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Memory B cell repertoire for recognition of evolving SARS-CoV-2 spike
Pei Tong1, Avneesh Gautam1, Ian W Windsor2
1Department of Medicine, Division of Allergy and Immunology, Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Cell
|August 1, 2021
Summary
Memory B cells generate antibodies against SARS-CoV-2, but variants can escape. Some antibodies remain effective, highlighting their importance for durable protection against evolving viruses like SARS-CoV-2.
Area of Science:
- Immunology
- Virology
- Structural Biology
Background:
- Memory B cells are crucial for long-term immunity against pathogens like SARS-CoV-2.
- The ability of memory B cell-generated antibodies to neutralize antigenically drifted SARS-CoV-2 variants remains incompletely understood.
Purpose of the Study:
- To characterize the SARS-CoV-2-specific memory B cell repertoire.
- To investigate the cross-reactivity, neutralization potency, and structural basis of antibodies targeting SARS-CoV-2 spike (S) protein variants.
Main Methods:
- Analysis of memory B cell receptor-encoded antibodies from 19 COVID-19 convalescent subjects.
- Structural determination of antibody-S complexes.
- Assessment of antibody binding affinity, cross-reactivity, and neutralization potency against SARS-CoV-2 variants.
Main Results:
- Seven major antibody competition groups targeting recurrent epitopes on the SARS-CoV-2 S protein were identified.
- Antibody group assignment correlated with cross-reactivity, neutralization breadth, and convergent antibody signatures.
- While some SARS-CoV-2 variants of concern escaped neutralization by potent antibodies, others retained binding affinity, indicating conserved protective responses.
Conclusions:
- The study provides a comprehensive atlas of the S-specific memory B cell repertoire.
- Antibodies generated during primary SARS-CoV-2 infection contribute to durable protection against evolving viral variants.
- Understanding these antibody features can inform strategies against future viral threats.
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