Vaccine responses have classically been characterized by the impact that individual genes or cell types have on a phenotype. Prof. Bali Pulendran asks: “Why restrict ourselves to a reductionistic method? We should look at the expression of all genes during an immune response!” Dr. Pulendran’s pioneering work helped create a new field of research called systems vaccinology, which lies at the interface of immunology, genomics, and data science. Using an unbiased, data-driven approach, his group has begun systematically unravelling the complex mechanisms by which innate immunity regulates vaccine immune responses.