Identifying gnostic predictors of the vaccine response

► Gene-expression based predictors of response to vaccination have been developed and show promise in influenza and yellow-fever virus vaccines. ► Gene-expression based predictors often fail to provide mechanistic insight in the basis for vaccine response. ► New analytic and experimental tools now allow the function of individual genes in predictive signatures to be identified. ► Enriching predictive signatures with functional information about their constituent genes will make gene-expression based predictors more robust.