title: Therapeutic treatment of Nipah virus infection in nonhuman primates with a neutralizing human monoclonal antibody.
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.
authors: Galveston National Laboratory, University of Texas Medical Branch, Galveston, TX 77550, USA. Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77550, USA. twgeisbe@utmb.edu christopher.broder@usuhs.edu.
authors: Thomas W
authors: TW
authors: Geisbert
authors: Galveston National Laboratory, University of Texas Medical Branch, Galveston, TX 77550, USA. Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77550, USA.
authors: Chad E
authors: CE
authors: Mire
authors: Galveston National Laboratory, University of Texas Medical Branch, Galveston, TX 77550, USA. Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77550, USA.
authors: Joan B
authors: JB
authors: Geisbert
authors: Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
authors: Yee-Peng
authors: YP
authors: Chan
authors: Galveston National Laboratory, University of Texas Medical Branch, Galveston, TX 77550, USA. Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77550, USA.
authors: Krystle N
authors: KN
authors: Agans
authors: Rocky Mountain Veterinary Branch, National Institutes of Health (NIH), Hamilton, MT 59840, USA.
authors: Friederike
authors: F
authors: Feldmann
authors: Galveston National Laboratory, University of Texas Medical Branch, Galveston, TX 77550, USA. Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77550, USA.
authors: Karla A
authors: KA
authors: Fenton
authors: Laboratory of Experimental Immunology, Cancer and Inflammation Program, National Cancer Institute, NIH, Frederick, MD 21702, USA.
authors: Zhongyu
authors: Z
authors: Zhu
authors: Laboratory of Experimental Immunology, Cancer and Inflammation Program, National Cancer Institute, NIH, Frederick, MD 21702, USA.
authors: Dimiter S
authors: DS
authors: Dimitrov
authors: Rocky Mountain Veterinary Branch, National Institutes of Health (NIH), Hamilton, MT 59840, USA.
authors: Dana P
authors: DP
authors: Scott
authors: Department of Pathology, University of Texas Medical Branch, Galveston, TX 77550, USA.
authors: Katharine N
authors: KN
authors: Bossart
authors: Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, NIH, Hamilton, MT 59840, USA.
authors: Heinz
authors: H
authors: Feldmann
authors: Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA. twgeisbe@utmb.edu christopher.broder@usuhs.edu.
authors: Christopher C
authors: CC
authors: Broder
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D057134:Antibodies, Neutralizing / Q000097:blood / Q000276:immunology*; D000914:Antibodies, Viral / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology; D002522:Chlorocebus aethiops / Q000276:immunology*; D045464:Henipavirus Infections / Q000276:immunology / Q000517:prevention & control* / Q000628:therapy* / Q000821:virology; D006801:Humans; D007150:Immunohistochemistry; D009500:Neutralization Tests; D045405:Nipah Virus / Q000276:immunology*; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000956:Antigens, Viral