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, Chuan Chen, Wei Li, David R. Martinez, Aleksandra Drelich, Du San Baek, Xianglei Liu, John W. Mellors, Chien Te Tseng, Ralph S. Baric, Dimiter S. Dimitrov

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number1778435
JournalmAbs
Volume12
Issue number1
DOIs
StatePublished - Jan 1 2020

Keywords

  • SARS-CoV-2
  • Therapeutic antibodies
  • coronaviruses

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'Potent neutralization of SARS-CoV-2 by human antibody heavy-chain variable domains isolated from a large library with a new stable scaffold'. Together they form a unique fingerprint.

  • Cite this

    Sun, Z., Chen, C., Li, W., Martinez, D. R., Drelich, A., Baek, D. S., Liu, X., Mellors, J. W., Tseng, C. T., Baric, R. S., & Dimitrov, D. S. (2020). Potent neutralization of SARS-CoV-2 by human antibody heavy-chain variable domains isolated from a large library with a new stable scaffold. mAbs, 12(1), [1778435]. https://doi.org/10.1080/19420862.2020.1778435