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ZMapp 减少了新鲜人宫颈阴道黏液中埃博拉病毒颗粒的扩散。

ZMapp reduces diffusion of Ebola viral particles in fresh human cervicovaginal mucus.

机构信息

UNC/NCSU Joint Department of Biomedical Engineering, Chapel Hill, NC, USA.

Division of Pharmacoengineering and Molecular Pharmaceutics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

出版信息

Emerg Microbes Infect. 2024 Dec;13(1):2352520. doi: 10.1080/22221751.2024.2352520. Epub 2024 May 16.

DOI:10.1080/22221751.2024.2352520
PMID:38713593
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11100441/
Abstract

Vaginal transmission from semen of male Ebola virus (EBOV) survivors has been implicated as a potential origin of Ebola virus disease (EVD) outbreaks. While EBOV in semen must traverse cervicovaginal mucus (CVM) to reach target cells, the behaviour of EBOV in CVM is poorly understood. CVM contains substantial quantities of IgG, and arrays of IgG bound to a virion can develop multiple Fc-mucin bonds, immobilizing the IgG/virion complex in mucus. Here, we measured the real-time mobility of fluorescent Ebola virus-like-particles (VLP) in 50 CVM specimens from 17 women, with and without ZMapp, a cocktail of 3 monoclonal IgGs against EBOV. ZMapp-mediated effective trapping of Ebola VLPs in CVM from a subset of women across the menstrual cycle, primarily those with dominant microbiota. Our work underscores the influence of the vaginal microbiome on IgG-mucin crosslinking against EBOV and identifies bottlenecks in the sexual transmission of EBOV.

摘要

精液中的埃博拉病毒（EBOV）从男性埃博拉病毒幸存者传播，被认为是埃博拉病毒病（EVD）爆发的潜在起源。虽然精液中的 EBOV 必须穿过宫颈阴道粘液（CVM）才能到达靶细胞，但 CVM 中 EBOV 的行为却知之甚少。CVM 中含有大量的 IgG，并且与病毒粒子结合的 IgG 阵列可以形成多个 Fc-粘蛋白键，使 IgG/病毒粒子复合物在粘液中固定。在这里，我们测量了来自 17 名女性的 50 份 CVM 标本中荧光埃博拉病毒样颗粒（VLP）的实时迁移率，这些标本中有的含有 ZMapp，一种针对 EBOV 的 3 种单克隆 IgG 的混合物，有的则没有。ZMapp 介导的对 Ebola VLP 的有效捕获，主要发生在具有主导微生物群的女性的月经周期中的一部分女性的 CVM 中。我们的工作强调了阴道微生物组对 EBOV 中 IgG-粘蛋白交联的影响，并确定了 EBOV 性传播中的瓶颈。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e74/11100441/ad13c70c584c/TEMI_A_2352520_F0005_OB.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e74/11100441/49b8dad5ca22/TEMI_A_2352520_F0001_OB.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e74/11100441/bf1b5afd18f9/TEMI_A_2352520_F0002_OB.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e74/11100441/755916c6aaee/TEMI_A_2352520_F0003_OB.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e74/11100441/45c06a45614e/TEMI_A_2352520_F0004_OB.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e74/11100441/ad13c70c584c/TEMI_A_2352520_F0005_OB.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e74/11100441/49b8dad5ca22/TEMI_A_2352520_F0001_OB.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e74/11100441/bf1b5afd18f9/TEMI_A_2352520_F0002_OB.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e74/11100441/755916c6aaee/TEMI_A_2352520_F0003_OB.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e74/11100441/45c06a45614e/TEMI_A_2352520_F0004_OB.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e74/11100441/ad13c70c584c/TEMI_A_2352520_F0005_OB.jpg

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本文引用的文献

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2
Characterization of an air-liquid interface primary human vaginal epithelium to study Ebola virus infection and testing of antivirals.研究埃博拉病毒感染和抗病毒药物测试的人原代阴道上皮细胞气液界面模型的建立。
Antiviral Res. 2023 Mar;211:105551. doi: 10.1016/j.antiviral.2023.105551. Epub 2023 Jan 31.
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Stable nebulization and muco-trapping properties of regdanvimab/IN-006 support its development as a potent, dose-saving inhaled therapy for COVID-19.
瑞格丹维单抗/IN-006稳定的雾化和黏液捕获特性支持其作为一种强效、节省剂量的COVID-19吸入疗法进行开发。
Bioeng Transl Med. 2022 Aug 30;8(1):e10391. doi: 10.1002/btm2.10391.
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The impact of semen testing for Ebola virus RNA on sexual behavior of male Ebola survivors in Liberia.利比里亚埃博拉幸存者精液检测埃博拉病毒 RNA 对其性行为的影响。
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Polyphenylene carboxymethylene (PPCM) in vitro antiviral efficacy against Ebola virus in the context of a sexually transmitted infection.聚对苯二甲酸亚苯基碳酸酯（PPCM）在性传播感染情况下对埃博拉病毒的体外抗病毒功效。
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Comprehensive Clinical and Laboratory Follow-up of a Female Patient With Ebola Virus Disease: Sierra Leone Ebola Virus Persistence Study.一名埃博拉病毒病女性患者的全面临床和实验室随访：塞拉利昂埃博拉病毒持续感染研究
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Ebola Virus Infection Associated with Transmission from Survivors.埃博拉病毒感染与幸存者传播有关。
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Mucosal Immunol. 2018 Sep;11(5):1477-1486. doi: 10.1038/s41385-018-0054-z. Epub 2018 Jul 9.
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