DENGUE VIRUSES THAT ARE REPLICATION DEFECTIVE IN MOSQUITOS FOR USE AS VACCINES

摘要

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.