@article{5a44be500301486ba9a329e4a6e2b6d6,
title = "Potent neutralization of SARS-CoV-2 by human antibody heavy-chain variable domains isolated from a large library with a new stable scaffold",
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 µg/ml and 1.5 µg/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",
author = "Zehua Sun and Chuan Chen and Wei Li and Martinez, {David R.} and Aleksandra Drelich and Baek, {Du San} and Xianglei Liu and Mellors, {John W.} and Tseng, {Chien Te} and Baric, {Ralph S.} and Dimitrov, {Dimiter S.}",
note = "Funding Information: This work was supported by the University of Pittsburgh Medical Center. [University of Pittsburgh Medical Center.]; NIH [AI132178 and AI108197]. We would like to thank the members of the Center for Antibody Therapeutics Doncho Zhelev, Cynthia Adams and Xioajie Chu for their help with some of the experiments and helpful discussions. We also thank Rui Gong from the Institute of Virology in Wuhan and Rachel Fong from Integral Molecular for helpful suggestions. This work was supported by the University of Pittsburgh Medical Center. David R. Martinez is funded by an NIH NIAID T32 AI007151 and a Burroughs Welcome Fund Postdoctoral Enrichment Program Award. RSB is supported by grants from the NIH AI132178 and AI108197. Some monoclonal antibodies were generated by the University of North Carolina Protein Expression and Purification core facility, which is funded by NIH grant P30CA016086. Funding Information: We would like to thank the members of the Center for Antibody Therapeutics Doncho Zhelev, Cynthia Adams and Xioajie Chu for their help with some of the experiments and helpful discussions. We also thank Rui Gong from the Institute of Virology in Wuhan and Rachel Fong from Integral Molecular for helpful suggestions. This work was supported by the University of Pittsburgh Medical Center. David R. Martinez is funded by an NIH NIAID T32 AI007151 and a Burroughs Welcome Fund Postdoctoral Enrichment Program Award. RSB is supported by grants from the NIH AI132178 and AI108197. Some monoclonal antibodies were generated by the University of North Carolina Protein Expression and Purification core facility, which is funded by NIH grant P30CA016086. Publisher Copyright: {\textcopyright} 2020, {\textcopyright} 2020 University of Pittsburgh. Published with license by Taylor & Francis Group, LLC.",
year = "2020",
month = jan,
day = "1",
doi = "10.1080/19420862.2020.1778435",
language = "English (US)",
volume = "12",
journal = "mAbs",
issn = "1942-0862",
publisher = "Landes Bioscience",
number = "1",
}