METHOD FOR GENERATING INFLUENZA A VIRUSES BEARING ATTENUATING MUTATIONS IN INTERNAL PROTEIN GENES

摘要

A vaccine donor strain of influenza A virus is produced that is attenuated due to one or more mutations in an internal protein gene. The attenuating mutations are introduced into an internal protein gene and transcripts are transfected into cells infected with a helper virus capable of rescuing the gene encoded by the transfected nucleic acid. The helper virus is usually host range-restricted and incapable of growth on mammalian cells, whereas helper virus that incorporates the transfected gene can thereafter grow on mammalian cells. Vaccines can be produced by co-infecting cultured cells with the vaccine donor strain and a wild-type strain of influenza A. Attenuated reassortants containing the hemagglutinin and/or neuraminidase genes of the wild-type strain are then used as live influenza vaccines.