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TitleBiparatopic antibody BA7208/7125 effectively neutralizes SARS-CoV-2 variants including Omicron BA.1-BA.5.
Journal, issue, pagesCell Discov, Vol. 9, Issue 1, Page 3, Year 2023
Publish dateJan 7, 2023
AuthorsYanqun Wang / An Yan / Deyong Song / Chuangchuang Dong / Muding Rao / Yuanzhu Gao / Ruxi Qi / Xiaomin Ma / Qiaoping Wang / Hongguang Xu / Hong Liu / Jing Han / Maoqin Duan / Shuo Liu / Xiaoping Yu / Mengqi Zong / Jianxia Feng / Jie Jiao / Huimin Zhang / Min Li / Beibei Yu / Yanxia Wang / Fanhao Meng / Xiaodan Ni / Ying Li / Zhenduo Shen / Baiping Sun / Xin Shao / Haifeng Zhao / Yanyan Zhao / Rui Li / Yanan Zhang / Guangying Du / Jun Lu / Chunna You / Hua Jiang / Lu Zhang / Lan Wang / Changlin Dou / Zheng Liu / Jincun Zhao /
PubMed AbstractSARS-CoV-2 Omicron subvariants have demonstrated extensive evasion from monoclonal antibodies (mAbs) developed for clinical use, which raises an urgent need to develop new broad-spectrum mAbs. Here, ...SARS-CoV-2 Omicron subvariants have demonstrated extensive evasion from monoclonal antibodies (mAbs) developed for clinical use, which raises an urgent need to develop new broad-spectrum mAbs. Here, we report the isolation and analysis of two anti-RBD neutralizing antibodies BA7208 and BA7125 from mice engineered to produce human antibodies. While BA7125 showed broadly neutralizing activity against all variants except the Omicron sublineages, BA7208 was potently neutralizing against all tested SARS-CoV-2 variants (including Omicron BA.1-BA.5) except Mu. By combining BA7208 and BA7125 through the knobs-into-holes technology, we generated a biparatopic antibody BA7208/7125 that was able to neutralize all tested circulating SARS-CoV-2 variants. Cryo-electron microscopy structure of these broad-spectrum antibodies in complex with trimeric Delta and Omicron spike indicated that the contact residues are highly conserved and had minimal interactions with mutational residues in RBD of current variants. In addition, we showed that administration of BA7208/7125 via the intraperitoneal, intranasal, or aerosol inhalation route showed potent therapeutic efficacy against Omicron BA.1 and BA.2 in hACE2-transgenic and wild-type mice and, separately, effective prophylaxis. BA7208/7125 thus has the potential to be an effective candidate as an intervention against COVID-19.
External linksCell Discov / PubMed:36609558 / PubMed Central
MethodsEM (single particle)
Resolution2.62 - 3.2 Å
Structure data

33130

7xcz

EMDB-33130, PDB-7xcz:
Cryo-EM structure of SARS-CoV-2 Delta RBD in complex with BA7054 and BA7125 fab (local refinement)
Method: EM (single particle) / Resolution: 3.2 Å

33140

7xda

EMDB-33140, PDB-7xda:
Cryo-EM structure of SARS-CoV-2 Delta RBD in complex with BA7208 and BA7125 fab (local refinement)
Method: EM (single particle) / Resolution: 2.98 Å

33142

7xdb

EMDB-33142, PDB-7xdb:
Cryo-EM structure of SARS-CoV-2 Omicron Spike protein in complex with BA7208 fab
Method: EM (single particle) / Resolution: 2.62 Å

33150

7xdk

EMDB-33150, PDB-7xdk:
Cryo-EM structure of SARS-CoV-2 Delta Spike protein in complex with BA7054 and BA7125 fab
Method: EM (single particle) / Resolution: 3.2 Å

33151

7xdl

EMDB-33151, PDB-7xdl:
Cryo-EM structure of SARS-CoV-2 Delta Spike protein in complex with BA7208 and BA7125 fab
Method: EM (single particle) / Resolution: 3.08 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

Source
  • severe acute respiratory syndrome coronavirus 2
  • homo sapiens (human)
KeywordsVIRAL PROTEIN / SARS-CoV-2 Delta / spike / fab / Cryo-EM

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