Federal State Budgetary Institution "National Research Centre for Epidemiology and Microbiology named after the Honorary Academician N. F. Gamaleya" of the Ministry of Health of the Russian Federation, Moscow, Russia.
Federal State Budgetary Institution "National Research Centre for Epidemiology and Microbiology named after the Honorary Academician N. F. Gamaleya" of the Ministry of Health of the Russian Federation, Moscow, Russia.
Antiviral Res. 2019 Dec;172:104617. doi: 10.1016/j.antiviral.2019.104617. Epub 2019 Oct 5.
Ebola fever is an acute highly contagious viral disease characterized by severe course, high mortality and development of hemorrhagic syndrome (tendency to skin hemorrhage and bleeding of mucous membranes). The mortality rate of the disease 60-90%. Nowadays, there are no licensed specific therapeutic agents for Ebola in the world. Monoclonal antibodies (MAbs) having viral neutralizing activity with high specificity to the GP protein of the Ebola virus are considered as candidate highly effective antiviral drugs. In our study, for the first time a panel of mouse monoclonal antibodies specifically binding to EBOV GP protein was obtained using recombinant human adenovirus 5 serotype, expressing GP protein (Ad5-GP). The virus-neutralizing capacities of antibodies were evaluated on the Ebola virus cell infection model, as well as recombinant vesicular stomatitis virus pseudotyped by GP Ebola virus protein (rVSV-GP) cell infection model. Based on the results of virus neutralization, two most promising clones were selected, the specific and protective capacities of which were determined. The study of the protection of selected individual antibody clones, as well as their combinations on the model of lethal infection of rhesus macaques with Ebola virus showed that intravenous administration of a mixture of antibodies in the amount of 50 mg/kg 24 h after infection leads to the survival of 100% of the animals, while individual clones of antibodies possess partial protection (0-30%). The results of the study suggest the important role of antibodies in controlling replication of the Ebola virus in vivo and show the possibility of using a mixture of antibodies specific to the GP to protect against lethal infection with the Ebola virus in the post-infected mode of administration.
埃博拉热是一种急性高传染性病毒性疾病，其特征为严重的病程、高死亡率和出血性综合征（皮肤出血和粘膜出血倾向）的发展。该疾病的死亡率为 60-90%。目前，世界上没有针对埃博拉的许可的特效治疗药物。具有针对埃博拉病毒 GP 蛋白的高特异性病毒中和活性的单克隆抗体（MAbs）被认为是候选高效抗病毒药物。在我们的研究中，首次使用表达 GP 蛋白的重组人 5 型腺病毒（Ad5-GP）获得了一组特异性结合埃博拉病毒 GP 蛋白的小鼠单克隆抗体。使用埃博拉病毒细胞感染模型和由 GP 埃博拉病毒蛋白假型化的重组水疱性口炎病毒（rVSV-GP）细胞感染模型评估了抗体的病毒中和能力。基于病毒中和的结果，选择了两个最有前途的克隆，确定了它们的特异性和保护性。研究了选定的单克隆抗体克隆及其组合在致命性感染恒河猴的埃博拉病毒模型中的保护作用，结果表明，在感染后 24 小时内静脉内给予 50mg/kg 量的抗体混合物可使 100%的动物存活，而单独的抗体克隆则具有部分保护作用（0-30%）。研究结果表明抗体在控制体内埃博拉病毒复制中的重要作用，并表明使用针对 GP 的特异性抗体混合物在感染后给药模式下预防致命性埃博拉病毒感染的可能性。
