A rapid cell-free expression and screening platform for antibody discovery
Abstract
Antibody discovery is bottlenecked by the individual expression and evaluation of antigen-specific hits. Here, we address this bottleneck by developing a workflow combining cell-free DNA template generation, cell-free protein synthesis, and binding measurements of antibody fragments in a process that takes hours rather than weeks. We apply this workflow to evaluate 135 previously published antibodies targeting the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), including all 8 antibodies previously granted emergency use authorization for coronavirus disease 2019 (COVID-19), and demonstrate identification of the most potent antibodies. We also evaluate 119 anti-SARS-CoV-2 antibodies from a mouse immunized with the SARS-CoV-2 spike protein and identify neutralizing antibody candidates, including the antibody SC2-3, which binds the SARS-CoV-2 spike protein of all tested variants of concern. We expect that our cell-free workflow will accelerate the discovery and characterization of antibodies for future pandemics and for research, diagnostic, and therapeutic applications more broadly.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jul 03, 2023
- Source ID
- 10.1038/s41467-023-38965-w
Entities
People
- Ahmed O. Hassan
- Andrew C Hunt
- Antje Krüger
- Ashty S Karim
- Bastian Vögeli
- Danielle J. Yoesep
- Laura Guerrero
- Madison A. DeWinter
- Michael C Jewett
- Michael S. Diamond
- Weston Kightlinger
Organizations
- Defense Threat Reduction Agency
- National Institutes of Health
- United States Department of Defense