A rapid cell-free expression and screening platform for antibody discovery.
Andrew C Hunt1,2, Bastian Vögeli1,2, Ahmed O Hassan3
1Department of Chemical and Biological Engineering, Northwestern University, Evanston, IL, 60208, USA.
Nature Communications
|July 3, 2023
Summary
A new cell-free workflow rapidly discovers potent antibodies against SARS-CoV-2, accelerating research and development for future pandemics. This method efficiently evaluates antibody fragments, identifying promising candidates for diagnostics and therapeutics.
Area of Science:
- Biotechnology
- Immunology
- Molecular Biology
Background:
- Antibody discovery is hindered by slow, individual expression and evaluation of antigen-specific antibodies.
- Existing methods for antibody screening are time-consuming, delaying the development of crucial therapeutics and diagnostics.
Purpose of the Study:
- To develop and validate a rapid, cell-free workflow for antibody discovery and characterization.
- To identify potent and neutralizing antibodies targeting the SARS-CoV-2 spike protein.
Main Methods:
- A novel cell-free workflow integrating DNA template generation, cell-free protein synthesis, and binding measurements of antibody fragments.
- Application of the workflow to screen 135 published anti-SARS-CoV-2 antibodies and 119 novel antibodies from immunized mice.
Main Results:
- The cell-free workflow significantly reduces the time for antibody evaluation from weeks to hours.
- Identified the most potent antibodies among previously published SARS-CoV-2 antibodies, including emergency use authorized ones.
- Discovered novel neutralizing antibody candidates, such as SC2-3, effective against all tested SARS-CoV-2 variants of concern.
Conclusions:
- The developed cell-free workflow offers a rapid and efficient approach to antibody discovery and characterization.
- This methodology has the potential to accelerate the development of antibodies for future pandemics and various applications.
- The identified antibodies, including SC2-3, represent valuable candidates for research, diagnostics, and therapeutic interventions against SARS-CoV-2.
