Special Pathogens program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Canada.
Research and Development, Emergent BioSolutions Canada, Winnipeg, Manitoba, Canada.
J Virol. 2024 Aug 20;98(8):e0124223. doi: 10.1128/jvi.01242-23. Epub 2024 Jul 16.
Sudan ebolavirus (SUDV) is a member of the genus (Family ) and has caused sporadic outbreaks of Ebola disease (EBOD), or more specifically Sudan virus disease (SVD), with high mortality rates in Africa. Current vaccines and therapies that have been developed for filoviruses are almost all specific for Ebola virus (EBOV; of the species ), and there is a current lack of therapeutics specific for SUDV. The recent SUDV outbreak in Uganda, which was distributed across multiple districts, including Kampala, a densely populated urban center, highlights the critical need for the development of novel SUDV-specific or pan-Ebola virus therapeutics. Previous work has characterized two monoclonal antibodies, FVM04 and CA45, which have neutralization capabilities against both EBOV and SUDV and have shown protective efficacy in animal challenge studies. Here, we expand upon this work, showing that treatment with a monoclonal antibody cocktail consisting of FVM04 and CA45 provides full protection against lethal SUDV infection in cynomolgus macaques. Studies that evaluate outcomes at late time points after infection, once clinical signs of illness are apparent, are vital for assessing the therapeutic efficacy of antibody therapeutics. We have shown that when treatment is initiated as late as 5 days after infection, with a second dose given on day 8, that treated groups showed few clinical signs or morbidity, with complete survival. This work provides further evidence that FVM04 and CA45 have strong therapeutic potential against SUDV and their development as a pan-Ebola virus therapeutic should be pursued.
There are currently no approved vaccines or therapeutics for Sudan virus, a filovirus which is highly related to Ebola virus and causes similar disease and outbreaks. In this study, a cocktail of two potent monoclonal antibodies that effectively neutralize Sudan virus was tested in a nonhuman primate model of Sudan virus disease. Treatment was highly effective, even when initiated as late as 5 days after infection, when clinical signs of infection were already evident. All treated animals showed complete recovery from infection, with little evidence of disease, while all animals that received a control treatment succumbed to infection within 8 days. The study further demonstrated the strong therapeutic potential of the antibody treatment and supported further development for use in Sudan virus outbreaks.
苏丹埃博拉病毒（SUDV）是属（科）的一个成员，已在非洲造成埃博拉病（EBOB）的零星爆发，或更具体地说是苏丹病毒病（SVD），死亡率很高。目前针对丝状病毒开发的疫苗和疗法几乎都是针对埃博拉病毒（EBOV；物种）的，而目前缺乏针对 SUDV 的疗法。最近在乌干达爆发的 SUDV 疫情分布在多个地区，包括人口稠密的城市中心坎帕拉，这凸显了开发新型 SUDV 特异性或泛埃博拉病毒疗法的迫切需要。以前的工作已经描述了两种单克隆抗体，FVM04 和 CA45，它们具有中和 EBOV 和 SUDV 的能力，并在动物挑战研究中显示出保护效力。在这里，我们扩展了这项工作，表明用由 FVM04 和 CA45 组成的单克隆抗体混合物治疗可完全防止食蟹猴致命的 SUDV 感染。评估感染后晚期时间点（一旦出现疾病临床症状）的结果的研究对于评估抗体疗法的治疗效果至关重要。我们已经表明，即使在感染后 5 天开始治疗，并在第 8 天给予第二剂治疗，接受治疗的组也表现出很少的临床症状或发病率，并且完全存活。这项工作进一步证明了 FVM04 和 CA45 对 SUDV 具有很强的治疗潜力，应将其开发为泛埃博拉病毒疗法。
目前尚无针对苏丹病毒的批准疫苗或疗法，苏丹病毒是一种丝状病毒，与埃博拉病毒高度相关，可引起类似的疾病和爆发。在这项研究中，测试了两种有效中和苏丹病毒的强效单克隆抗体混合物在苏丹病毒病的非人类灵长类动物模型中的效果。治疗非常有效，即使在感染后 5 天开始治疗，当感染的临床症状已经明显时也是如此。所有接受治疗的动物均从感染中完全恢复，几乎没有疾病迹象，而所有接受对照治疗的动物均在 8 天内死于感染。该研究进一步证明了抗体治疗的强大治疗潜力，并支持进一步开发用于苏丹病毒爆发。
