8XRQ

SARS-CoV-2 BA.1 spike RBD in complex bound with VacBB-639

Summary for 8XRQ

• Entry DOI: 10.2210/pdb8xrq/pdb
• EMDB information: 38610
• Descriptor: Spike protein S1, Heavy chain of VacBB 639 Fab, Light chain of VacBB 639 Fab (3 entities in total)
• Functional Keywords: antibody, viral protein-immune system complex, protein binding
• Biological source: Severe acute respiratory syndrome coronavirus 2; More
• Total number of polymer chains: 3
• Total formula weight: 50406.60

Authors

Liu, C.C.,Ju, B.,Zhang, Z. (deposition date: 2024-01-08, release date: 2024-12-18, Last modification date: 2025-03-26)

Primary citation

Wang, M.,Liu, C.,Fan, Q.,Sun, Y.,Tang, S.,Guo, H.,Zhou, B.,Wang, H.,Ge, X.,Zhang, Z.,Ju, B.
Rapid clonal expansion and somatic hypermutation contribute to the fate of SARS-CoV-2 broadly neutralizing antibodies.
J Immunol., 214:278-289, 2025

PubMed Abstract: Several vaccines and immunization strategies, including inactivated vaccines, have proven effective in eliciting antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), providing an opportunity to characterize the antibody response. In this study, we investigated the monoclonal antibody responses elicited by wild-type SARS-CoV-2 inactivated vaccination compared to those elicited by natural infection and mRNA vaccination. The analysis showed that antibodies encoded by biased germline genes were shared between SARS-CoV-2 vaccinated and naturally infected individuals. Among the 35 shared clonotypes identified, besides the well-known IGHV3-53 and IGHV1-58, we identified a class of IGHV4-59 antibodies characterized by rapid response and neutralizing activity, elicited by 3 doses of inactivated vaccine. Members of this lineage exhibited similar sensitivity against wild-type SARS-CoV-2, whereas different neutralizing activities against SARS-CoV-2 variants, especially against various Omicron subvariants, BA.1, BA.2, BA.2.12.1, BA.4/5, and BA.2.75. Structural analysis of BA.1 spike complexed with VacBB-639 revealed that the IGHV4-59-lineage antibodies belonged to the Class 2/3 group. Using sequence alignment, site-mutation assays, and functional verification, we identified two substitutions, N60K in HFR3 and S56G in HCDR2, contributing to opposite neutralization changes of IGHV4-59-lineage antibodies against these Omicron subvariants. These results demonstrate the importance of somatic hypermutation in the evolution of prototypical antigen-elicited antibodies in terms of their neutralization breadth and potency against SARS-CoV-2 Omicron variants.

PubMed: 40073246
DOI: 10.1093/jimmun/vkae056

Experimental method

ELECTRON MICROSCOPY (4.19 Å)