title: Characterization of a Novel Neutralizing Monoclonal Antibody Against Ebola Virus GP.
abstract: Ebola virus is the etiological agent of a severe hemorrhagic fever with a high mortality rate. As the only protein exposed on the surface of viral particles, the spike glycoprotein GP is the unique target for neutralizing monoclonal antibodies. In this study, we demonstrate the strong neutralization capacity of the monoclonal antibody #3327 and characterize its activity. GP residues that are required for recognition and neutralization were found to be located both in the internal fusion loop and in the receptor-binding domain. Analysis of Ebola virus entry in the presence of #3327 allows us to hypothesize that this antibody binds to the virus particle before internalization and endosomal processing of GP and likely prevents the final viral fusion step. Importantly, #3327 is able to block entry of virions bearing GP that contain the Q508 escape mutation common to a number of virus-neutralizing antibodies, and therefore provides future perspectives for treatment strategies against Ebola virus infection.
authors.affiliation: Molecular Basis of Viral Pathogenicity, CIRI, INSERM U1111-CNRS UMR5308, Université de Lyon, Université Claude Bernard Lyon 1, Ecole Normale Supérieure de Lyon, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Reynard
authors.affiliation: Molecular Basis of Viral Pathogenicity, CIRI, INSERM U1111-CNRS UMR5308, Université de Lyon, Université Claude Bernard Lyon 1, Ecole Normale Supérieure de Lyon, France.
authors.forename: Viktor E
authors.initials: VE
authors.lastname: Volchkov
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D057134:Antibodies, Neutralizing / Q000276:immunology*; D000914:Antibodies, Viral / Q000276:immunology*; D002460:Cell Line; D002522:Chlorocebus aethiops; D029043:Ebolavirus / Q000276:immunology*; D006023:Glycoproteins / Q000276:immunology; D057809:HEK293 Cells; D019142:Hemorrhagic Fever, Ebola / Q000276:immunology / Q000821:virology; D006801:Humans; D011485:Protein Binding / Q000276:immunology; D014709:Vero Cells; D014771:Virion / Q000276:immunology; D053586:Virus Internalization
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D006023:Glycoproteins
keywords: Ebola virus; filovirus; glycoprotein GP; virus neutralizing antibody