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

作者：Howell Katie A; Qiu Xiangguo; Brannan Jennifer M; Bryan Christopher; Davidson Edgar; Holt**erg 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 H; Saphire Erica Ollmann; Zeitlin Larry; Ward Andrew B; Chandran Kartik

来源：Cell Reports, 2016, 15(7): 1514-1526.

DOI：10.1016/j.celrep.2016.04.026

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 (TM) is remarkably effective against EBOV (Zaire) but does not cross-neutralize other ebolaviruses. By replacing one of the ZMapp (TM) 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.

• 出版日期2016-5-17