Therapeutic Treatment of Nipah Virus Infection in Nonhuman Primates with a Neutralizing Human Monoclonal Antibody

NIH and Colleagues Successfully Treat Nipah Virus in Monkeys

NIH scientists and their colleagues have used a human antibody called m102.4 to treat 12 African green monkeys infected with Nipah virus. Nipah has been found in Malaysia, Singapore, Bangladesh, and India. The virus targets the lungs and brain and has a high fatality rate in people.

The research is a continuation of the group’s successful work on Hendra virus, another pathogen for which there are no available treatments for people.

See the research article published in Science Translational Medicine http://stm.sciencemag.org/content/6/242/242ra82.

Sci Transl Med 25 June 2014: 
Vol. 6, Issue 242, p. 242ra82 
Sci. Transl. Med. DOI: 10.1126/scitranslmed.3008929

• RESEARCH ARTICLE

INFECTIOUS DISEASE

Therapeutic Treatment of Nipah Virus Infection in Nonhuman Primates with a Neutralizing Human Monoclonal Antibody

1. Thomas W. Geisbert1,2,*,†, 
2. Chad E. Mire1,2,*, 
3. Joan B. Geisbert1,2, 
4. Yee-Peng Chan3, 
5. Krystle N. Agans1,2,
6. Friederike Feldmann4, 
7. Karla A. Fenton1,2, 
8. Zhongyu Zhu5, 
9. Dimiter S. Dimitrov5, 
10. Dana P. Scott4,
11. Katharine N. Bossart6, 
12. Heinz Feldmann7 and 
13. Christopher C. Broder3,†

+Author Affiliations

1. ¹Galveston National Laboratory, University of Texas Medical Branch, Galveston, TX 77550, USA.
2. ²Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77550, USA.
3. ³Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
4. ⁴Rocky Mountain Veterinary Branch, National Institutes of Health (NIH), Hamilton, MT 59840, USA.
5. ⁵Laboratory of Experimental Immunology, Cancer and Inflammation Program, National Cancer Institute, NIH, Frederick, MD 21702, USA.
6. ⁶Department of Pathology, University of Texas Medical Branch, Galveston, TX 77550, USA.
7. ⁷Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, NIH, Hamilton, MT 59840, USA.

+Author Notes

• ↵* These authors contributed equally to this work.

1. ↵†Corresponding author. E-mail: twgeisbe@utmb.edu (T.W.G.); christopher.broder@usuhs.edu (C.C.B.)

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.

• Copyright © 2014, American Association for the Advancement of Science

Citation: T. W. Geisbert, C. E. Mire, J. B. Geisbert, Y-P. Chan, K. N. Agans, F. Feldmann, K. A. Fenton, Z. Zhu, D. S. Dimitrov, D. P. Scott, K. N. Bossart, H. Feldmann, C. C. Broder, Therapeutic Treatment of Nipah Virus Infection in Nonhuman Primates with a Neutralizing Human Monoclonal Antibody. Sci. Transl. Med. 6, 242ra82 (2014).

Read the Full Text