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bioRxiv · 10.64898/2026.01.07.697678

Single-antibody mutational scanning reveals poly-specificity and immune constraints in vaccination responses

Schlotheuber, L. J.·Agersnap, S. N.·Greis, D.·Streuli, A.·Yamauchi, Y.·Eyer, K.
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Abstract

Current repertoire technologies with single-antibody resolution usually assess binding to only one or a few recombinant antigens, neglecting variant diversity of antigens and poly-specificity of antibodies. Here, we introduce a method for analyzing antibody repertoires at single-antibody resolution against a large library of SARS-CoV-2 receptor-binding domain (RBD) variants, enabling the identification and analysis of recognized RBD variants by rare, poly-specific antibodies. This technique provided unique insights into single-antibody binding and escape profiles within a murine immunization model with different RBDs, offering valuable data useful to optimize vaccine design against emerging variants and study antibody poly-specificity.

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Schlotheuber, L. J., Agersnap, S. N., Greis, D., Streuli, A., Yamauchi, Y., Eyer, K.. 2026-01-07. Single-antibody mutational scanning reveals poly-specificity and immune constraints in vaccination responses. https://doi.org/10.64898/2026.01.07.697678

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