Systems biological approaches to measure and understand vaccine immunity in humans

•Recent studies have used systems biological approaches to predict vaccine efficacy.•Such studies are yielding new insights about the mechanisms underlying vaccine immunity.•Data acquisition, management and modeling represent major challenges.•Integration of multiple “omics” data also represents major challenges.•Overcoming such challenges will enable systems approaches to guide rational vaccine design.

Recent studies have demonstrated the utility of using systems approaches to identify molecular signatures that can be used to predict vaccine immunity in humans. Such approaches are now being used extensively in vaccinology, and are beginning to yield novel insights about the molecular networks driving vaccine immunity. In this review, we present a broad review of the methodologies involved in these studies, and discuss the promise and challenges involved in this emerging field of “systems vaccinology.”