Specific protein antigen delivery to human Langerhans cells in intact skin
| Autor: | Barbara Del Frari, Stephan Sigl, Jessica Schulze, Mareike Rentzsch, Felix F. Fuchsberger, Juliane Rademacher, Helen Strandt, Lydia Bellmann, Christoph Rademacher, Jil Busmann, Claudia Zelle-Rieser, Robert Wawrzinek, Patrizia Stoitzner |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Langerin
Injections Intradermal THP-1 Cells Immunology Green Fluorescent Proteins Human skin Protein degradation Ligands Immune system Antigen Antigens CD vaccine Chlorocebus aethiops microinjection Immunology and Allergy Animals Humans C-type lectins Lectins C-Type Langerhans cells Antigens Antigen-presenting cell Original Research Miniaturization biology Epidermis (botany) Chemistry targeted delivery RC581-607 Cell biology Protein Transport HEK293 Cells Mannose-Binding Lectins Nanomedicine Needles transdermal COS Cells Proteolysis Vaccines Subunit biology.protein microinjection Langerhans cells subunit vaccine Immunologic diseases. Allergy Antibody Protein Binding |
| Zdroj: | Frontiers in immunology Frontiers in Immunology Europe PubMed Central Frontiers in Immunology, Vol 12 (2021) |
| Popis: | Immune modulating therapies and vaccines are in high demand, not least to the recent global spread of SARS-CoV2. To achieve efficient activation of the immune system, professional antigen presenting cells have proven to be key coordinators of such responses. Especially targeted approaches, actively directing antigens to specialized dendritic cells, promise to be more effective and accompanied by reduced payload due to less off-target effects. Although antibody and glycan-based targeting of receptors on dendritic cells have been employed, these are often expensive and time-consuming to manufacture or lack sufficient specificity. Thus, we applied a small-molecule ligand that specifically binds Langerin, a hallmark receptor on Langerhans cells, conjugated to a model protein antigen.Viamicroneedle injection, this construct was intradermally administered into intact human skin explants, selectively loading Langerhans cells in the epidermis. The ligand-mediated cellular uptake outpaces protein degradation resulting in intact antigen delivery. Due to the pivotal role of Langerhans cells in induction of immune responses, this approach of antigen-targeting of tissue-resident immune cells offers a novel way to deliver highly effective vaccines with minimally invasive administration. |
| Databáze: | OpenAIRE |
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