High-throughput specificity profiling of antibody libraries using ribosome display and microfluidics.
Autor: | Wagner EK; GigaGen, Inc. (a Grifols company), San Carlos, CA, USA. Electronic address: ellen.wagner@grifols.com., Carter KP; GigaGen, Inc. (a Grifols company), San Carlos, CA, USA., Lim YW; GigaGen, Inc. (a Grifols company), San Carlos, CA, USA., Chau GJ; GigaGen, Inc. (a Grifols company), San Carlos, CA, USA., Enstrom A; GigaGen, Inc. (a Grifols company), San Carlos, CA, USA., Wayham NP; GigaGen, Inc. (a Grifols company), San Carlos, CA, USA., Hanners JM; GigaGen, Inc. (a Grifols company), San Carlos, CA, USA., Yeh CC; GigaGen, Inc. (a Grifols company), San Carlos, CA, USA., Fouet M; GigaGen, Inc. (a Grifols company), San Carlos, CA, USA., Leong J; GigaGen, Inc. (a Grifols company), San Carlos, CA, USA., Adler AS; GigaGen, Inc. (a Grifols company), San Carlos, CA, USA., Simons JF; GigaGen, Inc. (a Grifols company), San Carlos, CA, USA. Electronic address: jan.simons@grifols.com. |
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Jazyk: | angličtina |
Zdroj: | Cell reports methods [Cell Rep Methods] 2024 Dec 16; Vol. 4 (12), pp. 100934. |
DOI: | 10.1016/j.crmeth.2024.100934 |
Abstrakt: | In this work, we developed PolyMap (polyclonal mapping), a high-throughput method for mapping protein-protein interactions. We demonstrated the mapping of thousands of antigen-antibody interactions between diverse antibody libraries isolated from convalescent and vaccinated COVID-19 donors and a set of clinically relevant SARS-CoV-2 spike variants. We identified over 150 antibodies with a variety of distinctive binding patterns toward the antigen variants and found a broader binding profile, including targeting of the Omicron variant, in the antibody repertoires of more recent donors. We then used these data to select mixtures of a small number of clones with complementary reactivity that together provide strong potency and broad neutralization. PolyMap is a generalizable platform that can be used for one-pot epitope mapping, immune repertoire profiling, and therapeutic design and, in the future, could be expanded to other families of interacting proteins. Competing Interests: Declaration of interests All authors are current or past employees of GigaGen, Inc. (a Grifols company). E.K.W., K.P.C., Y.W.L., A.S.A., and J.F.S. are inventors on a patent application related to the PolyMap platform. (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.) |
Databáze: | MEDLINE |
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