reparing Live Influenza Vaccines against Potential Pandemic Influenza Using Nonpathogenic Avian Influenza Viruses and Cold-Adapted Master Donor Strain

Abstract

As part of an influenza pandemic preparedness program, the WHO analyzes a range of potentially pandemic influenza viruses for appropriate vaccines development. Several vaccine candidates were prepared using classical genetic reassortment, with the coldadapted A/Leningrad/134/17/57(H2N2) (Len/17) master donor strain (MDS) which is licensed in the Russia for the live influenza vaccine (LAIV) strains type A production for adults and children. The nonpathogenic avian viruses of different subtypes were used for reassortant vaccine strains preparation. All vaccine candidates demonstrated a high reproductive capacity and cold-adapted (ca-) phenotype in chick embryos. In mice, the LAIV of H5N2, H7N3, and H9N2 subtypes provided protection against infection with distant influenza viruses. The immunogenicity and protective efficacy of H7N3 LAIV was also demonstrated in ferrets. The H5N2 and H7N3 vaccine candidates demonstrated the inability to reproduce in chickens, which confirms the safety of their use in areas with highly developed agriculture. When tested in clinical trials, vaccine strains of H5N2 and H7N3 subtypes induce the conversions of antibodies homologous and antigenically distant variants. The use of LAIV can be effective against highly pathogenic influenza viruses even in the case of in