Targeted Delivery to Langerhans Cells

The skin represents an attractive organ for the application of novel vaccines since it harbours a large reservoir of resident immune cells capable of eliciting a systemic response against antigens. In particular, Langerhans cells (LCs) are located in the epidermis, the upper layer of the skin. Insight generated over the past decades has highlighted the ability of LCs to promote a systemic cytotoxic T cell response. These responses were primarily investigated using antibody-based delivery of antigens to LCs and were especially effective when Langerin was used as a targeted receptor. Langerin is a LC-restricted C-type lectin receptor. We have developed a small molecule ligand specific for Langerin that we here explore as the basis for antigen delivery via liposomal formulations (Wamhoff et al. (2019)). These nanoparticulate formulations can encapsulate small molecules and protein antigens and release their cargo intracellularly (Schulze et al. (2019)). We were able to show specific uptake of these liposomes into Langerin-expressing model cells as well as primary human LCs. Furthermore, we study their endosomal fate and intracellular processing. Overall, these highly specific nanoparticles potentially build the basis for innovative delivery of vaccines via the skin.