High-throughput synthesis and specificity characterization of natively paired influenza hemagglutinin antibodies with oPool+ display

A challenge with current antibody discovery approaches is the laborious process of characterizing antigen-specific B cell receptors (BCRs). It requires cloning and synthesizing antibodies on the basis of those BCRs one at a time, followed by binding characterization using standard laboratory methods. To streamline this process, Ouyang et al. developed oPool+ display, a high-throughput platform for characterizing binding of natively paired antibodies. The authors used influenza hemagglutinin (HA) variants as proof-of-concept antibody targets, showing that they could successfully identify antibodies against HA on the order of days. They validated their method with orthogonal methods, such as ELISA and biolayer interferometry, and then tested two candidates for their ability to neutralize influenza A virus in vivo and in vitro. Although this study is focused on HA-specific antibodies, it lays the groundwork for using oPool+ display to rapidly identify antibodies against a wide range of targets.