Straight to the point: targeted mRNA-delivery to immune cells for improved vaccine design

Abstract

With the deepening of our understanding of adaptive immunity at the cellular and molecular level, targeting antigens directly to immune cells has proven to be a successful strategy to develop innovative and potent vaccines. Indeed, it offers the potential to increase vaccine potency and/or modulate immune response quality while reducing off-target effects. With mRNA-vaccines establishing themselves as a versatile technology for future applications, in the last years several approaches have been explored to target nanoparticles-enabled mRNA-delivery systems to immune cells, with a focus on dendritic cells. Dendritic cells (DCs) are the most potent antigen presenting cells and key mediators of B- and T-cell immunity, and therefore considered as an ideal target for cell-specific antigen delivery. Indeed, improved potency of DC-targeted vaccines has been proved in vitro and in vivo. This review discusses the potential specific targets for immune system-directed mRNA delivery, as well as the different targeting ligand classes and delivery systems used for this purpose.

Innate and Adaptive Immune Parameters following mRNA Vaccination in Mice

“…The effect of eLNP treatment on monocyte-derived dendritic cells resulted in a maturation of signaling via the upregulation of CD40 followed by cytokine secretion. Interestingly, the phosphorylation of TANK binding kinase 1 (pTBK1) and interferon response factor 7 (pIRF7) is the downstream signaling of monocyte-derived DC maturation [9,30]. In agreement with the above results, we also witnessed an increase in mature DCs and activated NK cells in the lymph nodes.…”

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