来自埃博拉幸存者的完整病毒蛋白组的纵向人类抗体 repertoire 揭示了疫苗设计的保护性位点。
Longitudinal Human Antibody Repertoire against Complete Viral Proteome from Ebola Virus Survivor Reveals Protective Sites for Vaccine Design.
机构信息
Division of Viral Products, Center for Biologics Evaluation and Research (CBER), FDA, Silver Spring, MD 20871, USA.
Division of Viral Products, Center for Biologics Evaluation and Research (CBER), FDA, Silver Spring, MD 20871, USA.
出版信息
Cell Host Microbe. 2020 Feb 12;27(2):262-276.e4. doi: 10.1016/j.chom.2020.01.001.
Evolution of antibody repertoire against the Ebola virus (EBOV) proteome was characterized in an acutely infected patient receiving supportive care alone to elucidate virus-host interactions over time. Differential kinetics are observed for IgM-IgG-IgA epitope diversity, antibody binding, and affinity maturation to EBOV proteins. During acute illness, antibodies predominate to VP40 and glycoprotein (GP). At day 13 of clinical illness, a marked increase in antibody titers to most EBOV proteins and affinity maturation to GP is associated with rapid decline in viral replication and illness severity. At one year, despite undetectable virus, a diverse IgM repertoire against VP40 and GP epitopes is observed suggesting occult viral persistence. Rabbit immunization experiments identify key immunodominant sites of GP, while challenge studies in mice found these epitopes induce EBOV-neutralizing antibodies and protect against lethal EBOV challenge. This study reveals markers of viral persistence and provides promising approaches for development and evaluation of vaccines and therapeutics.
对单独接受支持性治疗的急性感染患者的埃博拉病毒 (EBOV) 蛋白质组抗体库的进化进行了表征，以阐明随时间推移的病毒-宿主相互作用。观察到 IgM-IgG-IgA 表位多样性、抗体结合和对 EBOV 蛋白的亲和力成熟的差异动力学。在急性疾病期间，抗体主要针对 VP40 和糖蛋白 (GP)。在临床疾病的第 13 天，大多数 EBOV 蛋白的抗体滴度和对 GP 的亲和力成熟显著增加，与病毒复制和疾病严重程度的快速下降相关。一年后，尽管病毒无法检测到，但仍观察到针对 VP40 和 GP 表位的多样化 IgM 库，表明存在隐匿性病毒持续存在。兔免疫实验鉴定了 GP 的关键免疫优势位点，而在小鼠的挑战研究中发现这些表位诱导产生 EBOV 中和抗体并可预防致命的 EBOV 挑战。这项研究揭示了病毒持续存在的标志物，并为疫苗和治疗药物的开发和评估提供了有希望的方法。
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