An engineered bispecific human monoclonal antibody against SARS-CoV-2

Li, Zhaohui; Li, Shihua; Zhang, Gen; Peng, Wanyue; Chang, Zhen; Zhang, Xue; Fan, Zheng; Chai, Yan; Wang, Feiran; Zhao, Xin; Li, Dedong; Zhang, Rong; He, Zhanlong; Zou, Weiwei; Xu, Ke; Lei, Wenwen; Li, Peipei; Hao, Junfeng; Zhang, Jingjing; Sun, Litao; Wu, Guizhen; Tan, Shuguang; Gao, Lidong; Gao, Feng; Wu, Yan

doi:10.1038/s41590-022-01138-w

Cited by 43 publications

(26 citation statements)

References 54 publications

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“…Importantly, however, some mutation sites in the RBD-such as K417, E484, and N501-are well known for causing immune escapes (Harvey et al, 2021;Li et al, 2021Li et al, , 2022Zhou et al, 2021), although previously rare mutations represent new sites that may lead to further immune escapes. Such mutations identified in the RBD raise questions regarding the efficacy of the vaccines and antibodies currently in use against Omicron.…”

Section: Introductionmentioning

confidence: 99%

Atlas of currently available human neutralizing antibodies against SARS-CoV-2 and escape by Omicron sub-variants BA.1/BA.1.1/BA.2/BA.3

Huang

Zheng

et al. 2022

Immunity

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Section: Introductionmentioning

confidence: 99%

Atlas of currently available human neutralizing antibodies against SARS-CoV-2 and escape by Omicron sub-variants BA.1/BA.1.1/BA.2/BA.3

Huang

Zheng

et al. 2022

Immunity

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“…Bispecific or multiple specific antibodies targeting different regions of the spike protein are a favorable strategy by which to treat COVID-19 caused by the ongoing emergence of new SARS-CoV-2 VOCs ( 49 , 50 ). Except for the increased threshold to produce neutralizing escape mutants, bispecific antibodies have practical and cost advantages over the MAb cocktail strategy since the complicated formulation of MAb cocktails routinely increases manufacturing costs and volumes.…”

Section: Discussionmentioning

confidence: 99%

A Bispecific Antibody Targeting RBD and S2 Potently Neutralizes SARS-CoV-2 Omicron and Other Variants of Concern

Yuan

Chen

Zhu

et al. 2022

J Virol

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“…Bispecific or multiple specific antibodies targeting different regions of the spike protein are a favorable strategy to treat COVID-19 caused by the ongoing emergence of new SARS-CoV-2 VOCs[48, 49]. Except for the increased threshold to produce neutralizing escape mutants, bispecific antibodies have practical and cost advantages over the mAb cocktail strategy since the complicated formulation of mAb cocktails routinely increases manufacturing costs and volumes.…”

Section: Discussionmentioning

confidence: 99%

A Bispecific Antibody Targeting RBD and S2 Potently Neutralizes SARS-CoV-2 Omicron and Other Variants of Concern

Yuan

Chen

Zhu

et al. 2022

Preprint

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Emerging severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) variants, especially the Omicron variant, have impaired the efficacy of existing vaccines and most therapeutic antibodies, highlighting the need for additional antibody-based tools that can efficiently neutralize emerging SARS-CoV-2 variants. The use of a “single” agent to simultaneously target multiple distinct epitopes on the spike is desirable to overcome the neutralizing escape of SARS-CoV-2 variants. Herein, we generated a human-derived IgG-like bispecific antibody (bsAb), Bi-Nab35B5-47D10, which successfully retained the specificity and simultaneously bound to the two distinct epitopes on RBD and S2. Bi-Nab35B5-47D10 showed improved spike binding breadth among wild-type (WT) SARS-CoV-2, variants of concern (VOCs) and variants being monitored (VBMs) compared with its parental mAbs. Furthermore, pseudotyped virus neutralization demonstrated that Bi-Nab35B5-47D10 can efficiently neutralize VBMs including Alpha (B.1.1.7), Beta (B.1.351) and Kappa (B.1.617.1) and VOCs including Delta (B.1.617.2), Omicron BA.1 and Omicron BA.2. Crucially, Bi-Nab35B5-47D10 substantially improved neutralizing activity against Omicron BA.1 (IC50= 27.3 ng/mL) and Omicron BA.2 (IC50= 121.1 ng/mL) compared with their parental mAbs. Therefore, Bi-Nab35B5-47D10 represents a potential effective countermeasure against SARS-CoV-2 Omicron and other variants of concern.ImportanceThe new highly contagious SARS-CoV-2 Omicron variant caused substantial breakthrough infections and has become the dominant strain in countries across the world. Omicron variants usually bear high mutations in the spike protein and exhibit considerable escape of most potent neutralization monoclonal antibodies and reduced efficacy of current COVID-19 vaccines. The development of neutralizing antibodies with potent efficacy against the Omicron variant is still an urgent priority. Here, we generated a bsAb, Bi-Nab35B5-47D10, that simultaneously targets SARS-CoV-2 RBD and S2 and improved neutralizing potency and breadth against SARS-CoV-2 WT and the tested variants compared with their parental antibodies. Notably, Bi-Nab35B5-47D10 has more potent neutralizing activity against the VOC Omicron pseudotyped virus. Therefore, Bi-Nab35B5-47D10 is a feasible and potentially effective strategy to treat and prevent COVID-19.

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An engineered bispecific human monoclonal antibody against SARS-CoV-2

Cited by 43 publications

References 54 publications

Atlas of currently available human neutralizing antibodies against SARS-CoV-2 and escape by Omicron sub-variants BA.1/BA.1.1/BA.2/BA.3

Atlas of currently available human neutralizing antibodies against SARS-CoV-2 and escape by Omicron sub-variants BA.1/BA.1.1/BA.2/BA.3

A Bispecific Antibody Targeting RBD and S2 Potently Neutralizes SARS-CoV-2 Omicron and Other Variants of Concern

A Bispecific Antibody Targeting RBD and S2 Potently Neutralizes SARS-CoV-2 Omicron and Other Variants of Concern

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