TALL · Targeted Antigen deLivery to Langerin: molecular basis of recognition and its implication in antigen uptake, processing and presentation to T cells
„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“
- Период
- 2020-09-01 → 2023-06-30
- Финансиране от ЕС
- 244 210 €
- Участници
- 2
- Схема
- MSCA-IF
Линиите свързват координатора с партньорите.
Накратко на български
Микроиглени за доставка на ваксини директно в кожата изследват как специфични молекули активират дендритните клетки и Т-лимфоцитите. Този метод може да направи ваксинацията по-безболезнена и да подобри имунния отговор при лечение на рак.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Резултати накратко
Targeted Antigen deLivery to Langerin: molecular basis of recognition and its implication in antigen uptake, processing and presentation to T cells
The aim of the project was to improve vaccine delivery methods beyond traditional hypodermal needles due to their drawbacks such as pain, invasiveness, and disposal costs. The proposed solution involves using microneedle patches to deliver vaccines directly into the skin's epidermis, targeting immune cells like dendritic cells for a more effective response. The approach could revolutionize vaccination by making it less painful, easier to self-administer, and cost-effective for disposal. It also holds promise for cancer immunotherapy, enhancing immune responses against cancer cells. To accomplish this project the main objectives were, first, engineering an antigenic scaffold that combines a langerin-targeted glycomimetic ligand with a T cell-stimulating peptide. This scaffold is meant to trigger immune responses for vaccine development. Second, studying the process of antigen uptake, processing, and presentation to T cells. This includes testing specificity with other skin cell receptors, monitoring antigen uptake by Langerin-expressing cell lines, and evaluating T cell activation and proliferation. Third, developing a system for transcutaneous cancer vaccination, leveraging the advantages of this novel approach over traditional methods. This could provide insights into immune cell activation and the induction of T cell responses.
Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз
Цел на проекта
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.
Оригинален текст от CORDIS (на английски).
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Данни: CORDIS, © Европейски съюз