The genes associated with trans-dominance of the influenza A cold-adapted live virus vaccine.

Segment 7 (M) of the cold-adapted live influenza A virus vaccine plays a primary role in the ability of this virus to interfere with the replication of wild-type influenza A viruses. This conclusion is based on several lines of evidence. Single gene reassortant viruses derived by crossing influenza A/Ann Arbor/6/60 (H2N2) cold-adapted donor virus with an epidemic wild-type strain, A/Korea/1/82 (H3N2), were tested for their ability to interfere with wild-type parental virus in the Madin-Darby line of canine kidney cells and embryonated eggs. It was apparent in both hosts that the single gene reassortant carrying segment 7 (M) derived from the cold-adapted virus was dominant over wild-type virus. Additional confirmation of the role of segment 7 (M) in trans-dominance of the cold-adapted vaccine virus was derived from the analysis of reassortants produced by mixed infection by a wild-type virus and its cold-adapted reassortant vaccine strain. After three serial passages, the virus yield contained a high proportion of reassortants carrying segment 7 (M) of the cold-adapted parental strain. When used in mixed infections, these reassortants were dominant over the replication of the parental wild-type virus.