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Published on: March 24, 2017
Conservancy of mAb Epitopes in Ebolavirus Glycoproteins of Previous and 2014 Outbreaks
Julia Ponomarenko1, Kerrie Vaughan2, Alessandro Sette2
1University of California San Diego, La Jolla, California, USA.
Background:
Several monoclonal antibodies (mAb) are being evaluated as treatment options for the current 2014 Ebola outbreak. But they were derived from and tested for protection against the older 1976 Mayinga or 1995 Kikwit Zaire Ebolaviruses (EBOV). The EBOV sequences reported for the current outbreak contain several mutations whose significance remained to be established.
Methods:
We analyzed sequence and structural conservation of the Ebolavirus glycoprotein (GP) epitopes for all experimentally identified protective mAbs published to date.
Results:
The conservancy analysis of protective mAb epitopes in the Ebolavirus glycoprotein sequences spanning all Ebola virus lineages since 1976 showed that conservancy within the Zaire EBOV lineage was high, with only one immunodominant epitope of mAb 13F6-1-2 acquiring two novel mutations in the 2014 outbreak that might potentially change the antibody specificity and neutralization activity. However, the conservation to other Ebola viruses was unexpectedly low.
Conclusion:
Low conservancy of Zaire EBOV mAb epitopes to other EBOV lineages suggests that these epitopes are not indispensable for viral fitness, and that alternative mAbs could be developed to broadly target all EBOV. However, average percent sequence identity of the epitopes for mAbs used in current cocktails to the Zaire EBOV is high with only one epitope differing in the 2014 outbreak. These data bode well for general usefulness of these antibodies in the context of the current outbreak.
Insights
Monoclonal antibodies (mAbs) targeting Ebola virus (EBOV) show high conservation within the Zaire EBOV lineage. However, mutations in the 2014 outbreak may affect antibody specificity, necessitating broad-spectrum EBOV treatments.
Area of Science:
- Virology
- Immunology
- Structural Biology
Background:
- Monoclonal antibodies (mAbs) are under investigation for treating the 2014 Ebola virus outbreak (EBOV).
- Existing mAbs were developed against older EBOV strains (1976, 1995), and the 2014 outbreak sequences show mutations.
- The impact of these mutations on mAb efficacy remains unclear.
Purpose of the Study:
- To analyze the sequence and structural conservation of Ebolavirus glycoprotein (GP) epitopes targeted by protective mAbs.
- To assess the potential impact of mutations in the 2014 EBOV outbreak on the efficacy of existing mAbs.
Main Methods:
- Sequence and structural analysis of Ebolavirus GP epitopes.
- Comparison of epitope conservation across different EBOV lineages and outbreak strains.
Main Results:
- Epitope conservation within the Zaire EBOV lineage is high.
- One key epitope targeted by mAb 13F6-1-2 shows mutations in the 2014 outbreak, potentially altering antibody specificity and neutralization.
- Epitope conservation across different EBOV lineages is unexpectedly low.
Conclusions:
- Low cross-lineage conservation suggests Zaire EBOV mAb epitopes are not essential for viral fitness.
- Development of alternative mAbs targeting conserved epitopes could provide broader EBOV protection.
- Current mAbs show high sequence identity to the 2014 Zaire EBOV strain, indicating potential usefulness in the current outbreak.
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