Exploring the limitations of peripheral blood transcriptional biomarkers in predicting influenza vaccine responsiveness

Systems biology has been recently applied to vaccinology to better understand immunological responses to the influenza vaccine. Particular attention has been paid to the identification of early signatures capable of predicting vaccine immunogenicity. Building fromprevious studies, we employed a recently established algorithm for signature-based clustering of expression profiles, SCUDO, to provide new insights into why blood-derived transcriptome biomarkers often fail to predict the seroresponse to the influenza virus vaccination. Specifically, preexisting immunity against one or more vaccine antigens, which was found to negatively affect the seroresponse, was identified as a confounding factor able to decouple early transcriptome fromlater antibody responses, resulting in the degradation of a biomarker predictive power. Finally, the broadly accepted definition of seroresponse to influenza virus vaccine, represented by the maximum response across the vaccine-targeted strains, was compared to a composite measure integrating the responses against all strains.This analysis revealed that compositemeasures provide amore accurate assessment of the seroresponse to multicomponent influenza vaccines.