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Introduction
Influenza is a life-threatening viral infection that may affect up to 40% of the world's population each year [1] . Vaccination remains the most effective means of preventing seasonal influenza epidemics, which are associated with significant morbidity and mortality worldwide.
Long-term observations have shown that live attenuated influenza vaccine (LAIV) has some major advantages over inactivated influenza vaccine (IIV). These advantages include ease of needle-free delivery, extremely low rate of adverse reactions, smaller infrastructure requirement for manufacturing, limited downstream processing and significantly higher yield in eggs (nearly 15 doses of LAIV can be produced from one embryonated egg). These factors make LAIV especially attractive for developing countries with a large population. Furthermore, the concept of replicating the vaccine virus in the nasal cavity and thus generating a specific immune response at the site of infection appears to be the most appropriate mode of immunization.
All these features of LAIV become even more relevant with the emergence of potentially pandemic influenza viruses of different serotypes. The World Health Organization (WHO) recognized the advantages of LAIV over IIV in the event of a pandemic and therefore included LAIV in its Global action plan for influenza vaccines [2,3] .
In Russia, LAIV has a long history of development, stage-wise improvement, licensing and use in public health. Since 1987, Russian LAIV has been used for the prophylaxis of influenza in children aged over three years, in adults and in the elderly. Currently, reassortant viruses for Russian LAIV are prepared by classical reassortment in eggs of wild-type influenza A and B viruses with two cold-adapted master donor viruses (MDVs) as a backbone: A/Leningrad/134/17/57 (H2N2) and B/USSR/60/69, respectively. Russian LAIV has been shown through studies to consistently provide superior effective protection, especially in children, compared to IIV.
The other LAIV used in the world, based on Ann-Arbor backbone has likewise been shown to provide superior protective efficacy in children, compared to IIV, through randomized controlled trials. Some recent studies have however suggested that since 2011 there has been a reduction in the comparative efficacy of the Ann-Arbor based LAIV compared to IIV. The cause is still unknown however efforts to understand this sudden loss of efficacy are focusing on the role of the A/California H1N1 component as well as the...