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用 EBOTAb(一种纯化的绵羊 IgG 产品)对感染致死剂量埃博拉病毒的非人类灵长类动物进行暴露后治疗。

Post-exposure treatment of non-human primates lethally infected with Ebola virus with EBOTAb, a purified ovine IgG product.

机构信息

National Infection Service, Public Health England, Porton Down, Salisbury, Wiltshire, SP4 0JG, UK.

Laboratoire P4, INSERM Jean Merieux, 21 Avenue Tony Garnier, Lyon, France.

出版信息

Sci Rep. 2017 Jun 22;7(1):4099. doi: 10.1038/s41598-017-03910-7.

DOI:10.1038/s41598-017-03910-7
PMID:28642489
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5481440/
Abstract

Despite sporadic outbreaks of Ebola virus (EBOV) over the last 4 decades and the recent public health emergency in West Africa, there are still no approved vaccines or therapeutics for the treatment of acute EBOV disease (EVD). In response to the 2014 outbreak, an ovine immunoglobulin therapy was developed, termed EBOTAb. After promising results in the guinea pig model of EBOV infection, EBOTAb was tested in the cynomolgus macaque non-human primate model of lethal EBOV infection. To ensure stringent therapeutic testing conditions to replicate likely clinical usage, EBOTAb was first delivered 1, 2 or 3 days post-challenge with a lethal dose of EBOV. Results showed a protective effect of EBOTAb given post-exposurally, with survival rates decreasing with increasing time after challenge. Viremia results demonstrated that EBOTAb resulted in a decreased circulation of EBOV in the bloodstream. Additionally, assay of liver enzymes and histology analysis of local tissues identified differences between EBOTAb-treated and untreated groups. The results presented demonstrate that EBOTAb conferred protection against EBOV when given post-exposure and should be explored and developed further as a potential intervention strategy for future outbreaks, which are likely to occur.

摘要

尽管在过去的 40 年中埃博拉病毒(EBOV)偶有爆发,并且西非最近发生了公共卫生紧急事件,但仍没有批准用于治疗急性 EBOV 疾病(EVD)的疫苗或疗法。针对 2014 年的爆发,开发了一种绵羊免疫球蛋白疗法,称为 EBOTAb。在豚鼠 EBOV 感染模型中取得了令人鼓舞的结果后,在食蟹猴非人类灵长类动物致死性 EBOV 感染模型中测试了 EBOTAb。为了确保严格的治疗测试条件以复制可能的临床使用情况,首先在暴露后 1、2 或 3 天用致死剂量的 EBOV 进行 EBOTAb 给药。结果表明,EBOTAb 在暴露后给药具有保护作用,随着挑战后时间的增加,存活率降低。病毒血症结果表明,EBOTAb 导致血液中 EBOV 的循环减少。此外,对肝酶的检测和局部组织的组织学分析鉴定了 EBOTAb 治疗组和未治疗组之间的差异。提出的结果表明,EBOTAb 在暴露后给药可提供针对 EBOV 的保护作用,并且应该进一步探索和开发,作为未来可能发生的爆发的潜在干预策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/929b/5481440/e9738255bfb8/41598_2017_3910_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/929b/5481440/c04a928befe8/41598_2017_3910_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/929b/5481440/79336a243473/41598_2017_3910_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/929b/5481440/716fda7003e6/41598_2017_3910_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/929b/5481440/4b5346543c03/41598_2017_3910_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/929b/5481440/3c90b5a02533/41598_2017_3910_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/929b/5481440/a97db873b55a/41598_2017_3910_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/929b/5481440/e9738255bfb8/41598_2017_3910_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/929b/5481440/c04a928befe8/41598_2017_3910_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/929b/5481440/79336a243473/41598_2017_3910_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/929b/5481440/716fda7003e6/41598_2017_3910_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/929b/5481440/4b5346543c03/41598_2017_3910_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/929b/5481440/3c90b5a02533/41598_2017_3910_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/929b/5481440/a97db873b55a/41598_2017_3910_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/929b/5481440/e9738255bfb8/41598_2017_3910_Fig7_HTML.jpg

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