A neutralizing human monoclonal antibody protects against lethal disease in a new ferret model of acute nipah virus infection.
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.
Bossart
Katharine N
KN
CSIRO Livestock Industries, Australian Animal Health Laboratory, Geelong, Victoria, Australia. kbossart@bu.edu
Zhu
Zhongyu
Z
Middleton
Deborah
D
Klippel
Jessica
J
Crameri
Gary
G
Bingham
John
J
McEachern
Jennifer A
JA
Green
Diane
D
Hancock
Timothy J
TJ
Chan
Yee-Peng
YP
Hickey
Andrew C
AC
Dimitrov
Dimiter S
DS
Wang
Lin-Fa
LF
Broder
Christopher C
CC
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
D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D006023:Glycoproteins; D012367:RNA, Viral; D014759:Viral Envelope Proteins