Accession Number : AD1009500

Title :   Antibody Treatment of Ebola and Sudan Virus Infection via a Uniquely Exposed Epitope within the Glycoprotein Receptor Binding Site

Descriptive Note : Journal Article

Corporate Author : USAMRIID Frederick United States

Personal Author(s) : Howell, Katie A ; Qiu,Xiangguo ; Brannan,Jenifer M ; Bryan,Christopher ; Davidson,Edgar ; Holtsberg,Frederick W ; Wec,Anna Z ; Shulenin,Sergey ; Biggins,Julia E ; Douglas,Robin ; Enterlein,Sven G ; Turner,Hannah L ; Pallesen,Jesper ; Murin,Charles D ; He,Shihua ; Kroeker,Andrea ; Vu,Hong ; Herbert,Andrew S ; Fusco,Marnie L ; Nyakatura,Elisabeth K ; Lai,Jonathan R ; Keck,Zhen-Yong ; Foung,Steven K ; Saphire,Erica O ; Zeitlin,Larry ; Ward,Andrew B ; Chandran,Kartik ; Doranz,Benjamin J ; Kobinger,Gary P ; Dye,John M ; Aman,M J

Full Text :

Report Date : 14 Jun 2016

Pagination or Media Count : 42

Abstract : The conserved receptor binding site (RBS) of filovirus glycoproteins represents a potential target for cross-neutralizing antibodies. However, access to the RBS is largely occluded on the surface of ebolaviruses. Here we report a monoclonal antibody (FVM04) reactive to a uniquely exposed epitope within the RBS. FVM04 blocks glycoprotein interaction with the endosomal receptor NPC-1, cross neutralizes Ebola (EBOV), Sudan (SUDV), and Bundibugyo viruses, and protects mice and guinea pigs against EBOV and SUDV infections. The antibody cocktail ZMappTM is remarkably effective against EBOV (Zaire) but lacks cross-reactivity to other ebolaviruses. Replacing one of the ZMappTM components by FVM04 retained the anti-EBOV efficacy while extending the breadth of protection to SUDV. Furthermore, we report that exposure of several cross-reactive epitopes can be modulated by specific point mutations within the base of the ebolavirus glycoprotein. These findings have major implications for both development of pan-ebolavirus vaccines and defining broadly protective antibody cocktails.

Descriptors :   ebola virus , antibodies , glycoprotein , vaccines

Distribution Statement : APPROVED FOR PUBLIC RELEASE