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用去岩藻糖基化单克隆抗体对非人类灵长类动物进行雾化马尔堡病毒的长期预防。

Long-term Prophylaxis Against Aerosolized Marburg Virus in Nonhuman Primates With an Afucosylated Monoclonal Antibody.

机构信息

Mapp Biopharmaceutical, Inc, San Diego, California, USA.

Integrated Biotherapeutics, Rockville, Maryland, USA.

出版信息

J Infect Dis. 2023 Nov 13;228(Suppl 7):S701-S711. doi: 10.1093/infdis/jiad278.

Abstract

Marburg virus (MARV) causes a hemorrhagic fever disease in human and nonhuman primates with high levels of morbidity and mortality. Concerns about weaponization of aerosolized MARV have spurred the development of nonhuman primate (NHP) models of aerosol exposure. To address the potential threat of aerosol exposure, a monoclonal antibody that binds MARV glycoprotein was tested, MR186YTE, for its efficacy as a prophylactic. MR186YTE was administered intramuscularly to NHPs at 15 or 5 mg/kg 1 month prior to MARV aerosol challenge. Seventy-five percent (3/4) of the 15 mg/kg dose group and 50% (2/4) of the 5 mg/kg dose group survived. Serum analyses showed that the NHP dosed with 15 mg/kg that succumbed to infection developed an antidrug antibody response and therefore had no detectable MR186YTE at the time of challenge. These results suggest that intramuscular dosing of mAbs may be a clinically useful prophylaxis for MARV aerosol exposure.

摘要

马尔堡病毒(MARV)可引起人类和非人类灵长类动物的出血热疾病,发病率和死亡率都很高。人们对气溶胶形式的 MARV 武器化的担忧,促使开发了非人类灵长类动物(NHP)气溶胶暴露模型。为了应对气溶胶暴露的潜在威胁,研究人员测试了一种针对 MARV 糖蛋白的单克隆抗体 MR186YTE,作为一种预防性治疗的效果。在 MARV 气溶胶挑战前 1 个月,MR186YTE 通过肌肉注射以 15 或 5mg/kg 的剂量给 NHP 给药。15mg/kg 剂量组的 75%(3/4)和 5mg/kg 剂量组的 50%(2/4)存活。血清分析表明,感染后死亡的接受 15mg/kg 剂量的 NHP 产生了抗药物抗体反应,因此在挑战时没有检测到 MR186YTE。这些结果表明,肌内注射单克隆抗体可能是 MARV 气溶胶暴露的一种临床有用的预防措施。

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