Nature Communications (Jun 2024)

A bispecific antibody exhibits broad neutralization against SARS-CoV-2 Omicron variants XBB.1.16, BQ.1.1 and sarbecoviruses

  • Yingdan Wang,
  • Aihua Hao,
  • Ping Ji,
  • Yunping Ma,
  • Zhaoyong Zhang,
  • Jiali Chen,
  • Qiyu Mao,
  • Xinyi Xiong,
  • Palizhati Rehati,
  • Yajie Wang,
  • Yanqun Wang,
  • Yumei Wen,
  • Lu Lu,
  • Zhenguo Chen,
  • Jincun Zhao,
  • Fan Wu,
  • Jinghe Huang,
  • Lei Sun

DOI
https://doi.org/10.1038/s41467-024-49096-1
Journal volume & issue
Vol. 15, no. 1
pp. 1 – 13

Abstract

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Abstract The Omicron subvariants BQ.1.1, XBB.1.5, and XBB.1.16 of SARS-CoV-2 are known for their adeptness at evading immune responses. Here, we isolate a neutralizing antibody, 7F3, with the capacity to neutralize all tested SARS-CoV-2 variants, including BQ.1.1, XBB.1.5, and XBB.1.16. 7F3 targets the receptor-binding motif (RBM) region and exhibits broad binding to a panel of 37 RBD mutant proteins. We develop the IgG-like bispecific antibody G7-Fc using 7F3 and the cross-neutralizing antibody GW01. G7-Fc demonstrates robust neutralizing activity against all 28 tested SARS-CoV-2 variants and sarbecoviruses, providing potent prophylaxis and therapeutic efficacy against XBB.1 infection in both K18-ACE and BALB/c female mice. Cryo-EM structure analysis of the G7-Fc in complex with the Omicron XBB spike (S) trimer reveals a trimer-dimer conformation, with G7-Fc synergistically targeting two distinct RBD epitopes and blocking ACE2 binding. Comparative analysis of 7F3 and LY-CoV1404 epitopes highlights a distinct and highly conserved epitope in the RBM region bound by 7F3, facilitating neutralization of the immune-evasive Omicron variant XBB.1.16. G7-Fc holds promise as a potential prophylactic countermeasure against SARS-CoV-2, particularly against circulating and emerging variants.