ABSTRACT Ebola virus (EBOV), the causative pathogen of the deadly Ebola virus disease (EVD), can be transmitted via contact with EVD patients, including sexual contact with EVD survivors. At present, no licensed vaccine or therapeutic is available. In this study, we compared eight anhydride-modified proteins for their entry-inhibitory activity against the pseudovirus (PsV) carrying the envelope glycoprotein (GP) of the EBOV Zaire or Sudan species (Zaire PsV and Sudan PsV, respectively). We found that 3-hydroxyphthalic anhydride-modified human serum albumin (HP-HSA) was the most effective in inhibiting the entry of both Zaire PsV and Sudan PsV, with the 50% effective concentration being at the nanomolar level and with HP-HSA being more potent than EBOV-neutralizing antibody MIL77-2 (4G7, a component antibody of the ZMapp drug cocktail). The combination of HP-HSA and MIL77-2 exhibited a synergistic effect. HP-HSA had no obvious in vitro or in vivo toxicity. The EBOV PsV entry-inhibitory activity of HP-HSA remained intact after storage at 45°C for 8 weeks, suggesting that HP-HSA has the potential for worldwide use, including tropical regions in African countries, as either a therapeutic to treat EBOV infection or a prophylactic microbicide to prevent the sexual transmission of EBOV.

Nature Communications1区 · 综合性期刊

Prior vaccination with rVSV-ZEBOV does not interfere with but improves efficacy of postexposure antibody treatment

1区 · 综合性期刊

ArticleOA

作者: Prasad, Abhishek N ; Agans, Krystle N ; Zeitlin, Larry ; Geisbert, Thomas W ; Melody, Kevin ; Deer, Daniel J ; Feldmann, Heinz ; Fenton, Karla A ; Sprecher, Armand ; Borisevich, Viktoriya ; Bornholdt, Zachary A ; Geisbert, Joan B ; Cross, Robert W

AbstractA replication-competent vesicular stomatitis virus vaccine expressing the Ebola virus (EBOV) glycoprotein (GP) (rVSV-ZEBOV) was successfully used during the 2013-16 EBOV epidemic. Additionally, chimeric and human monoclonal antibodies (mAb) against the EBOV GP have shown promise in animals and humans when administered therapeutically. Uncertainty exists regarding the efficacy of postexposure antibody treatments in the event of a known exposure of a recent rVSV-ZEBOV vaccinee. Here, we model a worst-case scenario using rhesus monkeys vaccinated or unvaccinated with the rVSV-ZEBOV vaccine. We demonstrate that animals challenged with a uniformly lethal dose of EBOV one day following vaccination, and then treated with the anti-EBOV GP mAb MIL77 starting 3 days postexposure show no evidence of clinical illness and survive challenge. In contrast, animals receiving only vaccination or only mAb-based therapy become ill, with decreased survival compared to animals vaccinated and subsequently treated with MIL77. These results suggest that rVSV-ZEBOV augments immunotherapy.

Scientific Reports3区 · 综合性期刊

Treatment with hyperimmune equine immunoglobulin or immunoglobulin fragments completely protects rodents from Ebola virus infection

3区 · 综合性期刊

ArticleOA

作者: Gai, Weiwei ; Zheng, Ying ; Wong, Gary ; Li, Yuetao ; Yan, Feihu ; Wang, Tiecheng ; Chi, Hang ; Yang, Songtao ; Gao, Yuwei ; Huang, Geng ; Wang, Chong ; Cao, Zengguo ; Xia, Xianzhu ; Qian, Jun ; He, Shihua ; Fan, Quanshui ; Kobinger, Gary ; Wang, Hualei ; Zou, Yong ; Li, Nan ; Jin, Hongli ; Gao, George Fu ; Feng, Na ; Chen, Weijin ; Zhao, Yongkun ; Qiu, Xiangguo ; Zheng, Xuexing ; Chu, Di ; Bi, Yuhai

AbstractRecent successes with monoclonal antibody cocktails ZMappTM and MIL77 against Ebola virus (EBOV) infections have reignited interest in antibody-based therapeutics. Since the production process for monoclonal antibodies can be prolonged and costly, alternative treatments should be investigated. We produced purified equine antisera from horses hyperimmunized with EBOV virus-like particles, and tested the post-exposure efficacy of the antisera in a mouse model of infection. BALB/c mice were given up to 2 mg of purified equine antisera per animal, at 30 minutes, 1 or 2 days post-infection (dpi), in which all animals survived. To decrease the possibility of serum sickness, the equine antisera was digested with pepsin to generate F(ab′)2 fragments, with in vitro neutralizing activity comparable to whole immunoglobulin. Full protection was achieved with when treatment was initiated at 1 dpi, but the suboptimal protection observed with the 30 minute and 2 dpi groups demonstrate that in addition to virus neutralization, other Fc-dependent antibody mechanisms may also contribute to survival. Guinea pigs given 20 mg of antisera or F(ab′)2 at or starting at 1 or 2 dpi were also fully protected from EBOV infection. These results justify future efficacy studies for purified equine products in NHPs.

100 项与重组抗埃博拉病毒单克隆抗体联合(Mapp Biopharmaceutical, Inc.) 相关的药物交易

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适应症	最高研发状态	国家/地区	公司	日期
埃博拉病毒性疾病	临床1期	中国	北京天广实生物技术股份有限公司	2019-11-22
埃博拉病毒性疾病	临床1期	中国	中国人民解放军军事医学科学院	2019-11-22
埃博拉病毒性疾病	临床1期	中国	浙江海正药业股份有限公司	2019-11-22