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CORDIS

Targeted Antigen deLivery to Langerin: molecular basis of recognition and its implication in antigen uptake, processing and presentation to T cells

Project description

Harnessing the skin's immune system could mean the end of needles for vaccinations

The skin is not only a physical barrier that protects our body from pathogens; it also plays a role in immunity. Targeting the activation of skin-resident immune cells could be a convenient and efficient way to deliver vaccines and other treatments. While the concept of a skin immune system was introduced nearly 40 years ago, we only recently learned about the full potential of these immune cells located in both the epidermis and dermis. In particular, Langerhans cells (LCs) are antigen-presenting cells located in the epidermis. The EU-funded TALL project is targeting antigen delivery to receptors on LCs with the goal of triggering an immune response with a simple transdermal patch as an alternative to intramuscular vaccination. Successful lab tests will pave the way for clinical trials and signal the end of needles for all those childhood vaccines and boosters.

Objective

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.

Coordinator

UNIVERSITAT WIEN
Net EU contribution
€ 244 209,60
Address
UNIVERSITATSRING 1
1010 Wien
Austria

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Region
Ostösterreich Wien Wien
Activity type
Higher or Secondary Education Establishments
Links
Total cost
€ 244 209,77

Participants (1)