Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Cell. 2018 Aug 9;174(4):938-952.e13. doi: 10.1016/j.cell.2018.07.033.
Antibodies are promising post-exposure therapies against emerging viruses, but which antibody features and in vitro assays best forecast protection are unclear. Our international consortium systematically evaluated antibodies against Ebola virus (EBOV) using multidisciplinary assays. For each antibody, we evaluated epitopes recognized on the viral surface glycoprotein (GP) and secreted glycoprotein (sGP), readouts of multiple neutralization assays, fraction of virions left un-neutralized, glycan structures, phagocytic and natural killer cell functions elicited, and in vivo protection in a mouse challenge model. Neutralization and induction of multiple immune effector functions (IEFs) correlated most strongly with protection. Neutralization predominantly occurred via epitopes maintained on endosomally cleaved GP, whereas maximal IEF mapped to epitopes farthest from the viral membrane. Unexpectedly, sGP cross-reactivity did not significantly influence in vivo protection. This comprehensive dataset provides a rubric to evaluate novel antibodies and vaccine responses and a roadmap for therapeutic development for EBOV and related viruses.
抗体是有前途的针对新兴病毒的暴露后治疗方法，但哪种抗体特征和体外检测最能预测保护作用尚不清楚。我们的国际联盟使用多学科检测方法系统地评估了针对埃博拉病毒（EBOV）的抗体。对于每种抗体，我们评估了病毒表面糖蛋白（GP）和分泌糖蛋白（sGP）上识别的表位、多种中和检测的结果、未被中和的病毒粒子的比例、聚糖结构、吞噬细胞和自然杀伤细胞功能的诱导，以及在小鼠挑战模型中的体内保护作用。中和作用和多种免疫效应功能（IEFs）的诱导与保护作用相关性最强。中和作用主要通过内体切割的 GP 上保持的表位发生，而最大的 IEF 则映射到距离病毒膜最远的表位。出乎意料的是，sGP 的交叉反应性并没有显著影响体内保护作用。这个全面的数据集为评估新型抗体和疫苗反应提供了一个标准，并为 EBOV 和相关病毒的治疗开发提供了一个路线图。
