Mapp Biopharmaceutical, Inc., San Diego, CA, USA.
United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD, USA.
Cell Host Microbe. 2019 Jan 9;25(1):49-58.e5. doi: 10.1016/j.chom.2018.12.005.
Recent and ongoing outbreaks of Ebola virus disease (EVD) underscore the unpredictable nature of ebolavirus reemergence and the urgent need for antiviral treatments. Unfortunately, available experimental vaccines and immunotherapeutics are specific for a single member of the Ebolavirus genus, Ebola virus (EBOV), and ineffective against other ebolaviruses associated with EVD, including Sudan virus (SUDV) and Bundibugyo virus (BDBV). Here we show that MBP134, a pan-ebolavirus therapeutic comprising two broadly neutralizing human antibodies (bNAbs), affords unprecedented effectiveness and potency as a therapeutic countermeasure to antigenically diverse ebolaviruses. MBP134 could fully protect ferrets against lethal EBOV, SUDV, and BDBV infection, and a single 25-mg/kg dose was sufficient to protect NHPs against all three viruses. The development of MBP134 provides a successful model for the rapid discovery and translational advancement of immunotherapeutics targeting emerging infectious diseases.
最近和正在发生的埃博拉病毒病 (EVD) 爆发突显了埃博拉病毒重新出现的不可预测性质,以及对抗病毒治疗的迫切需求。不幸的是,现有的实验性疫苗和免疫疗法是针对埃博拉病毒属的单一成员埃博拉病毒 (EBOV) 特异性的,对与 EVD 相关的其他埃博拉病毒无效,包括苏丹病毒 (SUDV) 和本迪布焦病毒 (BDBV)。在这里,我们表明 MBP134 是一种泛埃博拉病毒治疗药物,包含两种广泛中和的人类抗体 (bNAb),作为一种对抗具有不同抗原性的埃博拉病毒的治疗对策具有前所未有的有效性和效力。MBP134 可以完全保护雪貂免受致死性 EBOV、SUDV 和 BDBV 感染,并且单次 25 毫克/千克剂量足以保护非人灵长类动物免受这三种病毒的感染。MBP134 的开发为针对新发传染病的免疫治疗的快速发现和转化提供了一个成功的范例。