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Fast-Track Discovery of SARS-CoV-2-Neutralizing Antibodies from Human B Cells by Direct Functional Screening.
- Source :
-
Viruses [Viruses] 2024 Feb 22; Vol. 16 (3). Date of Electronic Publication: 2024 Feb 22. - Publication Year :
- 2024
-
Abstract
- As the COVID-19 pandemic revealed, rapid development of vaccines and therapeutic antibodies are crucial to guarantee a quick return to the status quo of society. In early 2020, we deployed our droplet microfluidic single-cell-based platform DROPZYLLA <superscript>®</superscript> for the generation of cognate antibody repertoires of convalescent COVID-19 donors. Discovery of SARS-CoV-2-specific antibodies was performed upon display of antibodies on the surface of HEK293T cells by antigen-specific sorting using binding to the SARS-CoV-2 spike and absence of binding to huACE2 as the sort criteria. This efficiently yielded antibodies within 3-6 weeks, of which up to 100% were neutralizing. One of these, MTX-COVAB, displaying low picomolar neutralization IC50 of SARS-CoV-2 and with a neutralization potency on par with the Regeneron antibodies, was selected for GMP manufacturing and clinical development in June 2020. MTX-COVAB showed strong efficacy in vivo and neutralized all identified clinically relevant variants of SARS-CoV-2 at the time of its selection. MTX-COVAB completed GMP manufacturing by the end of 2020, but clinical development was stopped when the Omicron variant emerged, a variant that proved to be detrimental to all monoclonal antibodies already approved. The present study describes the capabilities of the DROPZYLLA <superscript>®</superscript> platform to identify antibodies of high virus-neutralizing capacity rapidly and directly.
Details
- Language :
- English
- ISSN :
- 1999-4915
- Volume :
- 16
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Viruses
- Publication Type :
- Academic Journal
- Accession number :
- 38543705
- Full Text :
- https://doi.org/10.3390/v16030339