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000241137 041__ $$aEnglish
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000241137 1001_ $$0P:(DE-He78)b22859d95abd0c9334442dfafdf9dc01$$aTriller, Gianna$$b0$$eFirst author$$udkfz
000241137 245__ $$aA trypanosome-derived immunotherapeutics platform elicits potent high-affinity antibodies, negating the effects of the synthetic opioid fentanyl.
000241137 260__ $$a[New York, NY]$$bElsevier$$c2023
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000241137 520__ $$aPoorly immunogenic small molecules pose challenges for the production of clinically efficacious vaccines and antibodies. To address this, we generate an immunization platform derived from the immunogenic surface coat of the African trypanosome. Through sortase-based conjugation of the target molecules to the variant surface glycoprotein (VSG) of the trypanosome surface coat, we develop VSG-immunogen array by sortase tagging (VAST). VAST elicits antigen-specific memory B cells and antibodies in a murine model after deploying the poorly immunogenic molecule fentanyl as a proof of concept. We also develop a single-cell RNA sequencing (RNA-seq)-based computational method that synergizes with VAST to specifically identify memory B cell-encoded antibodies. All computationally selected antibodies bind to fentanyl with picomolar affinity. Moreover, these antibodies protect mice from fentanyl effects after passive immunization, demonstrating the ability of these two coupled technologies to elicit therapeutic antibodies to challenging immunogens.
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000241137 650_7 $$2Other$$aCP: Immunology
000241137 650_7 $$2Other$$aTrypanosoma brucei
000241137 650_7 $$2Other$$aantibody repertoire analysis
000241137 650_7 $$2Other$$afentanyl
000241137 650_7 $$2Other$$ahumoral immunity
000241137 650_7 $$2Other$$aimmunological memory
000241137 650_7 $$2Other$$aopioid overdose
000241137 650_7 $$2Other$$asortase
000241137 650_7 $$2Other$$avariant surface glycoprotein
000241137 7001_ $$0P:(DE-HGF)0$$aVlachou, Evi P$$b1
000241137 7001_ $$0P:(DE-He78)8a54ae86df2d4a9f54a26e80554e806e$$aHashemi, Hamidreza$$b2
000241137 7001_ $$0P:(DE-He78)604bb0ebdb4e4aa550668663597c9ec8$$avan Straaten, Monique$$b3$$udkfz
000241137 7001_ $$0P:(DE-He78)60be168620c9910e4bb9c2b99d8db56f$$aZeelen, Johan P$$b4$$udkfz
000241137 7001_ $$aKelemen, Yosip$$b5
000241137 7001_ $$aBaehr, Carly$$b6
000241137 7001_ $$aMarker, Cheryl L$$b7
000241137 7001_ $$0P:(DE-He78)987a16a93296d4a043a1b2337d224b53$$aRuf, Sandra$$b8$$udkfz
000241137 7001_ $$0P:(DE-He78)eba50148f2b8e408c7df5d753c698e3a$$aSvirina, Anna$$b9$$udkfz
000241137 7001_ $$0P:(DE-He78)97b2ee6c4015e70e559ff4b9ab637e72$$aChandra, Monica$$b10$$udkfz
000241137 7001_ $$0P:(DE-He78)9cafc6ecff7e1f32c9d4644c841740cb$$aUrban, Katharina$$b11$$udkfz
000241137 7001_ $$0P:(DE-He78)2860863e19e5f3ec9efeced72d895714$$aGkeka, Anastasia$$b12$$udkfz
000241137 7001_ $$aKruse, Sebastian$$b13
000241137 7001_ $$0P:(DE-He78)732ee924fba787fd2f9235b0a960ca53$$aBaumann, Andreas$$b14
000241137 7001_ $$0P:(DE-He78)f0af962ddbc82430e947390b2f3f6e49$$aMiller, Aubry K$$b15$$udkfz
000241137 7001_ $$aBartel, Marc$$b16
000241137 7001_ $$aPravetoni, Marco$$b17
000241137 7001_ $$0P:(DE-He78)3e1497ece09f8d2c69efc8b106a08f2b$$aStebbins, C Erec$$b18$$udkfz
000241137 7001_ $$0P:(DE-He78)79dbda58d51b613a0a421f579d2dfed3$$aPapavasiliou, F Nina$$b19$$udkfz
000241137 7001_ $$0P:(DE-He78)e13953968ed53b7fcae1139ac9ea7583$$aVerdi, Joseph Peter$$b20$$eLast author$$udkfz
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