Potent neutralization of SARS-CoV-2 by human antibody heavy-chain variable domains isolated from a large library with a new stable scaffold

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  • Sun, Zehua
    • Other Affiliation: University of Pittsburgh Medical School
  • Chen, Chuan
    • Other Affiliation: University of Pittsburgh Medical School
  • Li, Wei
    • Other Affiliation: University of Pittsburgh Medical School
  • Martinez, David R.
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Drelich, Aleksandra
    • Other Affiliation: Galveston National Laboratory
  • Baek, Du-San
    • Other Affiliation: University of Pittsburgh Medical School
  • Liu, Xianglei
    • Other Affiliation: University of Pittsburgh Medical School
  • Mellors, John W.
    • Other Affiliation: University of Pittsburgh Medical School
  • Tseng, Chien-Te
    • Other Affiliation: Galveston National Laboratory
  • Baric, Ralph S.
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Dimitrov. Dimiter S.
    • Other Affiliation: University of Pittsburgh Medical School
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.
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  • Article
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  • In Copyright
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  • Attribution 3.0 United States
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  • mAbs
Journal volume
  • 12
Journal issue
  • 1
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  • English

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