Ultrapotent antibodies against diverse and highly transmissible SARS-CoV-2 variants

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  • Wang, L.
    • Other Affiliation: National Institutes of Health
  • Zhou, T.
    • Other Affiliation: National Institutes of Health
  • Zhang, Y.
    • Other Affiliation: National Institutes of Health
  • Yang, E.S.
    • Other Affiliation: National Institutes of Health
  • Schramm, C.A.
    • Other Affiliation: National Institutes of Health
  • Shi, W.
    • Other Affiliation: National Institutes of Health
  • Pegu, A.
    • Other Affiliation: National Institutes of Health
  • Oloniniyi, O.K.
    • Other Affiliation: National Institutes of Health
  • Henry, A.R.
    • Other Affiliation: National Institutes of Health
  • Darko, S.
    • Other Affiliation: National Institutes of Health
  • Narpala, S.R.
    • Other Affiliation: National Institutes of Health
  • Hatcher, C.
    • Other Affiliation: National Institutes of Health
  • Martinez, D.R.
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Tsybovsky, Y.
    • Other Affiliation: Frederic National Laboratory for Cancer Research
  • Phung, E.
    • Other Affiliation: National Institutes of Health
  • Abiona, O.M.
    • Other Affiliation: National Institutes of Health
  • Antia, A.
    • Other Affiliation: National Institutes of Health
  • Cale, E.M.
    • Other Affiliation: National Institutes of Health
  • Chang, L.A.
    • Other Affiliation: National Institutes of Health
  • Choe, M.
    • Other Affiliation: National Institutes of Health
  • Corbett, K.S.
    • Other Affiliation: National Institutes of Health
  • Davis, R.L.
    • Other Affiliation: National Institutes of Health
  • DiPiazza, A.T.
    • Other Affiliation: National Institutes of Health
  • Gordon, I.J.
    • Other Affiliation: National Institutes of Health
  • Hait, S.H.
    • Other Affiliation: National Institutes of Health
  • Hermanus, T.
    • Other Affiliation: University of the Witwatersrand
  • Kgagudi, P.
    • Other Affiliation: University of the Witwatersrand
  • Laboune, F.
    • Other Affiliation: National Institutes of Health
  • Leung, K.
    • Other Affiliation: National Institutes of Health
  • Liu, T.
    • Other Affiliation: National Institutes of Health
  • Mason, R.D.
    • Other Affiliation: National Institutes of Health
  • Nazzari, A.F.
    • Other Affiliation: National Institutes of Health
  • Novik, L.
    • Other Affiliation: National Institutes of Health
  • O'Connell, S.
    • Other Affiliation: National Institutes of Health
  • O'Dell, S.
    • Other Affiliation: National Institutes of Health
  • Olia, A.S.
    • Other Affiliation: National Institutes of Health
  • Schmidt, S.D.
    • Other Affiliation: National Institutes of Health
  • Stephens, T.
    • Other Affiliation: Frederic National Laboratory for Cancer Research
  • Stringham, C.D.
    • Other Affiliation: National Institutes of Health
  • Talana, C.A.
    • Other Affiliation: National Institutes of Health
  • Teng, I.-T.
    • Other Affiliation: National Institutes of Health
  • Wagner, D.A.
    • Other Affiliation: National Institutes of Health
  • Widge, A.T.
    • Other Affiliation: National Institutes of Health
  • Zhang, B.
    • Other Affiliation: National Institutes of Health
  • Roederer, M.
    • Other Affiliation: National Institutes of Health
  • Ledgerwood, J.E.
    • Other Affiliation: National Institutes of Health
  • Ruckwardt, T.J.
    • Other Affiliation: National Institutes of Health
  • Gaudinski, M.R.
    • Other Affiliation: National Institutes of Health
  • Moore, P.L.
    • Other Affiliation: University of the Witwatersrand
  • Doria-Rose, N.A.
    • Other Affiliation: National Institutes of Health
  • Baric, R.S.
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Graham, B.S.
    • Other Affiliation: National Institutes of Health
  • McDermott, A.B.
    • Other Affiliation: National Institutes of Health
  • Douek, D.C.
    • Other Affiliation: National Institutes of Health
  • Kwong, P.D.
    • Other Affiliation: National Institutes of Health
  • Mascola, J.R.
    • Other Affiliation: National Institutes of Health
  • Sullivan, N.J.
    • Other Affiliation: National Institutes of Health
  • Misasi, J.
    • Other Affiliation: National Institutes of Health
Abstract
  • IC80 1.5 to 34.5 nanograms per milliliter). We define the structural and functional determinants of binding for all four VOC-targeting antibodies and show that combinations of two antibodies decrease the in vitro generation of escape mutants, suggesting their potential in mitigating resistance development.
  • The emergence of highly transmissible SARS-CoV-2 variants of concern (VOCs) that are resistant to therapeutic antibodies highlights the need for continuing discovery of broadly reactive antibodies. We identified four receptor binding domain-targeting antibodies from three early-outbreak convalescent donors with potent neutralizing activity against 23 variants, including the B.1.1.7, B.1.351, P.1, B.1.429, B.1.526, and B.1.617 VOCs. Two antibodies are ultrapotent, with subnanomolar neutralization titers [half-maximal inhibitory concentration (IC50) 0.3 to 11.1 nanograms per milliliter
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Resource type
  • Article
Rights statement
  • In Copyright
Journal title
  • Science
Journal volume
  • 373
Journal issue
  • 6556
Language
  • English
ISSN
  • 0036-8075
Publisher
  • American Association for the Advancement of Science

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