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A trypanosome-derived immunotherapeutics platform elicits potent high-affinity antibodies, negating the effects of the synthetic opioid fentanyl
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 molecul...
Autores principales: | , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10387133/ https://www.ncbi.nlm.nih.gov/pubmed/36719797 http://dx.doi.org/10.1016/j.celrep.2023.112049 |
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author | Triller, Gianna Vlachou, Evi P. Hashemi, Hamidreza van Straaten, Monique Zeelen, Johan P. Kelemen, Yosip Baehr, Carly Marker, Cheryl L. Ruf, Sandra Svirina, Anna Chandra, Monica Urban, Katharina Gkeka, Anastasia Kruse, Sebastian Baumann, Andreas Miller, Aubry K. Bartel, Marc Pravetoni, Marco Stebbins, C. Erec Papavasiliou, F. Nina Verdi, Joseph P. |
author_facet | Triller, Gianna Vlachou, Evi P. Hashemi, Hamidreza van Straaten, Monique Zeelen, Johan P. Kelemen, Yosip Baehr, Carly Marker, Cheryl L. Ruf, Sandra Svirina, Anna Chandra, Monica Urban, Katharina Gkeka, Anastasia Kruse, Sebastian Baumann, Andreas Miller, Aubry K. Bartel, Marc Pravetoni, Marco Stebbins, C. Erec Papavasiliou, F. Nina Verdi, Joseph P. |
author_sort | Triller, Gianna |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-10387133 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
record_format | MEDLINE/PubMed |
spelling | pubmed-103871332023-10-23 A trypanosome-derived immunotherapeutics platform elicits potent high-affinity antibodies, negating the effects of the synthetic opioid fentanyl Triller, Gianna Vlachou, Evi P. Hashemi, Hamidreza van Straaten, Monique Zeelen, Johan P. Kelemen, Yosip Baehr, Carly Marker, Cheryl L. Ruf, Sandra Svirina, Anna Chandra, Monica Urban, Katharina Gkeka, Anastasia Kruse, Sebastian Baumann, Andreas Miller, Aubry K. Bartel, Marc Pravetoni, Marco Stebbins, C. Erec Papavasiliou, F. Nina Verdi, Joseph P. Cell Rep Article 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. 2023-02-28 2023-01-30 /pmc/articles/PMC10387133/ /pubmed/36719797 http://dx.doi.org/10.1016/j.celrep.2023.112049 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) ). |
spellingShingle | Article Triller, Gianna Vlachou, Evi P. Hashemi, Hamidreza van Straaten, Monique Zeelen, Johan P. Kelemen, Yosip Baehr, Carly Marker, Cheryl L. Ruf, Sandra Svirina, Anna Chandra, Monica Urban, Katharina Gkeka, Anastasia Kruse, Sebastian Baumann, Andreas Miller, Aubry K. Bartel, Marc Pravetoni, Marco Stebbins, C. Erec Papavasiliou, F. Nina Verdi, Joseph P. A trypanosome-derived immunotherapeutics platform elicits potent high-affinity antibodies, negating the effects of the synthetic opioid fentanyl |
title | A trypanosome-derived immunotherapeutics platform elicits potent high-affinity antibodies, negating the effects of the synthetic opioid fentanyl |
title_full | A trypanosome-derived immunotherapeutics platform elicits potent high-affinity antibodies, negating the effects of the synthetic opioid fentanyl |
title_fullStr | A trypanosome-derived immunotherapeutics platform elicits potent high-affinity antibodies, negating the effects of the synthetic opioid fentanyl |
title_full_unstemmed | A trypanosome-derived immunotherapeutics platform elicits potent high-affinity antibodies, negating the effects of the synthetic opioid fentanyl |
title_short | A trypanosome-derived immunotherapeutics platform elicits potent high-affinity antibodies, negating the effects of the synthetic opioid fentanyl |
title_sort | trypanosome-derived immunotherapeutics platform elicits potent high-affinity antibodies, negating the effects of the synthetic opioid fentanyl |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10387133/ https://www.ncbi.nlm.nih.gov/pubmed/36719797 http://dx.doi.org/10.1016/j.celrep.2023.112049 |
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