A rare B cell clonotype imprinted by ancestral SARS-CoV-2 develops cross-sarbecovirus neutralization in immune recalls
Summary: The ultimate potential of B cells imprinted by ancestral SARS-CoV-2 in developing neutralizing breadth and potency remains to be explored. Here, we longitudinally tracked B cells that recognize the wild-type spike in two individuals who were repeatedly infected by Omicron variants after rec...
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| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-07-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124725007351 |
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| Summary: | Summary: The ultimate potential of B cells imprinted by ancestral SARS-CoV-2 in developing neutralizing breadth and potency remains to be explored. Here, we longitudinally tracked B cells that recognize the wild-type spike in two individuals who were repeatedly infected by Omicron variants after receiving prototype mRNA vaccines. Functional and genetic analysis of 632 monoclonal antibodies (mAbs) from those B cells reveals that mAbs cloned after a second infection have dramatically enhanced neutralizing breadth and potency due to immune recalls. Among the eleven mAbs that broadly neutralize SARS-CoV-2 variants from the wild type to KP.3, five mAbs are classified into public clonotypes encoded by IGHV3-53 or IGHV3-66, whereas the rest belong to a rare clonotype encoded by IGHV3-74. Notably, IGHV3-74 mAbs can also potently neutralize other sarbecoviruses by targeting a non-dominant epitope partially overlapping with receptor-binding domain (RBD)-3 and RBD-5. These results support that ancestral SARS-CoV-2 immune imprinting can be harnessed in developing pan-SARS-CoV-2 and even cross-sarbecovirus vaccines. |
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| ISSN: | 2211-1247 |