Immunity
Volume 49, Issue 2, 21 August 2018, Pages 363-374.e10
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Article
Multifunctional Pan-ebolavirus Antibody Recognizes a Site of Broad Vulnerability on the Ebolavirus Glycoprotein

https://doi.org/10.1016/j.immuni.2018.06.018Get rights and content
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Highlights

  • Broad human antibody recognizes a quaternary site of vulnerability on ebolavirus GP

  • The antibody possesses pan-ebolavirus neutralizing and protective capacity

  • The antibody mediates protection principally by direct virus neutralization

  • The antibody uses several mechanisms for contributing to broad immunity

Summary

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.

Keywords

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

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