Therapeutic treatment of Nipah virus infection in nonhuman primates with a neutralizing human monoclonal antibody

Thomas W. Geisbert, Chad E. Mire, Joan B. Geisbert, Yee Peng Chan, Krystle N. Agans, Friederike Feldmann, Karla A. Fenton, Zhongyu Zhu, Dimiter S. Dimitrov, Dana P. Scott, Katharine N. Bossart, Heinz Feldmann, Christopher C. Broder

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58 Scopus citations

Abstract

Nipah virus (NiV) is an emerging zoonotic paramyxovirus that causes severe and often fatal disease in pigs and humans. There are currently no vaccines or treatments approved for human use. Studies in small-animal models of NiV infection suggest that antibody therapy may be a promising treatment. However, most studies have assessed treatment at times shortly after virus exposure before animals show signs of disease. We assessed the efficacy of a fully human monoclonal antibody, m102.4, at several time points after virus exposure including at the onset of clinical illness in a uniformly lethal nonhuman primate model of NiV disease. Sixteen African green monkeys (AGMs) were challenged intratracheally with a lethal dose of NiV, and 12 animals were infused twice with m102.4 (15 mg/kg) beginning at either 1, 3, or 5 days after virus challenge and again about 2 days later. The presence of viral RNA, infectious virus, and/or NiV-specific immune responses demonstrated that all subjects were infected after challenge. All 12 AGMs that received m102.4 survived infection, whereas the untreated control subjects succumbed to disease between days 8 and 10 after infection. AGMs in the day 5 treatment group exhibited clinical signs of disease, but all animals recovered by day 16. These results represent the successful therapeutic in vivo efficacy by an investigational drug against NiV in a nonhuman primate and highlight the potential impact that a monoclonal antibody can have on a highly pathogenic zoonotic human disease.

Original languageEnglish (US)
Article number242ra82
JournalScience Translational Medicine
Volume6
Issue number242
DOIs
StatePublished - Jun 25 2014

ASJC Scopus subject areas

  • Medicine(all)

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    Geisbert, T. W., Mire, C. E., Geisbert, J. B., Chan, Y. P., Agans, K. N., Feldmann, F., Fenton, K. A., Zhu, Z., Dimitrov, D. S., Scott, D. P., Bossart, K. N., Feldmann, H., & Broder, C. C. (2014). Therapeutic treatment of Nipah virus infection in nonhuman primates with a neutralizing human monoclonal antibody. Science Translational Medicine, 6(242), [242ra82]. https://doi.org/10.1126/scitranslmed.3008929