Flaviviruses are (+)RNA viruses that cause such diseases as West Nile fever/encephalitis, dengue fever, yellow fever, St. Louis encephalitis, Japanese encephalitis and tick-borne encephalitis. West Nile infectious DNA, can initiate the flavivirus infectious cycle directly after transfection into susceptible cells or after inoculation in animals in vivo by intramuscular needle or needle-free injection, or by intradermal biolistic delivery. Due to the stability of supercoiled DNA plasmid and high specific infectivity of the construct, West Nile infectious DNA is capable of initiating flavivirus infection even when used in very small amounts.

Genetic material of a West Nile virus has been used in the design of a WN infectious DNA construct, from which we have isolated a molecularly defined clonal variant that is significantly attenuated but remains highly immunogenic and protective in mice. Currently circulating in the US, West Nile strain WN NY99 represents a highly virulent WN type 1 virus. Immune responses developed upon infection with a substantially attenuated strain (whole virus) protects mice against challenge with 100 lethal doses of WN NY99. Similar protection is achieved upon immunization with infectious DNA consisting of the genome of West Nile virus type 2 strain 956D117B3.

Although the WN infectious DNA as a plasmid carrying the full flavivirus genome controlled by eukaryotic transcription elements resembles a DNA vaccine, it is 100-10,000-fold more efficient in inducing antiviral protective immunity in mice via different inoculation routes.

File Number: 2004 FY 08 

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