Dengue viruses that are replication defective in mosquitos...

C - Chemistry – Metallurgy – 12 – N

Patent

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Details

C12N 7/01 (2006.01) A61K 39/12 (2006.01) C07K 14/18 (2006.01) C12N 7/04 (2006.01) C12N 15/40 (2006.01) C12N 15/86 (2006.01)

Patent

CA 2341354

The present invention is directed toward vector stage replication-defective flaviviruses that are replication-defective in mosquisto vectors that transmit them to human. Such mutant flaviviruses may be useful as vaccines. The replication-defective flaviviruses of the present invention demonstrate a limited ability to replicate in the vector organisms that transmit flaviviruses from one host to another. More specifically, the present invention is directed toward the construction and propagation of flaviviruses that possess 3'-noncoding regions altered in such a way as to prevent or severely limit viral reproduction in a vector organism. In one embodiment of the present invention, a replication-defective dengue virus that is replication-defective in arthropods is contemplated for use as a vaccine. In another embodiment, a replication-defective dengue virus that is replication-defective in mosquitos is contemplated for use as a vaccine. The present invention also contemplates methods of producing such mutant flaviviruses for use as vaccines as well as methods that induce a protective immunity against flavivirus infection or disease in an immunized subject.

La présente invention concerne des flavivirus possédant des défauts de réplication au stade vecteur chez les moustiques qui les transmettent aux humains. Ces flavivirus mutants peuvent servir de vaccins. Les flavivirus de la présente invention possédant des défauts de réplication manifestent une capacité de réplication limitée dans les organismes vecteurs qui transportent les flavivirus d'un hôte à l'autre. L'invention concerne plus particulièrement la construction et la propagation de flavivirus qui possèdent des régions non codantes 3' modifiées, et ce de manière à empêcher ou à limiter fortement la reproduction virale dans un organisme vecteur. Dans un mode de réalisation de la présente invention, on envisage d'utiliser comme vaccin un virus de la dengue qui possède des défauts de réplication chez les arthropodes. Dans un autre mode de réalisation, on envisage d'utiliser comme vaccin un virus de la dengue qui possède des défauts de réplication chez les moustiques. La présente invention concerne aussi des procédés pour produire ces flavivirus mutants afin de les utiliser comme vaccins ainsi que des procédés qui induisent une immunité protégeant contre une infection ou une maladie due aux flavivirus chez un sujet immunisé.

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