Cross-Reactive SARS-CoV-2 Neutralizing Antibodies From Deep Mining of Early Patient Responses
Open Access
- 15 June 2021
- journal article
- research article
- Published by Frontiers Media SA in Frontiers in Immunology
- Vol. 12, 678570
- https://doi.org/10.3389/fimmu.2021.678570
Abstract
Passive immunization using monoclonal antibodies will play a vital role in the fight against COVID-19. The recent emergence of viral variants with reduced sensitivity to some current antibodies and vaccines highlights the importance of broad cross-reactivity. This study describes deep-mining of the antibody repertoires of hospitalized COVID-19 patients using phage display technology and B cell receptor (BCR) repertoire sequencing to isolate neutralizing antibodies and gain insights into the early antibody response. This comprehensive discovery approach has yielded a panel of potent neutralizing antibodies which bind distinct viral epitopes including epitopes conserved in SARS-CoV-1. Structural determination of a non-ACE2 receptor blocking antibody reveals a previously undescribed binding epitope, which is unlikely to be affected by the mutations in any of the recently reported major viral variants including B.1.1.7 (from the UK), B.1.351 (from South Africa) and B.1.1.28 (from Brazil). Finally, by combining sequences of the RBD binding and neutralizing antibodies with the B cell receptor repertoire sequencing, we also describe a highly convergent early antibody response. Similar IgM-derived sequences occur within this study group and also within patient responses described by multiple independent studies published previously.This publication has 54 references indexed in Scilit:
- IgBLAST: an immunoglobulin variable domain sequence analysis toolNucleic Acids Research, 2013
- Sequence and Structural Convergence of Broad and Potent HIV Antibodies That Mimic CD4 BindingScience, 2011
- Overview of theCCP4 suite and current developmentsActa crystallographica. Section D, Structural biology, 2011
- Generating a panel of highly specific antibodies to 20 human SH2 domains by phage display"Protein Engineering, Design and Selection", 2010
- Integration, scaling, space-group assignment and post-refinementActa crystallographica. Section D, Structural biology, 2010
- PDB_REDO: automated re-refinement of X-ray structure models in the PDBJournal of Applied Crystallography, 2009
- Application of phage display to high throughput antibody generation and characterizationGenome Biology, 2007
- Coot: model-building tools for molecular graphicsActa crystallographica. Section D, Structural biology, 2004
- Refinement of Macromolecular Structures by the Maximum-Likelihood MethodActa crystallographica. Section D, Structural biology, 1997
- Human Antibodies with Sub-nanomolar Affinities Isolated from a Large Non-immunized Phage Display LibraryNature Biotechnology, 1996