Abstract
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.
Highlights
IntroductionGire et al characterized the sequence diversity within the 2014 Ebola virus (EBOV) outbreak[1] and identified several novel mutations
Gire et al characterized the sequence diversity within the 2014 Ebola virus (EBOV) outbreak[1] and identified several novel mutations. One effect these mutations could have is to alter epitope regions that could be critical for the current situation as drug cocktails comprising monoclonal antibodies are being tested for Ebola disease treatment
As of September, 2014, analysis of the Ebola GP protein epitopes reported in the Immune Epitope Database (IEDB) and identified using assays demonstrating in vitro correlates of protection or in vivo survival assays, so-called ‘functional epitopes,’ revealed ten epitopes for nine monoclonal antibodies (mAb) (Fig. 1)
Summary
Gire et al characterized the sequence diversity within the 2014 Ebola virus (EBOV) outbreak[1] and identified several novel mutations One effect these mutations could have is to alter epitope regions that could be critical for the current situation as drug cocktails comprising monoclonal antibodies (mAbs) are being tested for Ebola disease treatment. Six monoclonal antibodies (mAb) comprising the three cocktails, ZMab, ZMapp, and MB-003, have being evaluated as treatment options for Ebola2,3,4,5,6,7,8 These mAbs were derived from and tested for protection against the older 1976 Mayinga or 1995 Kikwit Zaire Ebolaviruses. Several monoclonal antibodies (mAb) are being evaluated as treatment options for the current 2014 Ebola outbreak 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
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
