A trypanosome-derived immunotherapeutics platform elicits potent high-affinity antibodies, negating the effects of the synthetic opioid fentanyl
Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved..
Poorly immunogenic small molecules pose challenges for the production of clinically efficacious vaccines and antibodies. To address this, we generate an immunization platform derived from the immunogenic surface coat of the African trypanosome. Through sortase-based conjugation of the target molecules to the variant surface glycoprotein (VSG) of the trypanosome surface coat, we develop VSG-immunogen array by sortase tagging (VAST). VAST elicits antigen-specific memory B cells and antibodies in a murine model after deploying the poorly immunogenic molecule fentanyl as a proof of concept. We also develop a single-cell RNA sequencing (RNA-seq)-based computational method that synergizes with VAST to specifically identify memory B cell-encoded antibodies. All computationally selected antibodies bind to fentanyl with picomolar affinity. Moreover, these antibodies protect mice from fentanyl effects after passive immunization, demonstrating the ability of these two coupled technologies to elicit therapeutic antibodies to challenging immunogens.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:42 |
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| Enthalten in: |
Cell reports - 42(2023), 2 vom: 28. Feb., Seite 112049 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Triller, Gianna [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 04.10.2023 Date Revised 24.10.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.celrep.2023.112049 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 100 | 1 | |a Triller, Gianna |e verfasserin |4 aut | |
| 245 | 1 | 2 | |a A trypanosome-derived immunotherapeutics platform elicits potent high-affinity antibodies, negating the effects of the synthetic opioid fentanyl |
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| 500 | |a Date Completed 04.10.2023 | ||
| 500 | |a Date Revised 24.10.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a Poorly immunogenic small molecules pose challenges for the production of clinically efficacious vaccines and antibodies. To address this, we generate an immunization platform derived from the immunogenic surface coat of the African trypanosome. Through sortase-based conjugation of the target molecules to the variant surface glycoprotein (VSG) of the trypanosome surface coat, we develop VSG-immunogen array by sortase tagging (VAST). VAST elicits antigen-specific memory B cells and antibodies in a murine model after deploying the poorly immunogenic molecule fentanyl as a proof of concept. We also develop a single-cell RNA sequencing (RNA-seq)-based computational method that synergizes with VAST to specifically identify memory B cell-encoded antibodies. All computationally selected antibodies bind to fentanyl with picomolar affinity. Moreover, these antibodies protect mice from fentanyl effects after passive immunization, demonstrating the ability of these two coupled technologies to elicit therapeutic antibodies to challenging immunogens | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a CP: Immunology | |
| 650 | 4 | |a Trypanosoma brucei | |
| 650 | 4 | |a antibody repertoire analysis | |
| 650 | 4 | |a fentanyl | |
| 650 | 4 | |a humoral immunity | |
| 650 | 4 | |a immunological memory | |
| 650 | 4 | |a opioid overdose | |
| 650 | 4 | |a sortase | |
| 650 | 4 | |a variant surface glycoprotein | |
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| 650 | 7 | |a Fentanyl |2 NLM | |
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| 650 | 7 | |a Variant Surface Glycoproteins, Trypanosoma |2 NLM | |
| 700 | 1 | |a Vlachou, Evi P |e verfasserin |4 aut | |
| 700 | 1 | |a Hashemi, Hamidreza |e verfasserin |4 aut | |
| 700 | 1 | |a van Straaten, Monique |e verfasserin |4 aut | |
| 700 | 1 | |a Zeelen, Johan P |e verfasserin |4 aut | |
| 700 | 1 | |a Kelemen, Yosip |e verfasserin |4 aut | |
| 700 | 1 | |a Baehr, Carly |e verfasserin |4 aut | |
| 700 | 1 | |a Marker, Cheryl L |e verfasserin |4 aut | |
| 700 | 1 | |a Ruf, Sandra |e verfasserin |4 aut | |
| 700 | 1 | |a Svirina, Anna |e verfasserin |4 aut | |
| 700 | 1 | |a Chandra, Monica |e verfasserin |4 aut | |
| 700 | 1 | |a Urban, Katharina |e verfasserin |4 aut | |
| 700 | 1 | |a Gkeka, Anastasia |e verfasserin |4 aut | |
| 700 | 1 | |a Kruse, Sebastian |e verfasserin |4 aut | |
| 700 | 1 | |a Baumann, Andreas |e verfasserin |4 aut | |
| 700 | 1 | |a Miller, Aubry K |e verfasserin |4 aut | |
| 700 | 1 | |a Bartel, Marc |e verfasserin |4 aut | |
| 700 | 1 | |a Pravetoni, Marco |e verfasserin |4 aut | |
| 700 | 1 | |a Stebbins, C Erec |e verfasserin |4 aut | |
| 700 | 1 | |a Papavasiliou, F Nina |e verfasserin |4 aut | |
| 700 | 1 | |a Verdi, Joseph P |e verfasserin |4 aut | |
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