Predicting seasonal influenza vaccine response using systemic gene expression profiling

Seasonal influenza is a primary public health burden in the USA and globally. Annual vaccination programs are designed on the basis of circulating influenza viral strains. However, the effectiveness of the seasonal influenza vaccine is highly variable between seasons and among individuals. A number of factors are known to influence vaccination effectiveness including age, sex, and comorbidities. Here, we sought to determine whether whole blood gene expression profiling prior to vaccination is informative about pre-existing immunological status and the immunological response to vaccine. We performed whole transcriptome analysis using RNA sequencing (RNAseq) of whole blood samples obtained prior to vaccination from participants enrolled in an annual influenza vaccine trial. Serological status prior to vaccination and 28 days following vaccination were assessed using the hemagglutination inhibition assay (HAI) to define baseline immune status and the response to vaccination. We find evidence that genes with immunological functions are increased in expression in individuals with higher pre-existing immunity and in those individuals who mount a greater response to vaccination. Using a random forest model we find that this set of genes can be used to predict vaccine response with a performance similar to a model that incorporates physiological and prior vaccination status alone. Our study shows that increased expression of immunological genes, possibly reflecting greater plasmablast cell populations, prior to vaccination is associated with an enhanced response to vaccine. Furthermore, in the absence of demographic and physiological information gene expression signatures are informative about the likely response of an individual to seasonal influenza vaccination. Overall design: Comparative gene expression profiling of humans prior to influenza vaccination