title: Identification of continuous human B-cell epitopes in the VP35, VP40, nucleoprotein and glycoprotein of Ebola virus.
abstract: Ebola virus (EBOV) is a highly virulent human pathogen. Recovery of infected patients is associated with efficient EBOV-specific immunoglobulin G (IgG) responses, whereas fatal outcome is associated with defective humoral immunity. As B-cell epitopes on EBOV are poorly defined, we sought to identify specific epitopes in four EBOV proteins (Glycoprotein (GP), Nucleoprotein (NP), and matrix Viral Protein (VP)40 and VP35). For the first time, we tested EBOV IgG+ sera from asymptomatic individuals and symptomatic Gabonese survivors, collected during the early humoral response (seven days after the end of symptoms) and the late memory phase (7-12 years post-infection). We also tested sera from EBOV-seropositive patients who had never had clinical signs of hemorrhagic fever or who lived in non-epidemic areas (asymptomatic subjects). We found that serum from asymptomatic individuals was more strongly reactive to VP40 peptides than to GP, NP or VP35. Interestingly, anti-EBOV IgG from asymptomatic patients targeted three immunodominant regions of VP40 reported to play a crucial role in virus assembly and budding. In contrast, serum from most survivors of the three outbreaks, collected a few days after the end of symptoms, reacted mainly with GP peptides. However, in asymptomatic subjects the longest immunodominant domains were identified in GP, and analysis of the GP crystal structure revealed that these domains covered a larger surface area of the chalice bowl formed by three GP1 subunits. The B-cell epitopes we identified in the EBOV VP35, VP40, NP and GP proteins may represent important tools for understanding the humoral response to this virus and for developing new antibody-based therapeutics or detection methods.
authors.affiliation: UMR 264 MIVEGEC, Institut de Recherche pour le Développement (IRD). Montpellier, France; Centre International de Recherches Médicales de Franceville, Franceville, Gabon.
authors.forename: Pierre
authors.initials: P
authors.lastname: Becquart
authors.affiliation: Centre International de Recherches Médicales de Franceville, Franceville, Gabon.
authors.forename: Tanel
authors.initials: T
authors.lastname: Mahlakõiv
authors.affiliation: Centre International de Recherches Médicales de Franceville, Franceville, Gabon.
authors.forename: Dieudonné
authors.initials: D
authors.lastname: Nkoghe
authors.affiliation: UMR 264 MIVEGEC, Institut de Recherche pour le Développement (IRD). Montpellier, France; Centre International de Recherches Médicales de Franceville, Franceville, Gabon.
authors.forename: Eric M
authors.initials: EM
authors.lastname: Leroy
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D001402:B-Lymphocytes / Q000276:immunology*; D002648:Child; D004196:Disease Outbreaks; D029043:Ebolavirus / Q000235:genetics* / Q000276:immunology; D000939:Epitopes / Q000235:genetics / Q000276:immunology; D005260:Female; D005681:Gabon; D006023:Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D019142:Hemorrhagic Fever, Ebola / Q000097:blood / Q000453:epidemiology / Q000821:virology*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins / Q000235:genetics / Q000276:immunology*; D065288:Serogroup; D014758:Viral Core Proteins / Q000235:genetics / Q000276:immunology*
chemical_list: D000939:Epitopes; D006023:Glycoproteins; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; D014758:Viral Core Proteins; C084818:nucleoprotein VP35, Ebola virus; C084819:nucleoprotein VP40, Ebola virus