TY - JOUR T1 - Accelerated Antibody Discovery Targeting the SARS-CoV-2 Spike Protein for COVID-19 Therapeutic Potential JF - bioRxiv DO - 10.1101/2021.05.31.446421 SP - 2021.05.31.446421 AU - Tracey E. Mullen AU - Rashed Abdullah AU - Jacqueline Boucher AU - Anna Susi Brousseau AU - Narayan K. Dasuri AU - Noah T. Ditto AU - Andrew M. Doucette AU - Chloe Emery AU - Justin Gabriel AU - Brendan Greamo AU - Ketan S. Patil AU - Kelly Rothenberger AU - Justin Stolte AU - Colby A. Souders Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/05/31/2021.05.31.446421.abstract N2 - Rapid deployment of technologies capable of high-throughput and high-resolution screening is imperative for timely response to viral outbreaks. Risk mitigation in the form of leveraging multiple advanced technologies further increases the likelihood of identifying efficacious treatments in an aggressive timeline. In this study, we describe two parallel, yet distinct, in vivo approaches for accelerated discovery of antibodies targeting the SARS-CoV-2 spike protein. Working with human transgenic Alloy-GK mice, we detail a single B-cell discovery workflow to directly interrogate antibodies secreted from plasma cells for binding specificity and ACE2 receptor blocking activity. Additionally, we describe a concurrent accelerated hybridoma-based workflow utilizing a DiversimAbâ„¢ mouse model for increased diversity. The panel of antibodies isolated from both workflows revealed binding to distinct epitopes with both blocking and non-blocking profiles. Sequence analysis of the resulting lead candidates uncovered additional diversity with the opportunity for straightforward engineering and affinity maturation. By combining in vivo models with advanced integration of screening and selection platforms, lead antibody candidates can be sequenced and fully characterized within one to three months.Competing Interest StatementThe authors have declared no competing interest. ER -