Accelerated antibody discovery targeting the SARS-CoV-2 spike protein for COVID-19 therapeutic potential
| Autor: | Chloe Emery, Jacqueline Boucher, Ketan S. Patil, Anna Susi Brousseau, Tracey E Mullen, Kelly Rothenberger, Justin Stolte, Brendan Greamo, Andrew M Doucette, Narayan K Dasuri, Colby A. Souders, Noah T Ditto, Justin Gabriel, Rashed Abdullah |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
AcademicSubjects/SCI01030
beacon biology Sequence analysis Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Transgene Immunology epitope binning Computational biology Epitope Affinity maturation therapeutic In vivo Epitope binning biology.protein Immunology and Allergy single B cell carterra neutralizing antibodies Original Research Article Antibody human antibody Binding selectivity COVID |
| Zdroj: | Antibody Therapeutics |
| ISSN: | 2516-4236 |
| Popis: | Background 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 aggressive timelines. Methods In this study, we describe two parallel, yet distinct, in vivo approaches for accelerated discovery of antibodies targeting the severe acute respiratory syndrome coronavirus-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 DiversimAb™ mouse model for increased diversity. Results 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. Conclusions 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. |
| Databáze: | OpenAIRE |
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