Memory B cell repertoire for recognition of evolving SARS-CoV-2 spike

Area of Science:

• Immunology
• Virology
• Structural Biology

Background:

• Memory B cells are crucial for long-term immunity against viral infections like SARS-CoV-2.
• The ability of antibodies generated from initial infection to neutralize antigenically drifted variants remains incompletely understood.

Approach:

• Monoclonal antibodies (mAbs) encoded by memory B cell receptors were analyzed from 19 individuals who recovered from COVID-19.
• Structural analysis of mAb-SARS-CoV-2 spike (S) protein complexes identified key binding epitopes.
• mAb competition groups were defined and correlated with cross-reactivity, neutralization potency, and antibody signatures.

Key Points:

• Seven major mAb competition groups targeting recurrent epitopes on the SARS-CoV-2 S protein were identified.
• Antibody groups showed varying degrees of cross-reactivity and neutralization potency against different SARS-CoV-2 variants.
• Differential binding to S variants by mAbs targeting the original isolate highlighted the importance of diverse recognition.

Conclusions:

• A comprehensive atlas of the S-specific memory B cell repertoire was created.
• The study illustrates how antibody recognition properties contribute to robustness against emerging SARS-CoV-2 variants.