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

ABSTRACT: Antibody discovery is crucial for developing therapeutics and vaccines and for understanding adaptive immunity. However, the lack of approaches to synthesize antibodies with defined sequences in a high-throughput manner represents a major bottleneck in antibody discovery. Here, we present oPool⁺ display, a high-throughput cell-free platform that combined oligo pool synthesis and mRNA display to rapidly construct and characterize hundreds to thousands of natively paired antibodies in parallel. As a proof of concept, we applied oPool⁺ display to probe the binding specificity of more than 300 uncommon influenza hemagglutinin-specific antibodies against nine hemagglutinin variants through 16 screens. More than 5000 binding tests were performed in 3 to 5 days of hands-on t

SUBMITTER: Ouyang WO 

PROVIDER: S-EPMC12422562 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature