Journal
PROTEIN ENGINEERING DESIGN & SELECTION
Volume 28, Issue 10, Pages 379-383Publisher
OXFORD UNIV PRESS
DOI: 10.1093/protein/gzv039
Keywords
next-generation DNA sequencing; phage display; serum albumin; single-domain antibody; VHH
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Antibodies that cross-react with multiple isoforms or homologue of a given protein are often desirable, especially in therapeutic applications. Here, we report the identification of several unique, clonally unrelated, single-domain antibodies (sdAbs) that bind to multiple serum albumin orthologues (human, rhesus, rat and mouse) with low-to-medium nanomolar affinity from a llama immunized only with human serum albumin. Using single-round panning of a phage-displayed sdAb library against serum albumins and next-generation DNA sequencing, we were able to predict patterns of sdAb reactivity to the albumins of different species with similar to 90% accuracy. We expect this strategy to be generally applicable for identifying cross-reactive sdAbs, particularly when these exist at low frequency and/or are poorly enriched by panning. Moreover, the sdAbs identified here are of potential interest for serum half-life extension of biologics.
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