The skin is an attractive target in human vaccination harboring a dense network of immune cells. For instance, Lagerhans cells (LCs) are specialized in the identification of antigens derived from pathogens, and their subsequent internalization and presentation to induce a T cell response. The aim of the present proposal is to establish a novel mechanism for antigen delivery, targeted specifically to a particular receptor of LCs, Langerin, capable of triggering a T cell response. To this end, the vaccine scaffold will be composed of a T cell stimulating peptide covalently linked to a glycomimetic probe aiming exclusively to Langerin.
This project gathers the use of several techniques derived from both chemistry and biology at the disposal of immunology. First, molecular docking of the binding groove in complex with the antigenic peptide will be crucial to rationally design the vaccine scaffold. Once chosen, the most suitable candidate will be synthetized and analyzed by a combination of different Nuclear Magnetic Resonance (NMR) techniques. Elucidation of the antigen-Langerin affinity using NMR experiments will be critical to choose the most specific antigen to be further employed in biological tests. Antigen uptake will be monitored by flow cytometry and confocal imaging. Whole skin cell suspensions will be then employed to test the specificity of the construct. Finally, antigenic peptides will be tested for T cell activation and proliferation.
The translational outcome of this research will be applied in the design of transdermal patches, which represent an attractive approach to intramuscular vaccination, allowing targeted and pain-free delivery with minimal invasiveness.
Call for proposal
See other projects for this call