Association of vaccine handling conditions with effectiveness of live attenuated influenza vaccine against H1N1pdm09 viruses in the United States.

PURPOSE: This analysis examined potential causes of the lack of vaccine effectiveness (VE) of live attenuated influenza vaccine (LAIV) against A/H1N1pdm09 viruses in the United States (US) during the 2013-2014 season. Laboratory studies have demonstrated reduced thermal stability of A/California/07/2009, the A/H1N1pdm09 strain utilized in LAIV from 2009 through 2013-2014. METHODS: Post hoc analyses of a 2013-2014 test-negative case-control (TNCC) effectiveness study investigated associations between vaccine shipping conditions and LAIV lot effectiveness. Investigational sites provided the LAIV lot numbers administered to each LAIV recipient enrolled in the study, and the vaccine distributor used by the site for commercially purchased vaccine. Additionally, a review was conducted of 2009-2014 pediatric observational TNCC effectiveness studies of LAIV, summarizing effectiveness by type/subtype, season, and geographic location. RESULTS: From the 2013 to 2014 TNCC study, the proportion of LAIV recipients who tested positive for H1N1pdm09 was significantly higher among children who received a lot released between August 1 and September 15, 2013, compared with a lot shipped either earlier or later (21% versus 4%; P<0.01). A linear relationship was observed between the proportion of subjects testing positive for H1N1pdm09 and outdoor temperatures during truck unloading at distributors' central locations. The review of LAIV VE studies showed that in the 2010-2011 and 2013-2014 influenza seasons, no significant effectiveness of LAIV against H1N1pdm09 was demonstrated for the trivalent or quadrivalent formulations of LAIV in the US, respectively, in contrast to significant effectiveness against A/H3N2 and B strains during 2010-2014. CONCLUSIONS: This study showed that the lack of VE observed with LAIV in the US against H1N1pdm09 viruses was associated with exposure of some LAIV lots to temperatures above recommended storage conditions during US distribution, and is likely explained by the increased susceptibility of the A/California/7/2009 (H1N1pdm09) LAIV strain to thermal degradation. CLINICAL TRIAL REGISTRY: NCT01997450.