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

使用无岩藻糖基化单克隆抗体对非人类灵长类动物进行气雾化马尔堡病毒的长期预防

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作者:Dafna Abelson, Jennifer Barajas, Lauren Stuart, Do Kim, Arumugapradeep Marimuthu, Chris Hu, Brent Yamamoto, Eric Ailor, Kevin J Whaley, Hong Vu, Krystle N Agans, Viktoriya Borisevich, Daniel J Deer, Natalie S Dobias, Courtney Woolsey, Abhishek N Prasad, Jennifer E Peel, William S Lawrence, Robert W

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.

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