Development of a novel monoclonal antibody with reactivity to a wide range of Venezuelan equine encephalitis virus strains.
BACKGROUND
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.


RESULTS
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.


CONCLUSIONS
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.
O'Brien
Lyn M
LM
Biomedical Sciences Department, Defence Science and Technology Laboratory, Porton Down, Salisbury, Wiltshire, SP4 0JQ, UK. lmobrien@dstl.gov.uk
Underwood-Fowler
Cindy D
CD
Goodchild
Sarah A
SA
Phelps
Amanda L
AL
Phillpotts
Robert J
RJ
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000627:therapeutic use; D000914:Antibodies, Viral / Q000276:immunology* / Q000627:therapeutic use; D002460:Cell Line; D002522:Chlorocebus aethiops; D004666:Encephalitis Virus, Venezuelan Equine / Q000276:immunology*; D004685:Encephalomyelitis, Venezuelan Equine / Q000517:prevention & control; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D019151:Peptide Library
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D019151:Peptide Library