This work is devoted to the research of the live attenuated influenza vaccine (LAIV) comprising two reassortant B/USSR/60/69-based vaccine influenza viruses Victoria and Yamagata. The intranasal immunization of the CBA mice with both Victoria and Yamagata strains induced 100% lung protection against the subsequent infection with the wild-type influenza B viruses of any antigen lineage. The quadrivalent LAIV (qLAIV) comprising both reassortant influenza B viruses Victoria and Yamagata were safe and areactogenic in adult volunteers. Following qLAIV administration the immune response was achieved to both Victoria and Yamagata lineages.