TY  - JOUR
AU  - Triller, Gianna
AU  - Vlachou, Evi P
AU  - Hashemi, Hamidreza
AU  - van Straaten, Monique
AU  - Zeelen, Johan P
AU  - Kelemen, Yosip
AU  - Baehr, Carly
AU  - Marker, Cheryl L
AU  - Ruf, Sandra
AU  - Svirina, Anna
AU  - Chandra, Monica
AU  - Urban, Katharina
AU  - Gkeka, Anastasia
AU  - Kruse, Sebastian
AU  - Baumann, Andreas
AU  - Miller, Aubry K
AU  - Bartel, Marc
AU  - Pravetoni, Marco
AU  - Stebbins, C Erec
AU  - Papavasiliou, F Nina
AU  - Verdi, Joseph Peter
TI  - A trypanosome-derived immunotherapeutics platform elicits potent high-affinity antibodies, negating the effects of the synthetic opioid fentanyl.
JO  - Cell reports
VL  - 42
IS  - 2
SN  - 2211-1247
CY  - [New York, NY]
PB  - Elsevier
M1  - DKFZ-2023-00250
SP  - 112049
PY  - 2023
N1  - #EA:D150#LA:D150#
AB  - 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.
KW  - CP: Immunology (Other)
KW  - Trypanosoma brucei (Other)
KW  - antibody repertoire analysis (Other)
KW  - fentanyl (Other)
KW  - humoral immunity (Other)
KW  - immunological memory (Other)
KW  - opioid overdose (Other)
KW  - sortase (Other)
KW  - variant surface glycoprotein (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:36719797
DO  - DOI:10.1016/j.celrep.2023.112049
UR  - https://inrepo02.dkfz.de/record/241137
ER  -