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

IF 8.4 2区医学 Q1 IMMUNOLOGY Emerging Microbes & Infections Pub Date : 2024-12-01 Epub Date: 2024-05-16 DOI:10.1080/22221751.2024.2352520

Alison Schaefer, Bing Yang, Holly A Schroeder, Dimple Harit, Mike S Humphry, Larry Zeitlin, Kevin J Whaley, Jacques Ravel, William A Fischer, Samuel K Lai

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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 Lactobacillus crispatus 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.

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ZMapp 可减少埃博拉病毒颗粒在新鲜人体宫颈阴道粘液中的扩散。

摘要男性埃博拉病毒（EBOV）幸存者的精液经阴道传播被认为是埃博拉病毒病（EVD）爆发的潜在来源。虽然精液中的埃博拉病毒必须穿过宫颈阴道粘液（CVM）才能到达靶细胞，但人们对埃博拉病毒在CVM中的行为却知之甚少。CVM中含有大量IgG，与病毒结合的IgG阵列可形成多个Fc-粘蛋白键，将IgG/病毒复合物固定在粘液中。在这里，我们测量了 17 名女性的 50 份 CVM 标本中荧光埃博拉病毒样颗粒（VLP）的实时流动性，包括使用和不使用 ZMapp（一种由 3 种抗 EBOV 单克隆 IgG 组成的鸡尾酒）的情况。ZMapp介导的埃博拉VLP在整个月经周期中有效捕获了一部分女性的CVM，主要是那些以脆片乳杆菌为优势微生物群的女性。我们的工作强调了阴道微生物群对抗击 EBOV 的 IgG-粘蛋白交联的影响，并确定了 EBOV 性传播的瓶颈。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Emerging Microbes & Infections IMMUNOLOGY-MICROBIOLOGY

CiteScore

26.20

自引率

2.30%

发文量

276

审稿时长

20 weeks

期刊介绍： Emerging Microbes & Infections is a peer-reviewed, open-access journal dedicated to publishing research at the intersection of emerging immunology and microbiology viruses. The journal's mission is to share information on microbes and infections, particularly those gaining significance in both biological and clinical realms due to increased pathogenic frequency. Emerging Microbes & Infections is committed to bridging the scientific gap between developed and developing countries. This journal addresses topics of critical biological and clinical importance, including but not limited to: - Epidemic surveillance - Clinical manifestations - Diagnosis and management - Cellular and molecular pathogenesis - Innate and acquired immune responses between emerging microbes and their hosts - Drug discovery - Vaccine development research Emerging Microbes & Infections invites submissions of original research articles, review articles, letters, and commentaries, fostering a platform for the dissemination of impactful research in the field.