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

Authors: Gilchuk, Pavlo; Kuzmina, Natalia; Ilinykh, Philipp A; Huang, Kai; Gunn, Bronwyn M; Bryan, Aubrey; Davidson, Edgar; +25 Authors
APC: 4,550.23 EUR

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

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.

Keywords

Male, THP-1 Cells, Antibodies, Viral, Ebola hemorrhagic fever, Jurkat Cells, Mice, Monoclonal, Chlorocebus aethiops, Viral, Neutralizing, Inbred BALB C, glycoproteins, Antibodies, Monoclonal, 3T3 Cells, Ebolavirus, Infectious Diseases, Medical Microbiology, Ebola, Drosophila, Female, monoclonal antibodies, Biotechnology, Adult, 570, Knockout, Immunology, Guinea Pigs, CHO Cells, Antibodies, Article, Cell Line, Rare Diseases, Cricetulus, heterologous immunity, Biodefense, Animals, Humans, neutralizing antibodies, Vero Cells, ebolavirus, Glycoproteins, Biomedical and Clinical Sciences, Animal, Prevention, Ferrets, epitopes, Hemorrhagic Fever, Ebola, Antibodies, Neutralizing, epitope mapping, Disease Models, Animal, Emerging Infectious Diseases, Orphan Drug, Good Health and Well Being, cross protection, Immunoglobulin G, Disease Models, Hemorrhagic Fever, Immunization, viral antibodies

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    selected citations
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    This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    66
    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Top 10%
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    Top 10%
    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Top 1%
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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
66
Top 10%
Top 10%
Top 1%
Green
hybrid