Structural Basis for a Convergent Immune Response against Ebola Virus.,Cell Host & Microbe

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Structural Basis for a Convergent Immune Response against Ebola Virus.
Cell Host & Microbe ( IF 20.6 ) Pub Date : 2020-02-06 , DOI: 10.1016/j.chom.2020.01.007
Hadas Cohen-Dvashi ₁ , Matthias Zehner ₂ , Stefanie Ehrhardt ₂ , Michael Katz ₁ , Nadav Elad ₃ , Florian Klein ₄ , Ron Diskin ₁

Affiliation

Ebola virus disease is a severe health problem in Africa. Vaccines that display the Zaire ebolavirus glycoprotein spike complex are a prime component for the effort to combat it. The VH3-15/Vλ1-40-based class of antibodies was recently discovered to be a common response in individuals who received the Ebola virus vaccines. These antibodies display attractive properties, and thus likely contribute to the efficacy of the vaccines. Here, we use cryo-EM to elucidate how three VH3-15/Vλ1-40 antibodies from different individuals target the virus and found a convergent mechanism against a partially conserved site on the spike complex. Our study rationalizes the selection of the VH3-15/Vλ1-40 germline genes for specifically targeting this site and highlights Ebolavirus species-specific sequence divergences that may restrict breadth of VH3-15/Vλ1-40-based humoral response. The results from this study could help develop improved immunization schemes and further enable the design of immunogens that would be efficacious against a broader set of Ebolavirus species.

中文翻译：

针对埃博拉病毒的免疫反应的结构基础。

埃博拉病毒病是非洲的严重健康问题。展示扎伊尔埃博拉病毒糖蛋白刺突复合物的疫苗是与之抗争的主要成分。最近发现，基于VH3-15 /Vλ1-40的抗体是接受埃博拉病毒疫苗的个体的常见反应。这些抗体显示出诱人的特性，因此可能有助于疫苗的功效。在这里，我们使用cryo-EM来阐明来自不同个体的三种VH3-15 /Vλ1-40抗体是如何靶向该病毒的，并发现了针对尖峰复合物上部分保守位点的收敛机制。我们的研究合理化了VH3-15 /Vλ1-40种系基因的选择，以专门针对该位点，并强调了埃博拉病毒种特异性序列差异，这可能会限制基于VH3-15 /Vλ1-40的体液反应的广度。这项研究的结果可能有助于开发改进的免疫方案，并进一步实现针对更广泛的埃博拉病毒种的有效免疫原设计。

更新日期：2020-02-20

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