Document Detail


Defining limits of treatment with humanized neutralizing monoclonal antibody for West Nile virus neurological infection in a hamster model.
MedLine Citation:
PMID:  17452485     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
A potent anti-West Nile virus (anti-WNV)-neutralizing humanized monoclonal antibody, hE16, was previously shown to improve the survival of WNV-infected hamsters when it was administered intraperitoneally (i.p.), even after the virus had infected neurons in the brain. In this study, we evaluated the therapeutic limit of hE16 for the treatment of WNV infection in hamsters by comparing single-dose peripheral (i.p.) therapy with direct administration into the pons through a convection-enhanced delivery (CED) system. At day 5 after infection, treatments with hE16 by the peripheral and the CED routes were equally effective at reducing morbidity and mortality. In contrast, at day 6 only the treatment by the CED route protected the hamsters from lethal infection. These experiments suggest that hE16 can directly control WNV infection in the central nervous system. In support of this, hE16 administered i.p. was detected in a time-dependent manner in the serum, cerebrospinal fluid (CSF), cerebral cortex, brain stem, and spinal cord in CSF. A linear relationship between the hE16 dose and the concentration in serum was observed, and maximal therapeutic activity occurred at doses of 0.32 mg/kg of body weight or higher, which produced serum hE16 concentrations of 1.3 microg/ml or higher. Overall, these data suggest that in hamsters hE16 can ameliorate neurological disease after significant viral replication has occurred, although there is a time window that limits therapeutic efficacy.
Authors:
John D Morrey; Venkatraman Siddharthan; Aaron L Olsen; Hong Wang; Justin G Julander; Jeffery O Hall; Hua Li; Jeffrey L Nordstrom; Scott Koenig; Syd Johnson; Michael S Diamond
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Publication Detail:
Type:  Evaluation Studies; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2007-04-23
Journal Detail:
Title:  Antimicrobial agents and chemotherapy     Volume:  51     ISSN:  0066-4804     ISO Abbreviation:  Antimicrob. Agents Chemother.     Publication Date:  2007 Jul 
Date Detail:
Created Date:  2007-08-08     Completed Date:  2007-10-30     Revised Date:  2013-06-06    
Medline Journal Info:
Nlm Unique ID:  0315061     Medline TA:  Antimicrob Agents Chemother     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2396-402     Citation Subset:  IM    
Affiliation:
Institute for Antiviral Research, Animal, Dairy, and Veterinary Sciences Department, Utah State University, 4700 Old Main Hill, Logan, UT 84322-4700, USA. jmorrey@cc.usu.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Antibodies, Monoclonal / administration & dosage*,  blood,  cerebrospinal fluid,  therapeutic use*
Antiviral Agents / therapeutic use
Cricetinae
Disease Models, Animal
Dose-Response Relationship, Drug
Drug Evaluation, Preclinical
Female
Humans
Mesocricetus
Random Allocation
Time Factors
Treatment Outcome
Viral Plaque Assay
West Nile Fever / drug therapy*,  immunology,  mortality
West Nile virus / immunology*
Grant Support
ID/Acronym/Agency:
1-U54 AI-06357/AI/NIAID NIH HHS; N01-AI-15435/AI/NIAID NIH HHS; U01-AI061373/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Antiviral Agents
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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