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TitleA rare B cell clonotype imprinted by ancestral SARS-CoV-2 develops cross-sarbecovirus neutralization in immune recalls.
Journal, issue, pagesCell Rep, Vol. 44, Issue 7, Page 115964, Year 2025
Publish dateJul 4, 2025
AuthorsXixian Chen / Ling Li / Ruiping Du / Zuowei Wang / Yunjian Li / Yi Sun / Rongrong Qin / Hualong Feng / Lin Hu / Xuanyi Chen / Maosheng Lu / Xueyan Huang / Haibo Wang / Liwei Jiang / Teng Zuo /
PubMed AbstractThe 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 ...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.
External linksCell Rep / PubMed:40616841
MethodsEM (single particle)
Resolution3.03 - 3.17 Å
Structure data

64581

9uxd

EMDB-64581, PDB-9uxd:
SARS-CoV2 Spike protein with Fab fragment antibody KXD355,state1
Method: EM (single particle) / Resolution: 3.03 Å

64582

9uxe

EMDB-64582, PDB-9uxe:
SARS-CoV2 Spike protein with Fab fragment antibody KXD355,state2
Method: EM (single particle) / Resolution: 3.17 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

Source
  • homo sapiens (human)
  • severe acute respiratory syndrome coronavirus 2
KeywordsVIRAL PROTEIN/IMMUNE SYSTEM / spike / antibody / VIRAL PROTEIN-IMMUNE SYSTEM complex

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