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Influenza: Striking differences in the response to immunisation in early childhood

Adjuvanted trivalent influenza vaccine: a randomised controlled trial to determine the kinetics of the functional genomic response in young children.

In the 2012 influenza season, ADITEC partners (University of Geneva, University of Oxford, Emory University Atlanta and Novartis) conducted a randomised controlled trial to assess the kinetics of the functional genomic response to adjuvanted trivalent influenza vaccine (TIV) in comparison with standard seasonal TIV and correlated with immunophenotypical data. Two doses of vaccine were administered one month apart. There were questions over the feasibility of using the systems immunology approach to vaccine assessment in young children (14-24 months in this trial) since only small volumes of blood (6mls) could be obtained for the study. Ninety children were enrolled and blood sampled at day 0, 1, 3 and 28 after the second dose of vaccine. To limit the number of blood samples per child, 2 groups were enrolled with an individual child allocated either to day 1 or day 3 sampling. Remarkably samples were obtained for gene expression studies (RNA), B and T cell EliSpots, flow cytometry and antibody measurement (using haemagglutination inhibition; HAI). Immunological analyses were undertaken in Oxford and HAI in Italy with microarray data analysed at Emory.

The majority of children were influenza naïve, since the previous season had a very low attack rate in the UK, and the majority were antibody and T cell response negative at baseline. Both vaccines were well tolerated. After vaccination, B cell, T cell, antibody and gene expression responses could be detected in the peripheral blood of the children and will be reported in a manuscript which is currently in preparation.
Comparison with previous adult studies of influenza vaccines indicate that there are striking differences in the response to immunisation in early childhood. These findings warrant further investigation to direct new understanding of the developing immune system and require a study which is focussed on the timepoints identified in this first ADITEC  TIV study in young children.

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