Multifunctional Pan-ebolavirus Antibody Recognizes a Site of Broad Vulnerability on the Ebolavirus Glycoprotein

Pavlo Gilchuk, Natalia Kuzmina, Philipp A. Ilinykh, Kai Huang, Bronwyn M. Gunn, Aubrey Bryan, Edgar Davidson, Benjamin J. Doranz, Hannah L. Turner, Marnie L. Fusco, Matthew S. Bramble, Nicole A. Hoff, Elad Binshtein, Nurgun Kose, Andrew I. Flyak, Robin Flinko, Chiara Orlandi, Robert Carnahan, Erica H. Parrish, Alexander M. SevyRobin G. Bombardi, Prashant K. Singh, Patrick Mukadi, Jean Jacques Muyembe-Tamfum, Melanie D. Ohi, Erica Ollmann Saphire, George K. Lewis, Galit Alter, Andrew B. Ward, Anne W. Rimoin, Alexander Bukreyev, James E. Crowe

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Ebolaviruses cause severe disease in humans, and identification of monoclonal antibodies (mAbs) that are effective against multiple ebolaviruses are important for therapeutics development. Here we describe a distinct class of broadly neutralizing human mAbs with protective capacity against three ebolaviruses infectious for humans: Ebola (EBOV), Sudan (SUDV), and Bundibugyo (BDBV) viruses. We isolated mAbs from human survivors of ebolavirus disease and identified a potent mAb, EBOV-520, which bound to an epitope in the glycoprotein (GP) base region. EBOV-520 efficiently neutralized EBOV, BDBV, and SUDV and also showed protective capacity in relevant animal models of these infections. EBOV-520 mediated protection principally by direct virus neutralization and exhibited multifunctional properties. This study identified a potent naturally occurring mAb and defined key features of the human antibody response that may contribute to broad protection. This multifunctional mAb and related clones are promising candidates for development as broadly protective pan-ebolavirus therapeutic molecules. Ebola virus, a member of the Filoviridae family, causes severe disease in humans. Gilchuk et al. isolated and characterized broadly neutralizing human monoclonal antibodies active against all three clinically relevant ebolavirus species. Potent monoclonal antibody EBOV-520 binds to the glycoprotein base region, acts principally by direct virus neutralization, and exploits several mechanisms for contributing to pan-ebolavirus protective immunity.

Original languageEnglish (US)
Pages (from-to)363-374.e10
JournalImmunity
Volume49
Issue number2
DOIs
StatePublished - Aug 21 2018

    Fingerprint

Keywords

  • cross protection
  • Ebola hemorrhagic fever
  • ebolavirus
  • epitope mapping
  • epitopes
  • glycoproteins
  • heterologous immunity
  • monoclonal antibodies
  • neutralizing antibodies
  • viral antibodies

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Cite this

Gilchuk, P., Kuzmina, N., Ilinykh, P. A., Huang, K., Gunn, B. M., Bryan, A., Davidson, E., Doranz, B. J., Turner, H. L., Fusco, M. L., Bramble, M. S., Hoff, N. A., Binshtein, E., Kose, N., Flyak, A. I., Flinko, R., Orlandi, C., Carnahan, R., Parrish, E. H., ... Crowe, J. E. (2018). Multifunctional Pan-ebolavirus Antibody Recognizes a Site of Broad Vulnerability on the Ebolavirus Glycoprotein. Immunity, 49(2), 363-374.e10. https://doi.org/10.1016/j.immuni.2018.06.018