Fig. 8. Lipid nanoparticles (LNP) can activate the innate immune response sans mRNA (eLNP).

eLNP will upregulate co-stimulatory makers on the surface of monocytes, DCs, and PBMCs that are necessary for T cell activation and antigen-processing and presentation. eLNP will then induce a productive humoral and cellular response. In older adults, however, eLNP upregulates the same co-stimulatory but to a much lesser degree while also upregulating PD-L1, an inhibitory marker that was all but absent in younger adults. Addition of eLNP also induced TGF-B production in older adults. Taken together, our study shows a mechanism that accounts for the decreased protection due to vaccination in older adults.