Infectious disease

A neutralizing human monoclonal antibody protects African green monkeys from Hendra virus challenge

Katharine N. Bossart, Thomas Geisbert, Heinz Feldmann, Zhongyu Zhu, Friederike Feldmann, Joan B. Geisbert, Lianying Yan, Yan Ru Feng, Doug Brining, Dana Scott, Yanping Wang, Antony S. Dimitrov, Julie Callison, Yee Peng Chan, Andrew C. Hickey, Dimiter S. Dimitrov, Christopher C. Broder, Barry Rockx

Research output: Contribution to journalArticle

81 Citations (Scopus)

Abstract

Hendra virus (HeV) is a recently emerged zoonotic paramyxovirus that can cause a severe and often fatal disease in horses and humans. HeV is categorized as a biosafety level 4 agent, which has made the development of animal models and testing of potential therapeutics and vaccines challenging. Infection of African green monkeys (AGMs) with HeV was recently demonstrated, and disease mirrored fatal HeV infection in humans, manifesting as a multisystemic vasculitis with widespread virus replication in vascular tissues and severe pathologic manifestations in the lung, spleen, and brain. Here, we demonstrate that m102.4, a potent HeV-neutralizing human monoclonal antibody (hmAb), can protect AGMs from disease after infection with HeV. Fourteen AGMs were challenged intratracheally with a lethal dose of HeV, and 12 subjects were infused twice with a 100-mg dose of m102.4 beginning at either 10, 24, or 72 hours after infection and again about 48 hours later. The presence of viral RNA, infectious virus, and HeV-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 on day 8 after infection. Animals in the 72-hour treatment group exhibited neurological signs of disease, but all animals started to recover by day 16 after infection. These results represent successful post-exposure in vivo efficacy by an investigational drug against HeV and highlight the potential impact a hmAb can have on human disease.

Original languageEnglish (US)
Article number105ra103
JournalScience Translational Medicine
Volume3
Issue number105
DOIs
StatePublished - Oct 19 2011

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Hendra Virus
Cercopithecus aethiops
Communicable Diseases
Monoclonal Antibodies
Infection
Monkey Diseases
Horse Diseases
Investigational Drugs
Animal Diseases
RNA Viruses
Zoonoses
Viral RNA
Virus Diseases
Virus Replication
Vasculitis
Blood Vessels
Vaccines
Spleen
Animal Models

ASJC Scopus subject areas

  • Medicine(all)

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Infectious disease : A neutralizing human monoclonal antibody protects African green monkeys from Hendra virus challenge. / Bossart, Katharine N.; Geisbert, Thomas; Feldmann, Heinz; Zhu, Zhongyu; Feldmann, Friederike; Geisbert, Joan B.; Yan, Lianying; Feng, Yan Ru; Brining, Doug; Scott, Dana; Wang, Yanping; Dimitrov, Antony S.; Callison, Julie; Chan, Yee Peng; Hickey, Andrew C.; Dimitrov, Dimiter S.; Broder, Christopher C.; Rockx, Barry.

In: Science Translational Medicine, Vol. 3, No. 105, 105ra103, 19.10.2011.

Research output: Contribution to journalArticle

Bossart, KN, Geisbert, T, Feldmann, H, Zhu, Z, Feldmann, F, Geisbert, JB, Yan, L, Feng, YR, Brining, D, Scott, D, Wang, Y, Dimitrov, AS, Callison, J, Chan, YP, Hickey, AC, Dimitrov, DS, Broder, CC & Rockx, B 2011, 'Infectious disease: A neutralizing human monoclonal antibody protects African green monkeys from Hendra virus challenge', Science Translational Medicine, vol. 3, no. 105, 105ra103. https://doi.org/10.1126/scitranslmed.3002901
Bossart, Katharine N. ; Geisbert, Thomas ; Feldmann, Heinz ; Zhu, Zhongyu ; Feldmann, Friederike ; Geisbert, Joan B. ; Yan, Lianying ; Feng, Yan Ru ; Brining, Doug ; Scott, Dana ; Wang, Yanping ; Dimitrov, Antony S. ; Callison, Julie ; Chan, Yee Peng ; Hickey, Andrew C. ; Dimitrov, Dimiter S. ; Broder, Christopher C. ; Rockx, Barry. / Infectious disease : A neutralizing human monoclonal antibody protects African green monkeys from Hendra virus challenge. In: Science Translational Medicine. 2011 ; Vol. 3, No. 105.
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