Approaches in the Development of the Potentially Pandemic LAIV Candidates

Influenza causes a major burden of acute respiratory disease each year. In addition, influenza pandemics occur on a regular basis. Vaccination is the most effective method of preventing seasonal and pandemic influenza. Currently, there are three types of influenza vaccines on the market: killed (inactivated), live attenuated (LAIV), and recombinant influenza vaccines. LAIV has sparked renewed interest in recent years, owing to WHO’s recognition of its benefits in the event of a pandemic. Classic reassortment of wild type influenza virus with cold–adapted master donor virus (MDV) in embryonated chicken eggs (Ultravac, Russia) and reverse–genetics technique (FluMist, USA) are two alternative approaches to generate LAIV candidates currently available. Avian influenza viruses continue to pose a serious pandemic risk. A variety of killed and live pandemic vaccines have been produced around the world in response to this threat. The aim of this chapter is to compile information from the growth, preclinical, and clinical testing of potentially pandemic LAIVs based on the cold–adapted A/Leningrad/134/17/57 master donor virus backbone obtained through a routine reassortment procedure. The LAIV candidates mentioned in this chapter are reassortants of wild–type (WT) viruses with MDV genomic compositions of 6:2 and 7:1. (6 MDV genes: 2 WT genes or 7 MDV genes : 1 WT gene, respectively). Despite variations in the genome formula, LAIV candidates of the H5, H7, and H2 subtypes developed temperature sensitivity, cold–adaptation, and attenuation in various animal models. They were found to be safe and immunogenic in healthy adult volunteers in clinical trials. According to the data, 7:1 reassortants carrying the only HA gene of a potentially pandemic virus as well as the remaining seven MDV genes could be potential candidates for the pandemic LAIV.

Author (s) Details

Irina Kiseleva
Institute of Experimental Medicine, Saint Petersburg, Russia and Saint Petersburg State University, Saint Petersburg, Russia and Smorodintsev Research Institute of Influenza, St Petersburg, Russia.

Natalie Larionova
Institute of Experimental Medicine, Saint Petersburg, Russia.

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