Abstract:
:Previous efforts to identify cross-neutralizing antibodies to the receptor-binding site (RBS) of ebolavirus glycoproteins have been unsuccessful, largely because the RBS is occluded on the viral surface. We report a monoclonal antibody (FVM04) that targets a uniquely exposed epitope within the RBS; cross-neutralizes Ebola (EBOV), Sudan (SUDV), and, to a lesser extent, Bundibugyo viruses; and shows protection against EBOV and SUDV in mice and guinea pigs. The antibody cocktail ZMapp™ is remarkably effective against EBOV (Zaire) but does not cross-neutralize other ebolaviruses. By replacing one of the ZMapp™ components with FVM04, we retained the anti-EBOV efficacy while extending the breadth of protection to SUDV, thereby generating a cross-protective antibody cocktail. In addition, we report several mutations at the base of the ebolavirus glycoprotein that enhance the binding of FVM04 and other cross-reactive antibodies. These findings have important implications for pan-ebolavirus vaccine development and defining broadly protective antibody cocktails.
journal_name
Cell Repjournal_title
Cell reportsauthors
Howell KA,Qiu X,Brannan JM,Bryan C,Davidson E,Holtsberg FW,Wec AZ,Shulenin S,Biggins JE,Douglas R,Enterlein SG,Turner HL,Pallesen J,Murin CD,He S,Kroeker A,Vu H,Herbert AS,Fusco ML,Nyakatura EK,Lai JR,Keck ZY,doi
10.1016/j.celrep.2016.04.026subject
Has Abstractpub_date
2016-05-17 00:00:00pages
1514-1526issue
7issn
2211-1247pii
S2211-1247(16)30439-9journal_volume
15pub_type
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