title: Epitopes required for antibody-dependent enhancement of Ebola virus infection.
abstract: We have shown that antibody-dependent enhancement (ADE) of infection with Zaire Ebola virus (ZEBOV) is mediated by interaction of virus-specific antibodies with Fc receptors or complement component C1q and its receptors in vitro. ADE activities of the antisera to the viral glycoprotein (GP) were virus species specific and were primarily correlated with immunoglobulin (Ig) G2a and IgM levels but not with IgG1 levels. Interestingly, compared with ZEBOV, Reston Ebola virus (REBOV) had substantially weaker potential to induce ADE antibodies. Using monoclonal antibodies, we identified ZEBOV-specific ADE epitopes. To confirm epitope specificity, we constructed a chimeric ZEBOV GP, the ADE epitopes of which were replaced with the corresponding regions of REBOV GP. We found that mouse antisera to the chimeric ZEBOV GP showed less potential to induce ADE activity than did mouse antisera to wild-type ZEBOV GP, although they retained neutralizing activity. These data suggest that GP lacking the ADE-inducing epitopes may increase the potential of GP as a vaccine antigen.
authors.affiliation: Department of Global Epidemiology, Research Center for Zoonosis Control, Hokkaido University, Sapporo 060-0818, Japan. atakada@czc.hokudai.ac.jp
authors.forename: Ayato
authors.initials: A
authors.lastname: Takada
authors.forename: Hideki
authors.initials: H
authors.lastname: Ebihara
authors.forename: Heinz
authors.initials: H
authors.lastname: Feldmann
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Geisbert
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kawaoka
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000914:Antibodies, Viral / Q000276:immunology*; D015703:Antigens, CD / Q000276:immunology; D029043:Ebolavirus / Q000235:genetics / Q000472:pathogenicity*; D000939:Epitopes / Q000032:analysis; D049452:Green Fluorescent Proteins / Q000032:analysis / Q000235:genetics; D019142:Hemorrhagic Fever, Ebola / Q000145:classification / Q000276:immunology*; D006801:Humans; D007114:Immunization; D051379:Mice; D011994:Recombinant Proteins / Q000032:analysis; D014162:Transfection; D014721:Vesicular stomatitis Indiana virus / Q000235:genetics
chemical_list: D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D015703:Antigens, CD; D000939:Epitopes; D011994:Recombinant Proteins; D049452:Green Fluorescent Proteins