This article reviews the development of two attenuated West Nile virus (WNV
) variants, WNI-25 and WNI-25A. These variants have lost the neuroinvasion
trait of the parental virus. Attenuation was achieved through serial passag
es in mosquito cells and neutralization escape from WNV-specific monoclonal
antibody. Genetic analysis reveals amino acid changes between the parental
and each of the variants. The attenuated variants preserve the ability to
replicate in mice and geese and to induce a protective immune response. WNI
-25A was found to be a genetically stable virus. This variant was successfu
lly used as a live vaccine to protect geese against a wild-type virulent WN
V field isolate that closely resembles the WNV isolated during the 1999 New
York epidemic.