美国拉霍亚免疫学研究所Erica Ollmann Saphire等研究人员合作发现，两种不同抗体对糖蛋白的不对称和非化学计量识别导致对埃博拉病毒的广泛保护。2022年3月17日，国际知名学术期刊《细胞》发表了这一成果。
研究人员表示，一些埃博拉病毒导致严重疾病的爆发。疫苗和单克隆抗体鸡尾酒疗法可用于治疗埃博拉病毒（EBOV）感染，但不包括苏丹病毒（SUDV）或其他埃博拉病毒。目前的鸡尾酒疗法含有与吸收病毒中和抗体的分泌型可溶性糖蛋白（sGP）产生交叉反应的抗体。
通过对EBOV感染幸存者的记忆B细胞进行分类，研究人员分离出两种广泛反应的抗GP单克隆抗体1C3和1C11，它们能有效地中和、保护啮齿动物免于疾病，并且缺乏sGP交叉反应。这两种抗体都能识别三聚体埃博拉病毒GP中的四级表位。1C11通过融合环连接相邻的原形体。1C3在三聚体顶点的中心有一个三方的表位。一个1C3抗原结合片段同时锚定在GP三聚体的三个受体结合位点上，而单独的1C3 paratope区域与三个原体上的相同残基有不同的相互作用。两种抗体的鸡尾酒疗法能够完全保护非人类灵长类动物免受EBOV和SUDV的感染，表明它们具有潜在的临床价值。
附：英文原文
Title: Asymmetric and non-stoichiometric glycoprotein recognition by two distinct antibodies results in broad protection against ebolaviruses
Author: Jacob C. Milligan, Carl W. Davis, Xiaoying Yu, Philipp A. Ilinykh, Kai Huang, Peter J. Halfmann, Robert W. Cross, Viktoriya Borisevich, Krystle N. Agans, Joan B. Geisbert, Chakravarthy Chennareddy, Arthur J. Goff, Ashley E. Piper, Sean Hui, Kelly C.L. Shaffer, Tierra Buck, Megan L. Heinrich, Luis M. Branco, Ian Crozier, Michael R. Holbrook, Jens H. Kuhn, Yoshihiro Kawaoka, Pamela J. Glass, Alexander Bukreyev, Thomas W. Geisbert, Gabriella Worwa, Rafi Ahmed, Erica Ollmann Saphire
Issue&Volume: 2022/03/17
Abstract: Several ebolaviruses cause outbreaks of severe disease. Vaccines and monoclonal antibodycocktails are available to treat Ebola virus (EBOV) infections, but not Sudan virus(SUDV) or other ebolaviruses. Current cocktails contain antibodies that cross-reactwith the secreted soluble glycoprotein (sGP) that absorbs virus-neutralizing antibodies.By sorting memory B cells from EBOV infection survivors, we isolated two broadly reactiveanti-GP monoclonal antibodies, 1C3 and 1C11, that potently neutralize, protect rodentsfrom disease, and lack sGP cross-reactivity. Both antibodies recognize quaternaryepitopes in trimeric ebolavirus GP. 1C11 bridges adjacent protomers via the fusionloop. 1C3 has a tripartite epitope in the center of the trimer apex. One 1C3 antigen-bindingfragment anchors simultaneously to the three receptor-binding sites in the GP trimer,and separate 1C3 paratope regions interact differently with identical residues onthe three protomers. A cocktail of both antibodies completely protected nonhuman primatesfrom EBOV and SUDV infections, indicating their potential clinical value.
DOI: 10.1016/j.cell.2022.02.023
Source: https://www.cell.com/cell/fulltext/S0092-8674(22)00203-3