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Epitopes required for antibody-dependent enhancement of Ebola virus infection

  1. Author:
    Takada, A.
    Ebihara, H.
    Feldmann, H.
    Geisbert, T. W.
    Kawaoka, Y.

  2. Author Address

    Hokkaido Univ, Dept Global Epidemiol, Res Ctr Zoonosis Control, Sapporo, Hokkaido 0600818, Japan. Univ Tokyo, Div Virol, Dept Microbiol & Immunol, Tokyo, Japan. Univ Tokyo, Inst Med Sci, Int Res Ctr Infect Dis, Tokyo, Japan. Japan Sci & Technol Agcy, Core Res Evolut Sci & Technol, Tokyo, Saitama, Japan. Publ Hlth Agcy Canada, Natl Microbiol Lab, Special Pathogens Program, Winnipeg, MB, Canada. Univ Manitoba, Dept Med Microbiol, Winnipeg, MB, Canada. NIH, NIAID, Integrated Res Facil, Ft Detrick, MD USA. Univ Wisconsin, Sch Vet Med, Dept Pathobiol Sci, Madison, WI 53706 USA.;Takada, A, Hokkaido Univ, Dept Global Epidemiol, Res Ctr Zoonosis Control, Sapporo, Hokkaido 0600818, Japan.;atakada@czc.hokudai.ac.jp
    1. Year: 2007
    2. Date: Nov
  2. Journal: Journal of Infectious Diseases
    1. 196
    2. Pages: S347-S356
  4. Type of Article: Article
  5. ISSN: 0022-1899
  1. 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.

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External Sources

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  2. DOI: 10.1086/520581
  3. View record in Web of Science®
  4. WOS: 000251090400033

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