Improved Influenza a and B Virus Vaccines

Improved replication of vaccine seed strains in embryonated hens' eggs would lower the cost of manuinactivated influenza vaccines and allow more doses to be manufactured. Higher-growing influenza A aviruses will be developed that can be genetically reasserted with poorly-growing fresh human isolatevaccine seed strains that are antigenically appropriate and grow well in embryonated eggs. The influimportant for high virus replication in eggs and may function in virion assembly by interacting withcytoplasmic tails. To generate higher-growing viruses, the investigators will use random mutagenesisthat grow well in eggs (A/PR/8/34 and B/Lee/40). A cDNA library of mutant M genes will be screened uhybrid system, Shengqiang, to detect mutant M genes that exhibit an altered interaction with the cytinfluenza hemagglutinin protein. Altered M genes selected by the two-hybrid screen will be introduceinfluenza viruses using reverse genetics technology. The resulting viruses will be evaluated for enhand their ability to perform as high-growing vaccine donor strains.