tetano
Editor, Senior Moderator
MAbs
. 2020 Jan 1;12(1):1778435.
doi: 10.1080/19420862.2020.1778435.
Potent Neutralization of SARS-CoV-2 by Human Antibody Heavy-Chain Variable Domains Isolated From a Large Library With a New Stable Scaffold
Zehua Sun[SUP] 1 [/SUP], Chuan Chen[SUP] 1 [/SUP], Wei Li[SUP] 1 [/SUP], David R Martinez[SUP] 2 [/SUP], Aleksandra Drelich[SUP] 3 [/SUP], Du-San Baek[SUP] 1 [/SUP], Xianglei Liu[SUP] 1 [/SUP], John W Mellors[SUP] 1 4 [/SUP], Chien-Te Tseng[SUP] 3 [/SUP], Ralph S Baric[SUP] 2 [/SUP], Dimiter S Dimitrov[SUP] 1 4 [/SUP]
Affiliations
Abstract
Effective therapies are urgently needed for COVID-19. Here we describe the identification of a new stable human immunoglobulin G1 heavy-chain variable (VH) domain scaffold that was used for the construction of a large library, lCAT6, of engineered human VHs. This library was panned against the receptor-binding domain (RBD) of the SARS-CoV-2 spike (S) glycoprotein. Two VH domains (VH ab6 and VH m397) were selected and fused to Fc for increased half-life in circulation. The VH-Fc ab6 and m397 specifically neutralized SARS-CoV-2 with high potencies (50% neutralization at 0.35 ?g/ml and 1.5 ?g/ml, respectively) as measured by two independent replication-competent virus neutralization assays. Ab6 and m397 competed with ACE2 for binding to RBD, suggesting a competitive mechanism of virus neutralization. These VH domains may have potential applications for prophylaxis and therapy of COVID-19 alone or in combination, as well as for diagnosis and as tools for research.
Keywords: SARS-CoV-2; Therapeutic antibodies; coronaviruses.
. 2020 Jan 1;12(1):1778435.
doi: 10.1080/19420862.2020.1778435.
Potent Neutralization of SARS-CoV-2 by Human Antibody Heavy-Chain Variable Domains Isolated From a Large Library With a New Stable Scaffold
Zehua Sun[SUP] 1 [/SUP], Chuan Chen[SUP] 1 [/SUP], Wei Li[SUP] 1 [/SUP], David R Martinez[SUP] 2 [/SUP], Aleksandra Drelich[SUP] 3 [/SUP], Du-San Baek[SUP] 1 [/SUP], Xianglei Liu[SUP] 1 [/SUP], John W Mellors[SUP] 1 4 [/SUP], Chien-Te Tseng[SUP] 3 [/SUP], Ralph S Baric[SUP] 2 [/SUP], Dimiter S Dimitrov[SUP] 1 4 [/SUP]
Affiliations
- PMID: 32544372
- DOI: 10.1080/19420862.2020.1778435
Abstract
Effective therapies are urgently needed for COVID-19. Here we describe the identification of a new stable human immunoglobulin G1 heavy-chain variable (VH) domain scaffold that was used for the construction of a large library, lCAT6, of engineered human VHs. This library was panned against the receptor-binding domain (RBD) of the SARS-CoV-2 spike (S) glycoprotein. Two VH domains (VH ab6 and VH m397) were selected and fused to Fc for increased half-life in circulation. The VH-Fc ab6 and m397 specifically neutralized SARS-CoV-2 with high potencies (50% neutralization at 0.35 ?g/ml and 1.5 ?g/ml, respectively) as measured by two independent replication-competent virus neutralization assays. Ab6 and m397 competed with ACE2 for binding to RBD, suggesting a competitive mechanism of virus neutralization. These VH domains may have potential applications for prophylaxis and therapy of COVID-19 alone or in combination, as well as for diagnosis and as tools for research.
Keywords: SARS-CoV-2; Therapeutic antibodies; coronaviruses.