High-throughput specificity profiling of antibody libraries using ribosome display and microfluidics.

IF 4.3 Q1 BIOCHEMICAL RESEARCH METHODS Cell Reports Methods Pub Date : 2024-12-16 DOI:10.1016/j.crmeth.2024.100934

Ellen K Wagner, Kyle P Carter, Yoong Wearn Lim, Geeyun Jenny Chau, Alexis Enstrom, Nicholas P Wayham, Jessica-Mae Hanners, Chiann-Ling C Yeh, Marc Fouet, Jackson Leong, Adam S Adler, Jan Fredrik Simons

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Abstract

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.

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