Abstract
The molecular composition and binding epitopes of the immunoglobulin G (IgG) antibodies that circulate in blood plasma after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are unknown. Proteomic deconvolution of the IgG repertoire to the spike glycoprotein in convalescent subjects revealed that the response is directed predominantly (>80%) against epitopes residing outside the receptor binding domain (RBD). In one subject, just four IgG lineages accounted for 93.5% of the response, including an amino (N)-terminal domain (NTD)-directed antibody that was protective against lethal viral challenge. Genetic, structural, and functional characterization of a multidonor class of “public” antibodies revealed an NTD epitope that is recurrently mutated among emerging SARS-CoV-2 variants of concern. These data show that “public” NTD-directed and other non-RBD plasma antibodies are prevalent and have implications for SARS-CoV-2 protection and antibody escape.
Original language | English (US) |
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Pages (from-to) | 1108-1112 |
Number of pages | 5 |
Journal | Science |
Volume | 372 |
Issue number | 6546 |
DOIs | |
State | Published - Jun 4 2021 |
Keywords
- Animals
- Antibodies, Monoclonal/blood
- Antibodies, Neutralizing/blood
- Antibodies, Viral/blood
- Antibody Affinity
- COVID-19/immunology
- Epitopes/immunology
- Humans
- Immune Evasion
- Immunoglobulin G/blood
- Immunoglobulin Heavy Chains/immunology
- Immunoglobulin Variable Region/immunology
- Mice
- Mice, Inbred BALB C
- Mutation
- Protein Domains
- Proteomics
- SARS-CoV-2/genetics
- Spike Glycoprotein, Coronavirus/chemistry
ASJC Scopus subject areas
- General