We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Fast-Track Discovery of SARS-CoV-2-Neutralizing Antibodies from Human B Cells by Direct Functional Screening.
- Authors
Hillenbrand, Matthias; Esslinger, Christoph; Seidenberg, Jemima; Weber, Marcel; Zingg, Andreas; Townsend, Catherine; Eicher, Barbara; Rutkauskaite, Justina; Riese, Peggy; Guzman, Carlos A.; Fischer, Karsten; Schmitt, Simone
- 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® 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® platform to identify antibodies of high virus-neutralizing capacity rapidly and directly.
- Subjects
B cells; MONOCLONAL antibodies; SARS-CoV-2 Omicron variant; IMMUNOGLOBULINS; SARS-CoV-2; VACCINE development
- Publication
Viruses (1999-4915), 2024, Vol 16, Issue 3, p339
- ISSN
1999-4915
- Publication type
Article
- DOI
10.3390/v16030339