Integrated Research Facility at Fort Detrick, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, Maryland, United States of America.
United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland, United States of America.
PLoS One. 2021 Jan 7;16(1):e0245024. doi: 10.1371/journal.pone.0245024. eCollection 2021.
Ebola virus (EBOV), a member of the mononegaviral family Filoviridae, causes severe disease associated with high lethality in humans. Despite enormous progress in development of EBOV medical countermeasures, no anti-EBOV treatment has been approved. We designed an immunotoxin in which a single-chain variable region fragment of the EBOV glycoprotein-specific monoclonal antibody 6D8 was fused to the effector domains of Pseudomonas aeruginosa exotoxin A (PE38). This immunotoxin, 6D8-PE38, bound specifically to cells expressing EBOV glycoproteins. Importantly, 6D8-PE38 targeted EBOV-infected cells, as evidenced by inhibition of infectious EBOV production from infected cells, including primary human macrophages. The data presented here provide a proof of concept for immunotoxin-based targeted killing of infected cells as a potential antiviral intervention for Ebola virus disease.
埃博拉病毒（EBOV）是单负链病毒科丝状病毒属的一员，可导致人类发生严重疾病，并伴有高死亡率。尽管在开发埃博拉病毒医疗对策方面取得了巨大进展，但仍没有批准任何抗埃博拉病毒的治疗方法。我们设计了一种免疫毒素，其中埃博拉病毒糖蛋白特异性单克隆抗体 6D8 的单链可变区片段与铜绿假单胞菌外毒素 A（PE38）的效应结构域融合。这种免疫毒素 6D8-PE38 特异性结合表达埃博拉病毒糖蛋白的细胞。重要的是，6D8-PE38 靶向感染了埃博拉病毒的细胞，这一点可通过抑制感染细胞产生感染性埃博拉病毒来证明，包括原代人巨噬细胞。这里呈现的数据为基于免疫毒素的靶向杀伤感染细胞作为埃博拉病毒病的一种潜在抗病毒干预措施提供了概念验证。
