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Title | Mechanism of a rabbit monoclonal antibody broadly neutralizing SARS-CoV-2 variants. |
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Journal, issue, pages | Commun Biol, Vol. 6, Issue 1, Page 364, Year 2023 |
Publish date | Apr 3, 2023 |
Authors | Hangtian Guo / Yixuan Yang / Tiantian Zhao / Yuchi Lu / Yan Gao / Tinghan Li / Hang Xiao / Xiaoyu Chu / Le Zheng / Wanting Li / Hao Cheng / Haibin Huang / Yang Liu / Yang Lou / Henry C Nguyen / Chao Wu / Yuxin Chen / Haitao Yang / Xiaoyun Ji / |
PubMed Abstract | Due to the continuous evolution of SARS-CoV-2, the Omicron variant has emerged and exhibits severe immune evasion. The high number of mutations at key antigenic sites on the spike protein has made a ...Due to the continuous evolution of SARS-CoV-2, the Omicron variant has emerged and exhibits severe immune evasion. The high number of mutations at key antigenic sites on the spike protein has made a large number of existing antibodies and vaccines ineffective against this variant. Therefore, it is urgent to develop efficient broad-spectrum neutralizing therapeutic drugs. Here we characterize a rabbit monoclonal antibody (RmAb) 1H1 with broad-spectrum neutralizing potency against Omicron sublineages including BA.1, BA.1.1, BA.2, BA.2.12.1, BA.2.75, BA.3 and BA.4/5. Cryo-electron microscopy (cryo-EM) structure determination of the BA.1 spike-1H1 Fab complexes shows that 1H1 targets a highly conserved region of RBD and avoids most of the circulating Omicron mutations, explaining its broad-spectrum neutralization potency. Our findings indicate 1H1 as a promising RmAb model for designing broad-spectrum neutralizing antibodies and shed light on the development of therapeutic agents as well as effective vaccines against newly emerging variants in the future. |
External links | Commun Biol / PubMed:37012333 / PubMed Central |
Methods | EM (single particle) |
Resolution | 3.41 - 3.7 Å |
Structure data | EMDB-34406, PDB-8gzz: EMDB-34407, PDB-8h00: EMDB-34408, PDB-8h01: EMDB-35328: cryo-EM density map of SARS-CoV-2 Omicron BA.1 spike in complex with RmAb 1H1 IgG |
Chemicals | ChemComp-NAG: |
Source |
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Keywords | VIRAL PROTEIN/IMMUNE SYSTEM / VIRAL PROTEIN-IMMUNE SYSTEM COMPLEX |