9UXE

SARS-CoV2 Spike protein with Fab fragment antibody KXD355,state2

Summary for 9UXE

• Entry DOI: 10.2210/pdb9uxe/pdb
• EMDB information: 64582
• Descriptor: Spike glycoprotein, Antibody KXD355, heavy chain, Antibody KXD355, light chain, ... (6 entities in total)
• Functional Keywords: spike, antibody, viral protein/immune system, viral protein-immune system complex
• Biological source: Severe acute respiratory syndrome coronavirus 2; More
• Total number of polymer chains: 9
• Total formula weight: 578994.78

Authors

Wang, H. (deposition date: 2025-05-13, release date: 2025-07-16)

Primary citation

Chen, X.,Li, L.,Du, R.,Wang, Z.,Li, Y.,Sun, Y.,Qin, R.,Feng, H.,Hu, L.,Chen, X.,Lu, M.,Huang, X.,Wang, H.,Jiang, L.,Zuo, T.
A rare B cell clonotype imprinted by ancestral SARS-CoV-2 develops cross-sarbecovirus neutralization in immune recalls.
Cell Rep, 44:115964-115964, 2025

PubMed Abstract: 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.

PubMed: 40616841
DOI: 10.1016/j.celrep.2025.115964

Experimental method

ELECTRON MICROSCOPY (3.17 Å)