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Development of a novel monoclonal antibody with reactivity to a wide range of Venezuelan equine encephalitis virus strains
Authors
A Krebber
AC Casamassima
+24 more
AJ Wright
AM Bennett
Amanda L Phelps
AR Hunt
Cindy D Underwood-Fowler
E Dubois
EJ Rayfield
H Ni
J Burmester
JH Mathews
KM Johnson
Lyn M O'Brien
MI Kirsch
PR Pittman
R Kontermann
RJ Phillpotts
RJ Phillpotts
RJ Phillpotts
Robert J Phillpotts
Sarah A Goodchild
SC Weaver
The Subcommitee on Arbovirus Laboratory Safety of the American Committee on Arthropod-borne Viruses
W Butcher
WA Marasco
Publication date
1 January 2009
Publisher
BioMed Central
Doi
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on
PubMed
Abstract
<p>Abstract</p> <p>Background</p> <p>There is currently a requirement for antiviral therapies capable of protecting against infection with Venezuelan equine encephalitis virus (VEEV), as a licensed vaccine is not available for general human use. Monoclonal antibodies are increasingly being developed as therapeutics and are potential treatments for VEEV as they have been shown to be protective in the mouse model of disease. However, to be truly effective, the antibody should recognise multiple strains of VEEV and broadly reactive monoclonal antibodies are rarely and only coincidentally isolated using classical hybridoma technology.</p> <p>Results</p> <p>In this work, methods were developed to reliably derive broadly reactive murine antibodies. A phage library was created that expressed single chain variable fragments (scFv) isolated from mice immunised with multiple strains of VEEV. A broadly reactive scFv was identified and incorporated into a murine IgG2a framework. This novel antibody retained the broad reactivity exhibited by the scFv but did not possess virus neutralising activity. However, the antibody was still able to protect mice against VEEV disease induced by strain TrD when administered 24 h prior to challenge.</p> <p>Conclusion</p> <p>A monoclonal antibody possessing reactivity to a wide range of VEEV strains may be of benefit as a generic antiviral therapy. However, humanisation of the murine antibody will be required before it can be tested in humans.</p> <p>Crown Copyright © 2009</p
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