8GS9

SARS-CoV-2 BA.2 spike RBD in complex bound with VacBB-551

Summary for 8GS9

• Entry DOI: 10.2210/pdb8gs9/pdb
• EMDB information: 34226
• Descriptor: Spike glycoprotein, Heavy chain of VacBB-551, Light chain of VacBB-551 (3 entities in total)
• Functional Keywords: antibody, viral protein-immune system complex, viral protein/immune system
• Biological source: Severe acute respiratory syndrome coronavirus 2; More
• Total number of polymer chains: 3
• Total formula weight: 44187.40

Authors

Liu, C.C.,Ju, B.,Shen, S.L.,Zhang, Z. (deposition date: 2022-09-05, release date: 2023-05-03, Last modification date: 2024-11-06)

Primary citation

Ju, B.,Fan, Q.,Liu, C.,Shen, S.,Wang, M.,Guo, H.,Zhou, B.,Ge, X.,Zhang, Z.
Omicron BQ.1.1 and XBB.1 unprecedentedly escape broadly neutralizing antibodies elicited by prototype vaccination.
Cell Rep, 42:112532-112532, 2023

PubMed Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariants have seriously attacked the antibody barrier established by natural infection and/or vaccination, especially the recently emerged BQ.1.1 and XBB.1. However, crucial mechanisms underlying the virus escape and the broad neutralization remain elusive. Here, we present a panoramic analysis of broadly neutralizing activity and binding epitopes of 75 monoclonal antibodies isolated from prototype inactivated vaccinees. Nearly all neutralizing antibodies (nAbs) partly or totally lose their neutralization against BQ.1.1 and XBB.1. We report a broad nAb, VacBB-551, that effectively neutralizes all tested subvariants including BA.2.75, BQ.1.1, and XBB.1. We determine the cryoelectron microscopy (cryo-EM) structure of VacBB-551 complexed with the BA.2 spike and perform detailed functional verification to reveal the molecular basis of N460K and F486V/S mutations mediating the partial escape of BA.2.75, BQ.1.1, and XBB.1 from the neutralization of VacBB-551. Overall, BQ.1.1 and XBB.1 raised the alarm over SARS-CoV-2 evolution with unprecedented antibody evasion from broad nAbs elicited by prototype vaccination.

PubMed: 37219999
DOI: 10.1016/j.celrep.2023.112532

Experimental method

ELECTRON MICROSCOPY (2.66 Å)