A neutralizing human monoclonal antibody protects african green monkeys from hendra virus challenge.
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.
Department of Microbiology, Boston University School of Medicine, Boston, MA 02118, USA.
Katharine N
KN
Bossart
Thomas W
TW
Geisbert
Heinz
H
Feldmann
Zhongyu
Z
Zhu
Friederike
F
Feldmann
Joan B
JB
Geisbert
Lianying
L
Yan
Yan-Ru
YR
Feng
Doug
D
Brining
Dana
D
Scott
Yanping
Y
Wang
Antony S
AS
Dimitrov
Julie
J
Callison
Yee-Peng
YP
Chan
Andrew C
AC
Hickey
Dimiter S
DS
Dimitrov
Christopher C
CC
Broder
Barry
B
Rockx
D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics / Q000627:therapeutic use*; D057134:Antibodies, Neutralizing / Q000627:therapeutic use*; D002522:Chlorocebus aethiops; D045404:Hendra Virus / Q000472:pathogenicity*; D045464:Henipavirus Infections / Q000188:drug therapy* / Q000517:prevention & control; D006801:Humans
D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing