Efficacy of Human Monoclonal Antibody Monotherapy Against Bundibugyo Virus Infection in Nonhuman Primates

Pavlo Gilchuk, Chad Mire, Joan B. Geisbert, Krystle N. Agans, Daniel J. Deer, Robert Cross, James C. Slaughter, Andrew I. Flyak, Jeremy Mani, Michael H. Pauly, Jesus Velasco, Kevin J. Whaley, Larry Zeitlin, Thomas Geisbert, James E. Crowe

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Abstract

Background: The 2013-2016 Ebola virus disease (EVD) epidemics in West Africa highlighted a need for effective therapeutics for treatment of the disease caused by filoviruses. Monoclonal antibodies (mAbs) are promising therapeutic candidates for prophylaxis or treatment of virus infections. Data about efficacy of human mAb monotherapy against filovirus infections in preclinical nonhuman primate models are limited. Methods: Previously, we described a large panel of human mAbs derived from the circulating memory B cells from Bundibugyo virus (BDBV) infection survivors that bind to the surface glycoprotein (GP) of the virus. We tested one of these neutralizing mAbs that recognized the glycan cap of the GP, designated mAb BDBV289, as monotherapy in rhesus macaques. Results: We found that recombinant mAb BDBV289-N could confer up to 100% protection to BDBV-infected rhesus macaques when treatment was initiated as late as 8 days after virus challenge. Protection was associated with survival and decreased viremia levels in the blood of treated animals. Conclusions: These findings define the efficacy of monotherapy of lethal BDBV infection with a glycan cap-specific mAb and identify a candidate mAb therapeutic molecule that could be included in antibody cocktails for prevention or treatment of ebolavirus infections.

Original languageEnglish (US)
Pages (from-to)S565-S573
JournalThe Journal of infectious diseases
Volume218
Issue number5
DOIs
StatePublished - Nov 22 2018

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

Cite this

Gilchuk, P., Mire, C., Geisbert, J. B., Agans, K. N., Deer, D. J., Cross, R., Slaughter, J. C., Flyak, A. I., Mani, J., Pauly, M. H., Velasco, J., Whaley, K. J., Zeitlin, L., Geisbert, T., & Crowe, J. E. (2018). Efficacy of Human Monoclonal Antibody Monotherapy Against Bundibugyo Virus Infection in Nonhuman Primates. The Journal of infectious diseases, 218(5), S565-S573. https://doi.org/10.1093/infdis/jiy295