Epitopes required for antibody-dependent enhancement of Ebola virus infection

Ayato Takada, Hideki Ebihara, Heinz Feldmann, Thomas W. Geisbert, Yoshihiro Kawaoka

Research output: Contribution to journalArticle

49 Citations (Scopus)

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.

Original languageEnglish (US)
JournalJournal of Infectious Diseases
Volume196
Issue numberSUPPL. 2
DOIs
StatePublished - Nov 15 2007
Externally publishedYes

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Ebola Hemorrhagic Fever
Antibody-Dependent Enhancement
Ebolavirus
Epitopes
Glycoproteins
Immune Sera
Complement C1q
Viruses
Fc Receptors
Antibodies
Immunoglobulin M
Immunoglobulins
Vaccines
Immunoglobulin G
Monoclonal Antibodies

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Immunology

Cite this

Epitopes required for antibody-dependent enhancement of Ebola virus infection. / Takada, Ayato; Ebihara, Hideki; Feldmann, Heinz; Geisbert, Thomas W.; Kawaoka, Yoshihiro.

In: Journal of Infectious Diseases, Vol. 196, No. SUPPL. 2, 15.11.2007.

Research output: Contribution to journalArticle

Takada, Ayato ; Ebihara, Hideki ; Feldmann, Heinz ; Geisbert, Thomas W. ; Kawaoka, Yoshihiro. / Epitopes required for antibody-dependent enhancement of Ebola virus infection. In: Journal of Infectious Diseases. 2007 ; Vol. 196, No. SUPPL. 2.
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