Decreased effectiveness of the influenza A(H1N1)pdm09 strain in live attenuated influenza vaccines: an observational bias or a technical challenge?

There are currently two types of approved influenza vaccines: inactivated or recombinant vaccines, and live attenuated vaccines. The live attenuated influenza vaccines (LAIV) constructed on a backbone of an A/Leningrad virus strain into which the seasonal haemagglutinin (HA) and neuraminidase (NA) selected for the vaccine were inserted by reassortment, were used in the former Soviet Union for over 50 years [1]. Since the early 2000s, a different attenuated virus strain based on the A/Ann Arbor strain, has been approved for vaccine manufacturing in the United States (US) and more recently in the European Union/European Economic Area (EU/EEA) [2,3]. The proposed advantages of the LAIV were that they had superior efficacy compared to inactivated vaccines in young children [4], they were programmatically more suited to immunisation of children [5] and improved cost-effectiveness could potentially be achieved with childhood LAIV programmes [5-7]. LAIV have also been shown to be of great use in pandemic response since the production yield (doses per egg) is much greater than for inactivated vaccines, and the time between production and release is shorter. In addition, the nasal route of delivery could facilitate rapid population-wide immunisation during pandemics.