MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DS, UK.
Jenner Institute, University of Oxford, Old Road Campus Research Building, Oxford OX3 7DQ, UK.
Cell Rep. 2019 Apr 2;27(1):172-186.e7. doi: 10.1016/j.celrep.2019.03.020.
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.
我们描述了从接种表达埃博拉病毒糖蛋白（EBOV GP）的重组腺病毒并加强接种改良安卡拉牛痘病毒的人类志愿者中分离出的治疗性单克隆抗体。从外周血 B 细胞中分离出的 82 种抗体中，几乎有一半能中和 GP 假型流感病毒。抗体反应在基因使用和表位识别方面具有多样性。尽管在序列上接近 germline，但具有纳摩尔至皮摩尔范围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，也被发现。它们识别粘蛋白样结构域、聚糖帽、受体结合区域和糖蛋白的基部。在 EBOV 感染的第 3 天给予针对后三个非重叠表位的四种抗体的交叉反应鸡尾酒，完全保护了豚鼠。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。
Zotero 插件