High-Throughput Antibody Neutralization Screening in Massively Parallel Droplet Arrays

Gutierrez-Gonzalez, M.; Fahad, A. S.; Delley, C. L.; Chung, C.-Y.; Jin, S.; Boyle, N.; Oliveira de Souza, M.; Pirhanov, A.; Galvez, N. M. S.; Franca, C. T.; Marglous, S.; Bhagat, E.; Vincent, D.; Neumeier, D.; Cao, Y.; Doria-Rose, N.; Reddy, S. T.; Schmidt, A. G.; Balazs, A. B.; Abate, A. R.; DeKosky, B. J.

doi:10.1101/2025.01.31.635965

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bioRxiv · 10.1101/2025.01.31.635965

High-Throughput Antibody Neutralization Screening in Massively Parallel Droplet Arrays

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Abstract

Neutralizing antibodies provide rapid immune defense against infectious diseases, but are difficult to discover at scale because neutralization assays require live reporter cells and soluble monoclonal antibodies. Here we report Droplet Reporter Cell Testing for Neutralization (DrReCT-Neutralization) to screen antibody gene libraries for their ability to neutralize viral infections. We established the necessary engineered cell lines and validated the DrReCT screening platform using synthetic oligoclonal libraries, followed by an example discovery campaign that demonstrated scalable functional antibody data collection against viral diseases.

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Gutierrez-Gonzalez, M., Fahad, A. S., Delley, C. L., Chung, C.-Y., Jin, S., Boyle, N., Oliveira de Souza, M., Pirhanov, A., Galvez, N. M. S., Franca, C. T., Marglous, S., Bhagat, E., Vincent, D., Neumeier, D., Cao, Y., Doria-Rose, N., Reddy, S. T., Schmidt, A. G., Balazs, A. B., Abate, A. R., DeKosky, B. J.. 2025-02-04. High-Throughput Antibody Neutralization Screening in Massively Parallel Droplet Arrays. https://doi.org/10.1101/2025.01.31.635965

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