Influenza virus with mutant PB2 gene segment as live attenuated vaccines

摘要

A vaccine comprising an effective amount of a biologically isolated influenza virus, comprising: i) 8 different gene segments, including a PA viral gene segment, a PB1 viral gene segment, a mutant PB2 viral gene segment, a HA viral gene segment , an NA viral gene segment, an NP viral gene segment, an M viral gene segment (M1 and M2), and an NS viral gene segment (NS1 and NS2), ii) 8 different viral gene segments, including a PA viral gene segment , a PB1 viral gene segment, a mutant PB2 viral gene segment, a HA viral gene segment, an NA viral gene segment (NA and NB), an NP viral gene segment, an M (M1 and BM2) viral gene segment and a segment NS (NS1 and NS2) viral gene, or iii) 7 different gene segments, including a PA viral gene segment, a PB1 viral gene segment, a mutant PB2 viral gene segment, an HEF viral gene segment, an NP viral gene segment, a segment M (M1 and CM2) viral gene, and an NS (NS1 and NS2) viral gene segment; where the mutant PB2 viral gene segment includes 5 'and 3' PB2 non-coding and viral coding incorporation sequences flanking a heterologous nucleotide sequence, and does not include contiguous sequences corresponding to sequences encoding a functional PB2, where the heterologous nucleotide sequence is a gene that encodes a heterologous antigenic protein.