8YWX

the complex structure of the H4B6 Fab with the RBD of Omicron BA.5 S protein

Summary for 8YWX

• Entry DOI: 10.2210/pdb8ywx/pdb
• EMDB information: 39646
• Descriptor: H4B6 Fab's heavy chain, H4B6 Fab's light chain, Spike protein S2' (3 entities in total)
• Functional Keywords: antibody, viral protein/immune system, viral protein-immune system complex
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 3
• Total formula weight: 223945.10

Authors

Xia, L.Y.,Zhang, Y.Y.,Zhou, Q. (deposition date: 2024-04-01, release date: 2024-07-31, Last modification date: 2024-11-13)

Primary citation

Sun, H.,Xia, L.,Li, J.,Zhang, Y.,Zhang, G.,Huang, P.,Wang, X.,Cui, Y.,Fang, T.,Fan, P.,Zhou, Q.,Chi, X.,Yu, C.
A novel bispecific antibody targeting two overlapping epitopes in RBD improves neutralizing potency and breadth against SARS-CoV-2.
Emerg Microbes Infect, 13:2373307-2373307, 2024

PubMed Abstract: SARS-CoV-2 has been evolving into a large number of variants, including the highly pathogenic Delta variant, and the currently prevalent Omicron subvariants with extensive evasion capability, which raises an urgent need to develop new broad-spectrum neutralizing antibodies. Herein, we engineer two IgG-(scFv) form bispecific antibodies with overlapping epitopes (bsAb1) or non-overlapping epitopes (bsAb2). Both bsAbs are significantly superior to the parental monoclonal antibodies in terms of their antigen-binding and virus-neutralizing activities against all tested circulating SARS-CoV-2 variants including currently dominant JN.1. The bsAb1 can efficiently neutralize all variants insensitive to parental monoclonal antibodies or the cocktail with IC lower than 20 ng/mL, even slightly better than bsAb2. Furthermore, the cryo-EM structures of bsAb1 in complex with the Omicron spike protein revealed that bsAb1 with overlapping epitopes effectively locked the S protein, which accounts for its conserved neutralization against Omicron variants. The bispecific antibody strategy engineered from overlapping epitopes provides a novel solution for dealing with viral immune evasion.

PubMed: 38953857
DOI: 10.1080/22221751.2024.2373307

Experimental method

ELECTRON MICROSCOPY (3.4 Å)