Publication date: Jul 04, 2025
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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Semantics
| Type | Source | Name |
|---|---|---|
| disease | IDO | cell |
| disease | MESH | infection |
| disease | IDO | intervention |
| pathway | REACTOME | Metabolism |
| pathway | REACTOME | Adaptive Immune System |
| disease | IDO | process |
| drug | DRUGBANK | Methylergometrine |
| disease | IDO | blood |
| disease | MESH | SARS CoV 2 infection |
| drug | DRUGBANK | Hexocyclium |
| disease | MESH | breakthrough infection |
| disease | MESH | reinfection |
| disease | MESH | asymptomatic infection |
| disease | IDO | assay |
| drug | DRUGBANK | Proline |
| drug | DRUGBANK | Esomeprazole |
| drug | DRUGBANK | Hyaluronic acid |
| disease | MESH | convalescence |
| disease | IDO | history |
| drug | DRUGBANK | Trestolone |
| drug | DRUGBANK | Guanosine |
| disease | IDO | host |
| drug | DRUGBANK | Inosine |
| drug | DRUGBANK | Efavirenz |
| disease | IDO | reagent |
| drug | DRUGBANK | Immune Globulin Human |
| drug | DRUGBANK | Streptomycin |
| drug | DRUGBANK | Flunarizine |
| drug | DRUGBANK | Coenzyme M |
| drug | DRUGBANK | Sodium lauryl sulfate |
| drug | DRUGBANK | Gold |
| drug | DRUGBANK | Titanium |