8XXW

Fab M2-7 complexed with SARS-Cov2 RBD and human ACE2

Summary for 8XXW

• Entry DOI: 10.2210/pdb8xxw/pdb
• EMDB information: 38763
• Descriptor: Processed angiotensin-converting enzyme 2, Spike protein S1, M2-7-Heavy chain, ... (6 entities in total)
• Functional Keywords: antibody viral protein complex, immune system/viral protein, antiviral protein, antiviral protein-immune system complex, antiviral protein/immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 4
• Total formula weight: 113800.82

Authors

Liu, C.,Xie, Y. (deposition date: 2024-01-19, release date: 2024-06-19, Last modification date: 2024-11-20)

Primary citation

Liu, C.,Xu, S.,Zheng, Y.,Xie, Y.,Xu, K.,Chai, Y.,Luo, T.,Dai, L.,Gao, G.F.
Mosaic RBD nanoparticle elicits immunodominant antibody responses across sarbecoviruses.
Cell Rep, 43:114235-114235, 2024

PubMed Abstract: Nanoparticle vaccines displaying mosaic receptor-binding domains (RBDs) or spike (S) from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or other sarbecoviruses are used in preparedness against potential zoonotic outbreaks. Here, we describe a self-assembling nanoparticle using lumazine synthase (LuS) as the scaffold to display RBDs from different sarbecoviruses. Mosaic nanoparticles induce sarbecovirus cross-neutralizing antibodies comparable to a nanoparticle cocktail. We find mosaic nanoparticles elicit a B cell receptor repertoire using an immunodominant germline gene pair of IGHV14-3:IGKV14-111. Most of the tested IGHV14-3:IGKV14-111 monoclonal antibodies (mAbs) are broadly cross-reactive to clade 1a, 1b, and 3 sarbecoviruses. Using mAb competition and cryo-electron microscopy, we determine that a representative IGHV14-3:IGKV14-111 mAb, M2-7, binds to a conserved epitope on the RBD, largely overlapping with the pan-sarbecovirus mAb S2H97. This suggests mosaic nanoparticles expand B cell recognition of the common epitopes shared by different clades of sarbecoviruses. These results provide immunological insights into the cross-reactive responses elicited by mosaic nanoparticles against sarbecoviruses.

PubMed: 38748880
DOI: 10.1016/j.celrep.2024.114235

Experimental method

ELECTRON MICROSCOPY (3.03 Å)