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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...

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Main Authors: Triller, Gianna (Author) , Vlachou, Evi P. (Author) , Hashemi, Hamidreza (Author) , van Straaten, Monique (Author) , Zeelen, Johan P. (Author) , Kelemen, Yosip (Author) , Baehr, Carly (Author) , Marker, Cheryl L. (Author) , Ruf, Sandra (Author) , Svirina, Anna (Author) , Chandra, Monica (Author) , Urban, Katharina (Author) , Gkeka, Anastasia (Author) , Kruse, Sebastian (Author) , Baumann, Andreas (Author) , Miller, Aubry K. (Author) , Bartel, Marc (Author) , Pravetoni, Marco (Author) , Stebbins, Erec (Author) , Papavasiliou, Nina (Author) , Verdi, Joseph P. (Author)
Format: Article (Journal)
Language:English
Published: 30 January 2023
In: Cell reports
Year: 2023, Volume: 42, Issue: 2, Pages: 1-28
ISSN:2211-1247
DOI:10.1016/j.celrep.2023.112049
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.celrep.2023.112049
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S2211124723000608
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Author Notes:Gianna Triller, Evi P. Vlachou, Hamidreza Hashemi, Monique van Straaten, Johan P. Zeelen, Yosip Kelemen, Carly Baehr, Cheryl L. Marker, Sandra Ruf, Anna Svirina, Monica Chandra, Katharina Urban, Anastasia Gkeka, Sebastian Kruse, Andreas Baumann, Aubry K. Miller, Marc Bartel, Marco Pravetoni, C. Erec Stebbins, F. Nina Papavasiliou, and Joseph P. Verdi
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Summary: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.
Item Description:Gesehen am 21.03.2023
Physical Description:Online Resource
ISSN:2211-1247
DOI:10.1016/j.celrep.2023.112049

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