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

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. Cross; Thomas W. Geisbert; Karla A. Fenton; Larry Zeitlin

doi:10.1093/infdis/jiad278

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

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. Cross, Thomas W. GeisbertKarla A. Fenton, Larry Zeitlin

Microbiology And Immunology

Research output: Contribution to journal › Article › peer-review

1 Scopus citations

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.

Original language	English (US)
Pages (from-to)	S701-S711
Journal	Journal of Infectious Diseases
Volume	228
DOIs	https://doi.org/10.1093/infdis/jiad278
State	Published - Nov 15 2023

Keywords

Marburg virus
aerosol
antibody
monoclonal

ASJC Scopus subject areas

General Medicine

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10.1093/infdis/jiad278

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Abelson, D., Barajas, J., Stuart, L., Kim, D., Marimuthu, A., Hu, C., Yamamoto, B., Ailor, E., Whaley, K. J., Vu, H., Agans, K. N., Borisevich, V., Deer, D. J., Dobias, N. S., Woolsey, C., Prasad, A. N., Peel, J. E., Lawrence, W. S., Cross, R. W., ... Zeitlin, L. (2023). Long-term Prophylaxis Against Aerosolized Marburg Virus in Nonhuman Primates With an Afucosylated Monoclonal Antibody. Journal of Infectious Diseases, 228, S701-S711. https://doi.org/10.1093/infdis/jiad278

Abelson, D, Barajas, J, Stuart, L, Kim, D, Marimuthu, A, Hu, C, Yamamoto, B, Ailor, E, Whaley, KJ, Vu, H, Agans, KN, Borisevich, V, Deer, DJ, Dobias, NS, Woolsey, C, Prasad, AN, Peel, JE, Lawrence, WS , Cross, RW , Geisbert, TW, Fenton, KA & Zeitlin, L 2023, 'Long-term Prophylaxis Against Aerosolized Marburg Virus in Nonhuman Primates With an Afucosylated Monoclonal Antibody', Journal of Infectious Diseases, vol. 228, pp. S701-S711. https://doi.org/10.1093/infdis/jiad278

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

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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author = "Dafna Abelson and Jennifer Barajas and Lauren Stuart and Do Kim and Arumugapradeep Marimuthu and Chris Hu and Brent Yamamoto and Eric Ailor and Whaley, {Kevin J.} and Hong Vu and Agans, {Krystle N.} and Viktoriya Borisevich and Deer, {Daniel J.} and Dobias, {Natalie S.} and Courtney Woolsey and Prasad, {Abhishek N.} and Peel, {Jennifer E.} and Lawrence, {William S.} and Cross, {Robert W.} and Geisbert, {Thomas W.} and Fenton, {Karla A.} and Larry Zeitlin",

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AU - Abelson, Dafna

AU - Barajas, Jennifer

AU - Stuart, Lauren

AU - Kim, Do

AU - Marimuthu, Arumugapradeep

AU - Hu, Chris

AU - Yamamoto, Brent

AU - Ailor, Eric

AU - Whaley, Kevin J.

AU - Vu, Hong

AU - Agans, Krystle N.

AU - Borisevich, Viktoriya

AU - Deer, Daniel J.

AU - Dobias, Natalie S.

AU - Woolsey, Courtney

AU - Prasad, Abhishek N.

AU - Peel, Jennifer E.

AU - Lawrence, William S.

AU - Cross, Robert W.

AU - Geisbert, Thomas W.

AU - Fenton, Karla A.

AU - Zeitlin, Larry

PY - 2023/11/15

Y1 - 2023/11/15

N2 - 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.

AB - 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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KW - aerosol

KW - antibody

KW - monoclonal

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

Abstract

Keywords

ASJC Scopus subject areas

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