tetano
Editor, Senior Moderator
Emerg Microbes Infect
. 2024 Oct 29:2406300.
doi: 10.1080/22221751.2024.2406300. Online ahead of print. Structural insight into broadening SARS-CoV-2 neutralization by an antibody cocktail harboring both NTD and RBD potent antibodies
Wenling Jiang[SUP] 1 2 [/SUP], Yanan Jiang[SUP] 1 2 [/SUP], Hui Sun[SUP] 1 2 [/SUP], Tingting Deng[SUP] 1 2 [/SUP], Kunyu Yu[SUP] 1 2 [/SUP], Qianjiao Fang[SUP] 1 2 [/SUP], Huimin Ge[SUP] 1 2 [/SUP], Miaoling Lan[SUP] 1 2 [/SUP], Yanling Lin[SUP] 1 2 [/SUP], Zhongyue Fang[SUP] 1 2 [/SUP], Yali Zhang[SUP] 1 2 [/SUP], Lizhi Zhou[SUP] 1 2 [/SUP], Tingting Li[SUP] 1 2 [/SUP], Hai Yu[SUP] 1 2 [/SUP], Qingbing Zheng[SUP] 1 2 [/SUP], Shaowei Li[SUP] 1 2 [/SUP], Ningshao Xia[SUP] 1 2 [/SUP], Ying Gu[SUP] 1 2 [/SUP]
Affiliations
The continual emergence of highly pathogenic novel coronaviruses and their variants has underscored the importance of neutralizing monoclonal antibodies (mAbs) as a pivotal therapeutic approach. In the present study, we report the specific neutralizing antibodies 13H7 and 9G11, which target the N-terminal domain (NTD) and receptor-binding domain (RBD) of the SARS-CoV-2, respectively. The comparative analysis observed that 13H7 not only neutralizes early variants of concern (VOCs) but also exhibits neutralizing activity against the Omicron sublineage, including BA.4, BA.5, BQ.1, and BQ.1.1. 9G11, as an RBD antibody, also demonstrated remarkable neutralizing efficacy. A cocktail antibody combining 13H7 and 9G11 with the previously reported 3E2 broaden the neutralization spectrum against new variants of the SARS-CoV-2. We elucidated the cryo-EM structure of the complex, clarifying the mechanism of action of the cocktail antibody combination. Additionally, we also emphasized the molecular mechanism between 13H7 and SARS-CoV-2 NTD, revealing the impact of Y144 and H146 residue deletions and mutations on the neutralizing efficacy of 13H7. Taken together, our findings not only offer novel insights into the combination therapy of NTD and RBD neutralizing mAbs but also lay a theoretical foundation for the development of vaccines targeting NTD antibodies, thus providing valuable understanding of alleviating the emergence of SARS-CoV-2 variants.
Keywords: Antibody Cocktails; NTD and RBD; Neutralizing Monoclonal Antibodies; Omicron Variants; SARS-CoV-2.
. 2024 Oct 29:2406300.
doi: 10.1080/22221751.2024.2406300. Online ahead of print. Structural insight into broadening SARS-CoV-2 neutralization by an antibody cocktail harboring both NTD and RBD potent antibodies
Wenling Jiang[SUP] 1 2 [/SUP], Yanan Jiang[SUP] 1 2 [/SUP], Hui Sun[SUP] 1 2 [/SUP], Tingting Deng[SUP] 1 2 [/SUP], Kunyu Yu[SUP] 1 2 [/SUP], Qianjiao Fang[SUP] 1 2 [/SUP], Huimin Ge[SUP] 1 2 [/SUP], Miaoling Lan[SUP] 1 2 [/SUP], Yanling Lin[SUP] 1 2 [/SUP], Zhongyue Fang[SUP] 1 2 [/SUP], Yali Zhang[SUP] 1 2 [/SUP], Lizhi Zhou[SUP] 1 2 [/SUP], Tingting Li[SUP] 1 2 [/SUP], Hai Yu[SUP] 1 2 [/SUP], Qingbing Zheng[SUP] 1 2 [/SUP], Shaowei Li[SUP] 1 2 [/SUP], Ningshao Xia[SUP] 1 2 [/SUP], Ying Gu[SUP] 1 2 [/SUP]
Affiliations
- PMID: 39470577
- DOI: 10.1080/22221751.2024.2406300
The continual emergence of highly pathogenic novel coronaviruses and their variants has underscored the importance of neutralizing monoclonal antibodies (mAbs) as a pivotal therapeutic approach. In the present study, we report the specific neutralizing antibodies 13H7 and 9G11, which target the N-terminal domain (NTD) and receptor-binding domain (RBD) of the SARS-CoV-2, respectively. The comparative analysis observed that 13H7 not only neutralizes early variants of concern (VOCs) but also exhibits neutralizing activity against the Omicron sublineage, including BA.4, BA.5, BQ.1, and BQ.1.1. 9G11, as an RBD antibody, also demonstrated remarkable neutralizing efficacy. A cocktail antibody combining 13H7 and 9G11 with the previously reported 3E2 broaden the neutralization spectrum against new variants of the SARS-CoV-2. We elucidated the cryo-EM structure of the complex, clarifying the mechanism of action of the cocktail antibody combination. Additionally, we also emphasized the molecular mechanism between 13H7 and SARS-CoV-2 NTD, revealing the impact of Y144 and H146 residue deletions and mutations on the neutralizing efficacy of 13H7. Taken together, our findings not only offer novel insights into the combination therapy of NTD and RBD neutralizing mAbs but also lay a theoretical foundation for the development of vaccines targeting NTD antibodies, thus providing valuable understanding of alleviating the emergence of SARS-CoV-2 variants.
Keywords: Antibody Cocktails; NTD and RBD; Neutralizing Monoclonal Antibodies; Omicron Variants; SARS-CoV-2.