A Neutralizing Human Monoclonal Antibody Protects against Lethal Disease in a New Ferret Model of Acute Nipah Virus Infection |
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Authors: | Katharine N Bossart Zhongyu Zhu Deborah Middleton Jessica Klippel Gary Crameri John Bingham Jennifer A McEachern Diane Green Timothy J Hancock Yee-Peng Chan Andrew C Hickey Dimiter S Dimitrov Lin-Fa Wang Christopher C Broder |
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Institution: | 1. CSIRO Livestock Industries, Australian Animal Health Laboratory, Geelong, Victoria, Australia.; 2. Protein Interactions Group, CCRNP, CCR, NCI-Frederick, NIH, Frederick, Maryland, United States of America.; 3. BRP, SAIC-Frederick, Inc., NCI-Frederick, Frederick, Maryland, United States of America.; 4. Department of Microbiology and Immunology, Uniformed Services University, Bethesda, Maryland, United States of America.;Mount Sinai School of Medicine, United States of America |
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Abstract: | Nipah virus is a broadly tropic and highly pathogenic zoonotic paramyxovirus in the genus Henipavirus whose natural reservoirs are several species of Pteropus fruit bats. Nipah virus has repeatedly caused outbreaks over the past decade associated with a severe and often fatal disease in humans and animals. Here, a new ferret model of Nipah virus pathogenesis is described where both respiratory and neurological disease are present in infected animals. Severe disease occurs with viral doses as low as 500 TCID50 within 6 to 10 days following infection. The underlying pathology seen in the ferret closely resembles that seen in Nipah virus infected humans, characterized as a widespread multisystemic vasculitis, with virus replicating in highly vascular tissues including lung, spleen and brain, with recoverable virus from a variety of tissues. Using this ferret model a cross-reactive neutralizing human monoclonal antibody, m102.4, targeting the henipavirus G glycoprotein was evaluated in vivo as a potential therapeutic agent. All ferrets that received m102.4 ten hours following a high dose oral-nasal Nipah virus challenge were protected from disease while all controls died. This study is the first successful post-exposure passive antibody therapy for Nipah virus using a human monoclonal antibody. |
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