Potentially Pandemic Live Influenza Vaccines Based on Russian Master Donor Virus are Genetically Stable after Replication in Humans

Stability of attenuating mutations is an important premise for live attenuated influenza vaccine (LAIV). The presence of multiple mutations in internal gene segments of live attenuated viruses contributes to the stability of their genomes and consistent phenotypic properties. This study describes the evaluation of results of clinical isolates obtained in Phase I clinical trials of three Russian LAIVs against potentially pandemic influenza viruses which may cause serious and fatal disease in humans. As part of clinical trials, nasal swabs were tested for vaccine virus shedding, for temperature sensitivity and cold–adaptation and for nucleotide sequence. Vaccine viruses isolated from the vaccinated subjects were shown to retain phenotypic characteristics and attenuating mutations. These data suggest genetic stability of vaccine virus after replication in humans. In addition, no vaccine virus was detected in the placebo groups indicating the lack of person–to–person transmission.