Specific Protein Antigen Delivery to Human Langerhans Cells in Intact Skin
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...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-10-01
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| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.732298/full |
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| author | Mareike Rentzsch Mareike Rentzsch Robert Wawrzinek Robert Wawrzinek Claudia Zelle-Rieser Helen Strandt Lydia Bellmann Felix F. Fuchsberger Jessica Schulze Jil Busmann Juliane Rademacher Stephan Sigl Barbara Del Frari Patrizia Stoitzner Christoph Rademacher |
| author_facet | Mareike Rentzsch Mareike Rentzsch Robert Wawrzinek Robert Wawrzinek Claudia Zelle-Rieser Helen Strandt Lydia Bellmann Felix F. Fuchsberger Jessica Schulze Jil Busmann Juliane Rademacher Stephan Sigl Barbara Del Frari Patrizia Stoitzner Christoph Rademacher |
| author_sort | Mareike Rentzsch |
| collection | DOAJ |
| description | 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. Via microneedle 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. |
| first_indexed | 2024-12-22T11:41:40Z |
| format | Article |
| id | doaj.art-e31a5a90189840738b7687431502dac3 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-22T11:41:40Z |
| publishDate | 2021-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-e31a5a90189840738b7687431502dac32022-12-21T18:27:17ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-10-011210.3389/fimmu.2021.732298732298Specific Protein Antigen Delivery to Human Langerhans Cells in Intact SkinMareike Rentzsch0Mareike Rentzsch1Robert Wawrzinek2Robert Wawrzinek3Claudia Zelle-Rieser4Helen Strandt5Lydia Bellmann6Felix F. Fuchsberger7Jessica Schulze8Jil Busmann9Juliane Rademacher10Stephan Sigl11Barbara Del Frari12Patrizia Stoitzner13Christoph Rademacher14Department of Biomolecular Systems, Max-Planck-Institute of Colloids and Interfaces, Potsdam, GermanyDepartment of Pharmaceutical Sciences, University of Vienna, Vienna, AustriaDepartment of Biomolecular Systems, Max-Planck-Institute of Colloids and Interfaces, Potsdam, GermanyDepartment of Pharmaceutical Sciences, University of Vienna, Vienna, AustriaLangerhans Cell Research Lab, Department of Dermatology, Venereology and Allergology, Medical University of Innsbruck, Innsbruck, AustriaLangerhans Cell Research Lab, Department of Dermatology, Venereology and Allergology, Medical University of Innsbruck, Innsbruck, AustriaLangerhans Cell Research Lab, Department of Dermatology, Venereology and Allergology, Medical University of Innsbruck, Innsbruck, AustriaDepartment of Biomolecular Systems, Max-Planck-Institute of Colloids and Interfaces, Potsdam, GermanyDepartment of Biomolecular Systems, Max-Planck-Institute of Colloids and Interfaces, Potsdam, GermanyDepartment of Biomolecular Systems, Max-Planck-Institute of Colloids and Interfaces, Potsdam, GermanyDepartment of Biomolecular Systems, Max-Planck-Institute of Colloids and Interfaces, Potsdam, GermanyDepartment of Plastic, Reconstructive and Aesthetic Surgery, Medical University of Innsbruck, Innsbruck, AustriaDepartment of Plastic, Reconstructive and Aesthetic Surgery, Medical University of Innsbruck, Innsbruck, AustriaLangerhans Cell Research Lab, Department of Dermatology, Venereology and Allergology, Medical University of Innsbruck, Innsbruck, AustriaDepartment of Biomolecular Systems, Max-Planck-Institute of Colloids and Interfaces, Potsdam, GermanyImmune 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. Via microneedle 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.https://www.frontiersin.org/articles/10.3389/fimmu.2021.732298/fulltargeted deliveryC-type lectinsvaccinesubunit vaccinetransdermalmicroinjection |
| spellingShingle | Mareike Rentzsch Mareike Rentzsch Robert Wawrzinek Robert Wawrzinek Claudia Zelle-Rieser Helen Strandt Lydia Bellmann Felix F. Fuchsberger Jessica Schulze Jil Busmann Juliane Rademacher Stephan Sigl Barbara Del Frari Patrizia Stoitzner Christoph Rademacher Specific Protein Antigen Delivery to Human Langerhans Cells in Intact Skin Frontiers in Immunology targeted delivery C-type lectins vaccine subunit vaccine transdermal microinjection |
| title | Specific Protein Antigen Delivery to Human Langerhans Cells in Intact Skin |
| title_full | Specific Protein Antigen Delivery to Human Langerhans Cells in Intact Skin |
| title_fullStr | Specific Protein Antigen Delivery to Human Langerhans Cells in Intact Skin |
| title_full_unstemmed | Specific Protein Antigen Delivery to Human Langerhans Cells in Intact Skin |
| title_short | Specific Protein Antigen Delivery to Human Langerhans Cells in Intact Skin |
| title_sort | specific protein antigen delivery to human langerhans cells in intact skin |
| topic | targeted delivery C-type lectins vaccine subunit vaccine transdermal microinjection |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.732298/full |
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