We describe therapeutic monoclonal antibodies isolated from human volunteers vaccinated with recombinant adenovirus expressing Ebola virus glycoprotein (EBOV GP) and boosted with modified vaccinia virus Ankara. Among 82 antibodies isolated from peripheral blood B cells, almost half neutralized GP pseudotyped influenza virus. The antibody response was diverse in gene usage and epitope recognition. Although close to germline in sequence, neutralizing antibodies with binding affinities in the nano- to pico-molar range, similar to "affinity matured" antibodies from convalescent donors, were found. They recognized the mucin-like domain, glycan cap, receptor binding region, and the base of the glycoprotein. A cross-reactive cocktail of four antibodies, targeting the latter three non-overlapping epitopes, given on day 3 of EBOV infection, completely protected guinea pigs. This study highlights the value of experimental vaccine trials as a rich source of therapeutic human monoclonal antibodies.

中文翻译：

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源自接种疫苗的人的埃博拉病毒感染的治疗性单克隆抗体。

我们描述了从表达埃博拉病毒糖蛋白（EBOV GP）的重组腺病毒接种并经修饰的痘苗病毒安卡拉加强免疫的人类志愿者中分离出的治疗性单克隆抗体。从外周血B细胞分离的82种抗体中，几乎有一半中和了GP假型流感病毒。抗体反应在基因使用和表位识别方面各不相同。尽管在序列上接近种系，但发现了具有在纳摩尔至皮摩尔范围内的结合亲和力的中和抗体，类似于来自恢复期供体的“亲和力成熟”抗体。他们认识到粘蛋白样结构域，聚糖帽，受体结合区和糖蛋白的碱基。在EBOV感染的第3天给予四种抗体的交叉反应性混合物，靶向后三种不重叠的表位，完全保护的豚鼠。这项研究强调了实验性疫苗试验作为治疗性人类单克隆抗体的丰富来源的价值。