Document Detail


A neutralizing human monoclonal antibody protects african green monkeys from hendra virus challenge.
MedLine Citation:
PMID:  22013123     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Katharine N Bossart; Thomas W 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
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Science translational medicine     Volume:  3     ISSN:  1946-6242     ISO Abbreviation:  Sci Transl Med     Publication Date:  2011 Oct 
Date Detail:
Created Date:  2011-10-20     Completed Date:  2012-05-29     Revised Date:  2013-06-27    
Medline Journal Info:
Nlm Unique ID:  101505086     Medline TA:  Sci Transl Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  105ra103     Citation Subset:  IM    
Affiliation:
Department of Microbiology, Boston University School of Medicine, Boston, MA 02118, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antibodies, Monoclonal / pharmacokinetics,  therapeutic use*
Antibodies, Neutralizing / therapeutic use*
Cercopithecus aethiops
Hendra Virus / pathogenicity*
Henipavirus Infections / drug therapy*,  prevention & control
Humans
Grant Support
ID/Acronym/Agency:
AI054715/AI/NIAID NIH HHS; AI057159/AI/NIAID NIH HHS; AI077995/AI/NIAID NIH HHS; AI082121/AI/NIAID NIH HHS; N01-CO-12400/CO/NCI NIH HHS; R01 AI054715-05/AI/NIAID NIH HHS; U01 AI077995-04/AI/NIAID NIH HHS; U01 AI082121-01/AI/NIAID NIH HHS; U54 AI057159-06/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Antibodies, Neutralizing
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