title: Conservancy of mAb Epitopes in Ebolavirus Glycoproteins of Previous and 2014 Outbreaks.
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.
  
  
  CONCLUSIONS
  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.
authors: University of California San Diego, La Jolla, California, USA.
authors: Julia
authors: J
authors: Ponomarenko
authors: La Jolla Institute, La Jolla, California, USA.
authors: Kerrie
authors: K
authors: Vaughan
authors: La Jolla Institute, La Jolla, California, USA.
authors: Alessandro
authors: A
authors: Sette
authors: Bioinformatics Institute (BII), ASTAR, Singapore.
authors: Sebastian
authors: S
authors: Maurer-Stroh
keywords: EBOV; disease outbreak; ebola; ebolavirus; epitope; mAb
references: Sci Transl Med. 2013 Aug 21;5(199):199ra113
references: 23966302
references: Bioinformatics. 2011 Jun 15;27(12):1711-2
references: 21505037
references: Bioinformatics. 2009 May 1;25(9):1189-91
references: 19151095
references: Nature. 2014 Oct 2;514(7520):47-53
references: 25171469
references: J Virol. 2014 Sep;88(18):10958-62
references: 25008940
references: Proc Natl Acad Sci U S A. 2012 Oct 30;109(44):18030-5
references: 23071322
references: Nucleic Acids Res. 2010 Jan;38(Database issue):D854-62
references: 19906713
references: Methods Mol Biol. 2014;1079:131-46
references: 24170399
references: Sci Transl Med. 2012 Jun 13;4(138):138ra81
references: 22700957
references: Clin Immunol. 2011 Nov;141(2):218-27
references: 21925951
references: Bioinformatics. 2014 Oct 15;30(20):2981-2
references: 24996895
references: Science. 2000 Mar 3;287(5458):1664-6
references: 10698744
references: J Mol Biol. 2008 Jan 4;375(1):202-16
references: 18005986
references: Virus Res. 2014 Aug 30;189:254-61
references: 24930448
references: Science. 2014 Sep 12;345(6202):1369-72
references: 25214632
references: Sci Rep. 2013 Nov 28;3:3365
references: 24284388
references: Nucleic Acids Res. 2010 Jul;38(Web Server issue):W529-33
references: 20478830