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Cell Rep
. 2024 Jan 3;43(1):113653.
doi: 10.1016/j.celrep.2023.113653. Online ahead of print. Identification of a broad sarbecovirus neutralizing antibody targeting a conserved epitope on the receptor-binding domain
Yanqun Wang 1 , Zhaoyong Zhang 2 , Minnan Yang 3 , Xinyi Xiong 4 , Qihong Yan 2 , Lei Cao 3 , Peilan Wei 5 , Yuting Zhang 2 , Lu Zhang 6 , Kexin Lv 7 , Jiantao Chen 2 , Xuesong Liu 8 , Xiaochu Zhao 9 , Juxue Xiao 2 , Shengnan Zhang 2 , Airu Zhu 2 , Mian Gan 2 , Jingjun Zhang 2 , Ruoxi Cai 2 , Jianfen Zhuo 2 , Yanjun Zhang 2 , Haiyue Rao 2 , Bin Qu 4 , Yuanyuan Zhang 2 , Lei Chen 2 , Jun Dai 6 , Linling Cheng 2 , Qingtao Hu 2 , Yaoqing Chen 7 , Huibin Lv 10 , Ray T Y So 11 , Malik Peiris 12 , Jingxian Zhao 5 , Xiaoqing Liu 13 , Chris Ka Pun Mok 14 , Xiangxi Wang 15 , Jincun Zhao 16
Affiliations
Omicron, as the emerging variant with enhanced vaccine tolerance, has sharply disrupted most therapeutic antibodies. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) belongs to the subgenus Sarbecovirus, members of which share high sequence similarity. Herein, we report one sarbecovirus antibody, 5817, which has broad-spectrum neutralization capacity against SARS-CoV-2 variants of concern (VOCs) and SARS-CoV, as well as related bat and pangolin viruses. 5817 can hardly compete with six classes of receptor-binding-domain-targeted antibodies grouped by structural classifications. No obvious impairment in the potency is detected against SARS-CoV-2 Omicron and subvariants. The cryoelectron microscopy (cryo-EM) structure of neutralizing antibody 5817 in complex with Omicron spike reveals a highly conserved epitope, only existing at the receptor-binding domain (RBD) open state. Prophylactic and therapeutic administration of 5817 potently protects mice from SARS-CoV-2 Beta, Delta, Omicron, and SARS-CoV infection. This study reveals a highly conserved cryptic epitope targeted by a broad sarbecovirus neutralizing antibody, which would be beneficial to meet the potential threat of pre-emergent SARS-CoV-2 VOCs.
Keywords: CP: Immunology; conserved epitope; in vivo; mouse model; neutralizing antibody; receptor binding domain; sarbecovirus.
. 2024 Jan 3;43(1):113653.
doi: 10.1016/j.celrep.2023.113653. Online ahead of print. Identification of a broad sarbecovirus neutralizing antibody targeting a conserved epitope on the receptor-binding domain
Yanqun Wang 1 , Zhaoyong Zhang 2 , Minnan Yang 3 , Xinyi Xiong 4 , Qihong Yan 2 , Lei Cao 3 , Peilan Wei 5 , Yuting Zhang 2 , Lu Zhang 6 , Kexin Lv 7 , Jiantao Chen 2 , Xuesong Liu 8 , Xiaochu Zhao 9 , Juxue Xiao 2 , Shengnan Zhang 2 , Airu Zhu 2 , Mian Gan 2 , Jingjun Zhang 2 , Ruoxi Cai 2 , Jianfen Zhuo 2 , Yanjun Zhang 2 , Haiyue Rao 2 , Bin Qu 4 , Yuanyuan Zhang 2 , Lei Chen 2 , Jun Dai 6 , Linling Cheng 2 , Qingtao Hu 2 , Yaoqing Chen 7 , Huibin Lv 10 , Ray T Y So 11 , Malik Peiris 12 , Jingxian Zhao 5 , Xiaoqing Liu 13 , Chris Ka Pun Mok 14 , Xiangxi Wang 15 , Jincun Zhao 16
Affiliations
- PMID: 38175758
- DOI: 10.1016/j.celrep.2023.113653
Omicron, as the emerging variant with enhanced vaccine tolerance, has sharply disrupted most therapeutic antibodies. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) belongs to the subgenus Sarbecovirus, members of which share high sequence similarity. Herein, we report one sarbecovirus antibody, 5817, which has broad-spectrum neutralization capacity against SARS-CoV-2 variants of concern (VOCs) and SARS-CoV, as well as related bat and pangolin viruses. 5817 can hardly compete with six classes of receptor-binding-domain-targeted antibodies grouped by structural classifications. No obvious impairment in the potency is detected against SARS-CoV-2 Omicron and subvariants. The cryoelectron microscopy (cryo-EM) structure of neutralizing antibody 5817 in complex with Omicron spike reveals a highly conserved epitope, only existing at the receptor-binding domain (RBD) open state. Prophylactic and therapeutic administration of 5817 potently protects mice from SARS-CoV-2 Beta, Delta, Omicron, and SARS-CoV infection. This study reveals a highly conserved cryptic epitope targeted by a broad sarbecovirus neutralizing antibody, which would be beneficial to meet the potential threat of pre-emergent SARS-CoV-2 VOCs.
Keywords: CP: Immunology; conserved epitope; in vivo; mouse model; neutralizing antibody; receptor binding domain; sarbecovirus.