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Two monoclonal antibodies against glycoprotein Gn protect mice from Rift Valley Fever challenge by cooperative effects.
PLOS Neglected Tropical Diseases ( IF 3.8 ) Pub Date : 2020-03-11 , DOI: 10.1371/journal.pntd.0008143
Benjamin Gutjahr 1 , Markus Keller 1 , Melanie Rissmann 1 , Felicitas von Arnim 1 , Susanne Jäckel 1, 2 , Sven Reiche 3 , Reiner Ulrich 3, 4 , Martin H Groschup 1 , Martin Eiden 1
Affiliation  

Rift Valley fever virus (RVFV) is a zoonotic arbovirus that causes severe disease in humans and ruminants. The infection is characterized by abortions in pregnant animals, high mortality in neonates as well as febrile illness in humans that develop in 1% of cases encephalitis or hemorrhagic fever. There is presently no specific antiviral treatment for RVFV infection available. In this study, two monoclonal antibodies (mAbs), raised against glycoprotein Gn, were applied in a therapeutic study. Treatment of RVFV infected mice with neutralizing mAb Gn3 alone at two different time points (30 minutes before or 30 minutes after virus challenge) showed only moderate efficacy of about 58.3% survival in both applications. However, a combination therapy together with non-neutralizing mAb Gn32 demonstrated complete protection (100% survival) when applied 30 minutes after the lethal challenge dose. The increase of mAb efficacy is probably based on cooperative neutralization effects. These data suggest that a combination therapy with mAbs Gn3 and Gn32 could be an effective treatment option against RVFV infection.

中文翻译:

两种针对糖蛋白Gn的单克隆抗体通过协同作用保护小鼠免受裂谷热的攻击。

裂谷热病毒(RVFV)是一种人畜共患虫虫媒病毒,可导致人类和反刍动物的严重疾病。感染的特征是孕妇流产,新生儿死亡率高以及人类发烧性疾病,在1%的脑炎或出血热病例中会发生这种感染。目前尚无针对RVFV感染的特异性抗病毒治疗方法。在这项研究中,针对糖蛋白Gn的两种单克隆抗体(mAb)被用于治疗研究。在两个不同的时间点(病毒攻击前30分钟或攻击后30分钟)单独用中和mAb Gn3治疗RVFV感染的小鼠,在两种应用中仅显示约58.3%存活率的中等疗效。然而,在致死性攻击剂量后30分钟应用联合疗法与非中和性mAb Gn32一起可显示出完全的保护作用(100%存活)。mAb功效的提高可能是基于协同中和作用。这些数据表明,mAbs Gn3和Gn32的联合治疗可能是针对RVFV感染的有效治疗选择。
更新日期:2020-03-12
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