A synthetic delivery vector for mucosal vaccination
Copyright © 2023 Elsevier Ltd. All rights reserved..
The success of mRNA-based vaccines during the Covid-19 pandemic has highlighted the value of this new platform for vaccine development against infectious disease. However, the CD8+ T cell response remains modest with mRNA vaccines, and these do not induce mucosal immunity, which would be needed to prevent viral spread in the healthy population. To address this drawback, we developed a dendritic cell targeting mucosal vaccination vector, the homopentameric STxB. Here, we describe the highly efficient chemical synthesis of the protein, and its in vitro folding. This straightforward preparation led to a synthetic delivery tool whose biophysical and intracellular trafficking characteristics were largely indistinguishable from recombinant STxB. The chemical approach allowed for the generation of new variants with bioorthogonal handles. Selected variants were chemically coupled to several types of antigens derived from the mucosal viruses SARS-CoV-2 and type 16 human papillomavirus. Upon intranasal administration in mice, mucosal immunity, including resident memory CD8+ T cells and IgA antibodies was induced against these antigens. Our study thereby identifies a novel synthetic antigen delivery tool for mucosal vaccination with an unmatched potential to respond to an urgent medical need.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:302 |
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| Enthalten in: |
Biomaterials - 302(2023) vom: 15. Nov., Seite 122298 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Billet, Anne [VerfasserIn] |
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| Links: |
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| Themen: |
Antibodies, Viral |
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| Anmerkungen: |
Date Completed 06.11.2023 Date Revised 06.11.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.biomaterials.2023.122298 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM362109028 |
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| 245 | 1 | 2 | |a A synthetic delivery vector for mucosal vaccination |
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| 500 | |a Date Completed 06.11.2023 | ||
| 500 | |a Date Revised 06.11.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023 Elsevier Ltd. All rights reserved. | ||
| 520 | |a The success of mRNA-based vaccines during the Covid-19 pandemic has highlighted the value of this new platform for vaccine development against infectious disease. However, the CD8+ T cell response remains modest with mRNA vaccines, and these do not induce mucosal immunity, which would be needed to prevent viral spread in the healthy population. To address this drawback, we developed a dendritic cell targeting mucosal vaccination vector, the homopentameric STxB. Here, we describe the highly efficient chemical synthesis of the protein, and its in vitro folding. This straightforward preparation led to a synthetic delivery tool whose biophysical and intracellular trafficking characteristics were largely indistinguishable from recombinant STxB. The chemical approach allowed for the generation of new variants with bioorthogonal handles. Selected variants were chemically coupled to several types of antigens derived from the mucosal viruses SARS-CoV-2 and type 16 human papillomavirus. Upon intranasal administration in mice, mucosal immunity, including resident memory CD8+ T cells and IgA antibodies was induced against these antigens. Our study thereby identifies a novel synthetic antigen delivery tool for mucosal vaccination with an unmatched potential to respond to an urgent medical need | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Mucosal immunity | |
| 650 | 4 | |a Resident memory T cells | |
| 650 | 4 | |a Shiga toxin B-Subunit | |
| 650 | 4 | |a Solid phase peptide synthesis | |
| 650 | 4 | |a Vaccination | |
| 650 | 7 | |a Vaccines, Synthetic |2 NLM | |
| 650 | 7 | |a Antigens |2 NLM | |
| 650 | 7 | |a Antibodies, Viral |2 NLM | |
| 700 | 1 | |a Hadjerci, Justine |e verfasserin |4 aut | |
| 700 | 1 | |a Tran, Thi |e verfasserin |4 aut | |
| 700 | 1 | |a Kessler, Pascal |e verfasserin |4 aut | |
| 700 | 1 | |a Ulmer, Jonathan |e verfasserin |4 aut | |
| 700 | 1 | |a Mourier, Gilles |e verfasserin |4 aut | |
| 700 | 1 | |a Ghazarian, Marine |e verfasserin |4 aut | |
| 700 | 1 | |a Gonzalez, Anthony |e verfasserin |4 aut | |
| 700 | 1 | |a Thai, Robert |e verfasserin |4 aut | |
| 700 | 1 | |a Urquia, Pauline |e verfasserin |4 aut | |
| 700 | 1 | |a Van Baelen, Anne-Cécile |e verfasserin |4 aut | |
| 700 | 1 | |a Meola, Annalisa |e verfasserin |4 aut | |
| 700 | 1 | |a Fernandez, Ignacio |e verfasserin |4 aut | |
| 700 | 1 | |a Deville-Foillard, Stéphanie |e verfasserin |4 aut | |
| 700 | 1 | |a MacDonald, Ewan |e verfasserin |4 aut | |
| 700 | 1 | |a Paolini, Léa |e verfasserin |4 aut | |
| 700 | 1 | |a Schmidt, Frédéric |e verfasserin |4 aut | |
| 700 | 1 | |a Rey, Félix A |e verfasserin |4 aut | |
| 700 | 1 | |a Kay, Michael S |e verfasserin |4 aut | |
| 700 | 1 | |a Tartour, Eric |e verfasserin |4 aut | |
| 700 | 1 | |a Servent, Denis |e verfasserin |4 aut | |
| 700 | 1 | |a Johannes, Ludger |e verfasserin |4 aut | |
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