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首页 » Science报道 » Science:实验性的埃博拉病毒抗体或可帮助猕猴抵御病毒感染

Science:实验性的埃博拉病毒抗体或可帮助猕猴抵御病毒感染

来源:生物谷 2016-03-02 20:25

图片来源:medicalxpress.com

2016年3月2日 讯 /生物谷BIOON/ --近日,一项发表于国际杂志Science上的研究论文中,来自美国国家过敏症和传染病研究所的科学家等机构通过研究发现,一种分离自埃博拉病毒幸存者机体中可以抵御病毒的单克隆抗体,或可有效保护感染埃博拉病毒5天后的非人类灵长类动物,目前这种抗体症进一步在人类机体中测试观察其是否可以作为一种抵御埃博拉病毒的潜在疗法。

2014至2015年埃博拉病毒在西非肆虐,至少造成1.1万人死亡,而且目前国际上并没有批准的可有效治疗埃博拉病毒感染的疗法。文章中,研究者对1985年在刚果民主共和国Kikwit爆发的埃博拉病毒疫情中的幸存者进行研究,研究者获取幸存者的血液并且对血液样本进行检测,发现幸存者机体中的存留的抗体可以抵御埃博拉病毒;随后来自瑞士生物医药研究所的研究者分离出了特殊的抗体,并以此作为治疗埃博拉病毒的潜在疗法,来自美国陆军传染病医学研究所的研究者将致死剂量的扎伊尔埃波拉病毒注射到四只猕猴机体中,等待5天后再对其中三只猕猴通过静脉每日注射名为mAb114的单克隆抗体,持续三天进行注射后,研究者发现,治疗组猕猴依然存活着,而且机体并无埃博拉感染症状,相比较而言,未进行治疗的猕猴却在第九天死亡了。

随后美国国家过敏症和传染病研究所和达特茅斯学院的科学家研究了单克隆抗体mAb114如何中和埃博拉病毒,并且揭示了该抗体如何结合到埃博拉病毒糖蛋白的核心区域,从而阻断其同人类细胞受体的相互作用;此前研究者发现,一般抗体并不能到达名为受体结合区域的埃博拉病毒糖蛋白区域,因为这块区域完全被病毒掩藏了,而且仅在病毒进入细胞后5天才会暴露出来。

本文研究中,研究人员首次阐明这种特殊的单克隆抗体可以通过病毒和细胞受体间的相互作用来中和病毒,此前就有证据阐明埃博拉病毒的新型易感位点,最后研究者表明,单克隆抗体mAb114或许可以作为一种潜在疗法来用于后期深入研究和探索。(生物谷Bioon.com)

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Structural and molecular basis for Ebola virus neutralization by protective human antibodies

John Misasi1,5,8,*, Morgan S. A. Gilman2,*, Masaru Kanekiyo1,*, Miao Gui4,*, Alberto Cagigi1, Sabue Mulangu1, Davide Corti6, Julie E. Ledgerwood1, Antonio Lanzavecchia6,9, James Cunningham5, Jean Jacques Muyembe-Tamfun7, Ulrich Baxa3, Barney S. Graham1, Ye Xiang4,†,‡, Nancy J. Sullivan1,†,‡, Jason S. McLellan2,†

Ebola virus causes hemorrhagic fever with a high mortality rate and for which there is no approved therapy. Two human monoclonal antibodies, mAb100 and mAb114, in combination, protect nonhuman primates against all signs of Ebola virus disease, including viremia. Here, we demonstrate that mAb100 recognizes the base of the Ebola virus glycoprotein (GP) trimer, occludes access to the cathepsin-cleavage loop, and prevents the proteolytic cleavage of GP that is required for virus entry. We show that mAb114 interacts with the glycan cap and inner chalice of GP, remains associated following proteolytic removal of the glycan cap, and inhibits binding of cleaved GP to its receptor. These results define the basis of neutralization for two protective antibodies and may facilitate development of therapies and vaccines.

Protective monotherapy against lethal Ebola virus infection by a potently neutralizing antibody

Davide Corti1,2,*, John Misasi3,*, Sabue Mulangu3, Daphne A. Stanley3, Masaru Kanekiyo3, Suzanne Wollen4, Aurélie Ploquin3, Nicole A. Doria-Rose3, Ryan P. Staupe3, Michael Bailey3, Wei Shi3, Misook Choe3, Hadar Marcus3, Emily A. Thompson3, Alberto Cagigi3, Chiara Silacci1, Blanca Fernandez-Rodriguez1, Laurent Perez1, Federica Sallusto1, Fabrizia Vanzetta2, Gloria Agatic2, Elisabetta Cameroni2, Neville Kisalu5,†, Ingelise Gordon3, Julie E. Ledgerwood3, John R. Mascola3, Barney S. Graham3, Jean-Jacques Muyembe-Tamfun5, John C. Trefry4,‡, Antonio Lanzavecchia1,6,‡, Nancy J. Sullivan3,‡,§

Ebola virus disease in humans is highly lethal, with case fatality rates ranging from 25-90%. There is no licensed treatment or vaccine against the virus, underscoring the need for efficacious countermeasures. Here, we demonstrate that a human survivor of the 1995 Kikwit Ebola virus disease outbreak maintained circulating antibodies against the Ebola virus surface glycoprotein for more than a decade after infection. From this survivor we isolated monoclonal antibodies (mAb) that neutralize recent and previous outbreak variants of Ebola virus, and mediate antibody-dependent cell-mediated cytotoxicity in vitro. Strikingly, monotherapy with mAb114 protected macaques when given as late as five days after challenge. Treatment with a single human mAb suggests a simplified therapeutic strategy for human Ebola infection may be possible.

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