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.

中文翻译：

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针对来自埃博拉病毒幸存者的完整病毒蛋白质组的纵向人类抗体库揭示了疫苗设计的保护位点。

针对埃博拉病毒（EBOV）蛋白质组的抗体库的演变的特征是，急性感染的患者仅接受支持治疗以阐明病毒与宿主之间的相互作用。观察到IgM-IgG-IgA表位多样性，抗体结合以及对EBOV蛋白亲和力成熟的动力学差异。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，对大多数EBOV蛋白的抗体滴度显着提高，并且对GP的亲和力成熟与病毒复制和疾病严重程度的迅速下降有关。在一年的时间里，尽管检测不到病毒，但仍观察到针对VP40和GP表位的多种IgM组成，表明隐匿性病毒持续存在。兔免疫实验确定了GP的关键免疫显性位点，同时在小鼠中进行攻击研究，发现这些表位诱导了EBOV中和抗体，并防止致命的EBOV攻击。这项研究揭示了病毒持久性的标志，并为疫苗和治疗剂的开发和评估提供了有希望的方法。