Rapid discovery of monoclonal antibodies by microfluidics-enabled FACS of single pathogen-specific antibody-secreting cells

Monoclonal antibodies are increasingly used to prevent and treat viral infections and are pivotal in pandemic response efforts. Antibody-secreting cells (ASCs; plasma cells and plasmablasts) are an excellent source of high-affinity antibodies with therapeutic potential. Current methods to study anti...

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Published in:Nature biotechnology 2024-08
Main Authors: Fischer, Katrin, Lulla, Aleksei, So, Tsz Y, Pereyra-Gerber, Pehuén, Raybould, Matthew I J, Kohler, Timo N, Yam-Puc, Juan Carlos, Kaminski, Tomasz S, Hughes, Robert, Pyeatt, Gwendolyn L, Leiss-Maier, Florian, Brear, Paul, Matheson, Nicholas J, Deane, Charlotte M, Hyvönen, Marko, Thaventhiran, James E D, Hollfelder, Florian
Format: Article
Language:English
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Summary:Monoclonal antibodies are increasingly used to prevent and treat viral infections and are pivotal in pandemic response efforts. Antibody-secreting cells (ASCs; plasma cells and plasmablasts) are an excellent source of high-affinity antibodies with therapeutic potential. Current methods to study antigen-specific ASCs either have low throughput, require expensive and labor-intensive screening or are technically demanding and therefore not widely accessible. Here we present a straightforward technology for the rapid discovery of monoclonal antibodies from ASCs. Our approach combines microfluidic encapsulation of single cells into an antibody capture hydrogel with antigen bait sorting by conventional flow cytometry. With our technology, we screened millions of mouse and human ASCs and obtained monoclonal antibodies against severe acute respiratory syndrome coronavirus 2 with high affinity (
ISSN:1546-1696
1546-1696
DOI:10.1038/s41587-024-02346-5