Bispecific Antibody Affords Complete Post-Exposure Protection of Mice from Both Ebola (Zaire) and Sudan Viruses.
Bispecific Antibody Affords Complete Post-Exposure Protection of Mice from Both Ebola (Zaire) and Sudan Viruses.
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DOI：
10.1038/srep19193
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发表时间：
2016-01-13
影响因子：
4.6
通讯作者：
Lai JR
中科院分区：
文献类型：
--
作者：
Frei JC;Nyakatura EK;Zak SE;Bakken RR;Chandran K;Dye JM;Lai JR
丝状病毒（埃博拉病毒和马尔堡病毒）可引起严重的出血热。埃博拉病毒有五种;其中，埃博拉病毒（扎伊尔）和苏丹病毒（分别为EBOV和SUDV）具有高致病性，并且都引起了反复的大规模爆发。然而，EBOV和SUDV糖蛋白（GP）序列有45%的差异，因此抗原性不同。迄今为止，很少有具有交叉中和性质的抗体被描述。我们使用抗体工程来开发新的双特异性抗体（Bis-mAb），其对来自EBOV和SUDV的GP上的碱基表位具有交叉反应性。这些Bis-mAb表现出对EBOV和SUDV GP假型病毒以及真实病原体的有效中和，并赋予小鼠高度（在一种情况下为100%）的暴露后保护免受两种病毒的侵害。我们的研究表明，针对GP基础表位的单一药物足以对小鼠提供保护;此类药物可以包含在泛丝病毒治疗性抗体混合物中。
Filoviruses (Ebola and Marburg) cause severe hemorrhagic fever. There are five species of ebolavirus; among these, the Ebola (Zaire) and Sudan viruses (EBOV and SUDV, respectively) are highly pathogenic and have both caused recurring, large outbreaks. However, the EBOV and SUDV glycoprotein (GP) sequences are 45% divergent and thus antigenically distinct. Few antibodies with cross-neutralizing properties have been described to date. We used antibody engineering to develop novel bispecific antibodies (Bis-mAbs) that are cross-reactive toward base epitopes on GP from EBOV and SUDV. These Bis-mAbs exhibit potent neutralization against EBOV and SUDV GP pseudotyped viruses as well as authentic pathogens, and confer a high degree (in one case 100%) post-exposure protection of mice from both viruses. Our studies show that a single agent that targets the GP base epitopes is sufficient for protection in mice; such agents could be included in panfilovirus therapeutic antibody cocktails.