The subject invention pertains to attenuated influenza viruses, and related vaccines and methods, comprising a genetically modified viral genome. The genetically modified viral genome comprises a disruption in the non-structural (NS1) coding segment and one or more base substitution in the matrix membrane protein coding segment. The genetic modifications result in viruses that lose NS1 functionality, yet remain replication competent.本發明涉及減弱流感病毒,以及相關的疫苗和方法,其包含遺傳上修飾的病毒基因組。所述遺傳上修飾的病毒基因組包含非-結構(NS1)編碼段中的中斷和基質膜蛋白編碼段中的一個或多個堿基置換。所述遺傳修飾導致喪失NS1功能性但依然能夠複製的病毒。