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Nat Commun
. 2024 Jun 15;15(1):5127.
doi: 10.1038/s41467-024-49096-1. A bispecific antibody exhibits broad neutralization against SARS-CoV-2 Omicron variants XBB.1.16, BQ.1.1 and sarbecoviruses
Yingdan Wang # 1 2 , Aihua Hao # 1 , Ping Ji # 1 , Yunping Ma # 1 3 , Zhaoyong Zhang # 4 , Jiali Chen 1 , Qiyu Mao 1 , Xinyi Xiong 4 , Palizhati Rehati 1 , Yajie Wang 1 , Yanqun Wang 4 , Yumei Wen 1 , Lu Lu 1 , Zhenguo Chen 1 , Jincun Zhao 5 6 , Fan Wu 7 , Jinghe Huang 8 9 , Lei Sun 10
Affiliations
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.
. 2024 Jun 15;15(1):5127.
doi: 10.1038/s41467-024-49096-1. A bispecific antibody exhibits broad neutralization against SARS-CoV-2 Omicron variants XBB.1.16, BQ.1.1 and sarbecoviruses
Yingdan Wang # 1 2 , Aihua Hao # 1 , Ping Ji # 1 , Yunping Ma # 1 3 , Zhaoyong Zhang # 4 , Jiali Chen 1 , Qiyu Mao 1 , Xinyi Xiong 4 , Palizhati Rehati 1 , Yajie Wang 1 , Yanqun Wang 4 , Yumei Wen 1 , Lu Lu 1 , Zhenguo Chen 1 , Jincun Zhao 5 6 , Fan Wu 7 , Jinghe Huang 8 9 , Lei Sun 10
Affiliations
- PMID: 38879565
- PMCID: PMC11180174
- DOI: 10.1038/s41467-024-49096-1
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.