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TitleA novel bispecific antibody targeting two overlapping epitopes in RBD improves neutralizing potency and breadth against SARS-CoV-2.
Journal, issue, pagesEmerg Microbes Infect, Vol. 13, Issue 1, Page 2373307, Year 2024
Publish dateJul 12, 2024
AuthorsHancong Sun / Lingyun Xia / Jianhua Li / Yuanyuan Zhang / Guanying Zhang / Ping Huang / Xingxing Wang / Yue Cui / Ting Fang / Pengfei Fan / Qiang Zhou / Xiangyang Chi / Changming Yu /
PubMed AbstractSARS-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 ...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.
External linksEmerg Microbes Infect / PubMed:38953857 / PubMed Central
MethodsEM (single particle)
Resolution2.7 - 3.4 Å
Structure data

EMDB-39645, PDB-8yww:
The structure of HKU1-B S protein with bsAb1
Method: EM (single particle) / Resolution: 2.7 Å

EMDB-39646, PDB-8ywx:
the complex structure of the H4B6 Fab with the RBD of Omicron BA.5 S protein
Method: EM (single particle) / Resolution: 3.4 Å

Source
  • severe acute respiratory syndrome coronavirus 2
  • homo sapiens (human)
KeywordsVIRAL PROTEIN/IMMUNE SYSTEM / SARS-CoV-2 / Antibody / VIRAL PROTEIN-IMMUNE SYSTEM complex

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