Evaluation of: Gaucher D, Therrien R, Kettaf N et al. Yellow fever vaccine induces integrated multilineage and polyfunctional immune responses. J. Exp. Med. 205(13), 3119-3131 (2008). Despite the successful development of vaccines that are able to elicit potent and protective immune responses, the majority of vaccines were developed empirically and the mechanistic events leading to protective immune responses are often poorly understood. This impedes the development of new prophylactic as well as therapeutic vaccines for infectious diseases and cancer. Gaucher et al. took advantage of the effective yellow fever vaccine 17D to prospectively identify key immunological responses elicited by the vaccine using functional genomics and flow cytometric analysis. The results of the study clearly indicate 'that the immune response to a strong vaccine is preceded by the coordinated induction of master transcription factors that lead to the development of a broad, polyfunctional and persistent immune response integrating all effector cells of the immune system'.