A combination of two human monoclonal antibodies cures symptomatic rabies.

A combination of two human monoclonal antibodies cures symptomatic rabies.
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DOI:
10.15252/emmm.202012628
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发表时间:
2020-11-06
影响因子:
11.1
通讯作者:
Bourhy H
Bourhy H
中科院分区:
医学1区
文献类型:
--
作者:
de Melo GD;Sonthonnax F;Lepousez G;Jouvion G;Minola A;Zatta F;Larrous F;Kergoat L;Mazo C;Moigneu C;Aiello R;Salomoni A;Brisebard E;De Benedictis P;Corti D;Bourhy H

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狂犬病是一种被忽视的疾病,由嗜神经溶血病毒引起,主要通过受感染狗的咬伤传播给人类。狂犬病可通过疫苗或适当的暴露后预防(PEP)加以预防,但每年仍造成约6万人死亡。出现临床症状后无法治愈,即使采用先进的支持性治疗,病死率也接近100%。在这里,我们报告了两种针对病毒包膜糖蛋白的强效中和人单克隆抗体的组合治疗有症状的狂犬病小鼠。治疗效果需要通过脑室内输注在外周和中枢神经系统同时给予抗体。治疗后,恢复的小鼠临床状态良好,病毒载量检测不到,脑炎症谱基本正常。我们的发现为基于抗体的狂犬病症状治疗方法的概念提供了前所未有的证据。狂犬病是一种狂犬病病毒侵入中枢神经系统并表现出临床症状后的必然致死性疾病。这项研究证明了人类单克隆抗体(mab)的混合物可以治愈狂犬病症状。
Rabies is a neglected disease caused by a neurotropic Lyssavirus, transmitted to humans predominantly by the bite of infected dogs. Rabies is preventable with vaccines or proper post‐exposure prophylaxis (PEP), but it still causes about 60,000 deaths every year. No cure exists after the onset of clinical signs, and the case‐fatality rate approaches 100% even with advanced supportive care. Here, we report that a combination of two potent neutralizing human monoclonal antibodies directed against the viral envelope glycoprotein cures symptomatic rabid mice. Treatment efficacy requires the concomitant administration of antibodies in the periphery and in the central nervous system through intracerebroventricular infusion. After such treatment, recovered mice presented good clinical condition, viral loads were undetectable, and the brain inflammatory profile was almost normal. Our findings provide the unprecedented proof of concept of an antibody‐based therapeutic approach for symptomatic rabies. Rabies is an invariably fatal disease after the rabies virus has invaded the central nervous system and clinical signs have been manifested. This study brings the proof‐of‐concept that a cocktail of human monoclonal antibodies (mAbs) can cure symptomatic rabies.
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