA-LNP. Upregulation of proteins that support antigen presentation and communication with lymphocytes on monocytes and B cells were reflective of LNP and mRNA-LNP stimulation. Cytokine production was relatively modest with GM-CSF and IL-10 predominating. These findings provide insights into the mechanisms underlying immune responses to mRNA-LNP vaccine components.