title: A neutralizing human monoclonal antibody protects against lethal disease in a new ferret model of acute nipah virus infection.
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 TCID(50) 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.
authors.affiliation: CSIRO Livestock Industries, Australian Animal Health Laboratory, Geelong, Victoria, Australia. kbossart@bu.edu
authors.forename: Katharine N
authors.initials: KN
authors.lastname: Bossart
authors.forename: Zhongyu
authors.initials: Z
authors.lastname: Zhu
authors.forename: Deborah
authors.initials: D
authors.lastname: Middleton
authors.forename: Jessica
authors.initials: J
authors.lastname: Klippel
authors.forename: Gary
authors.initials: G
authors.lastname: Crameri
authors.forename: John
authors.initials: J
authors.lastname: Bingham
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: McEachern
authors.forename: Diane
authors.initials: D
authors.lastname: Green
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Hancock
authors.forename: Yee-Peng
authors.initials: YP
authors.lastname: Chan
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Hickey
authors.forename: Dimiter S
authors.initials: DS
authors.lastname: Dimitrov
authors.forename: Lin-Fa
authors.initials: LF
authors.lastname: Wang
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Broder
mesh_terms: D000208:Acute Disease; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D057134:Antibodies, Neutralizing / Q000276:immunology / Q000627:therapeutic use; D004195:Disease Models, Animal; D005289:Ferrets; D006023:Glycoproteins / Q000276:immunology; D045464:Henipavirus Infections / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D006801:Humans; D007150:Immunohistochemistry; D045405:Nipah Virus / Q000276:immunology / Q000472:pathogenicity*; D012367:RNA, Viral / Q000378:metabolism; D014018:Tissue Distribution; D014759:Viral Envelope Proteins / Q000276:immunology; D019562:Viral Load
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D006023:Glycoproteins; D012367:RNA, Viral; D014759:Viral Envelope Proteins