Infectious DNA as a vaccine against West Nile and other
flaviviruses
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, which is composed of cDNA of the West
Nile virus type 2 genome placed under transcriptional control
of an eukaryotic promoter and insterted into a derivative of
pBR322 plasmid, initiates 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 to initiate flavivirus
infection even when used in very small amounts.
Genetic material of West Nile virus type 2 (isolate 956D117B3)
has been used in the design of WN infectious DNA construct, from
which we have isolated a moleclulalry defined clonal variant
designated WN1415 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
substanitially attenuated 956D117B3 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 tyep 2 strain 956D117B3.
Although WN invectious DNA as a plasmid carrying the full falvivirus
genome controlled by eukaryotic transcription elements resembles
a DNA vaccine, it is 100- to 10,000-fold more efficient in inducing
antiviral protective immunity in mice via different inoculation
routes.
Patent: Pending
License: Negotiable
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