Approaches in the Development of the Potentially Pandemic LAIV Candidates

Each year, influenza causes a significant acute respiratory disease burden. In addition, influenza pandemics periodically occur. Vaccination is the best tool for the prevention of both seasonal and pandemic influenza. Currently, three different types of influenza vaccines are available on the market – killed (inactivated), live attenuated (LAIV) and recombinant. As of today, the interest in LAIV has increased, largely because WHO has recognized its advantages in the case of a pandemic situation. Two alternative approaches to generate LAIV candidates are currently existing – classical reassortment of wild type influenza virus with cold–adapted master donor virus (MDV) in embryonated chicken eggs (UltravacÒ, Russia) and reverse–genetics technique (FluMistÒ, the USA). Avian influenza viruses remain a major pandemic threat. In response to this threat, a number of killed and live pandemic vaccines have been developed worldwide. The objective of this chapter is to summarize data from the development and preclinical and clinical evaluations of potentially pandemic LAIVs on the cold–adapted A/Leningrad/134/17/57 master donor virus backbone obtained by routine reassortment procedure. The described in this chapter LAIV candidates are reassortants of wild–type (WT) virus with MDV of 6:2 and 7:1 genomic composition (6 MDV genes: 2 WT genes or 7 MDV genes : 1 WT gene, respectively). Despite the differences in this genome formula, LAIV candidates of H5, H7, and H2 subtypes acquired temperature sensitivity, cold–adaptation, and attenuation for different animal models. In clinical trials, they were safe and immunogenic for healthy adult volunteers. The collected data indicate that 7:1 reassortants carrying the only HA gene of potentially pandemic virus and the seven remaining genes from the MDV might be prospective candidates for the pandemic LAIV.