The genetic diversity of pathogens presents a challenge to the development of broadly effective vaccines. In this issue, Scarselli et al. combine atomic-level structural information with genomics and classical vaccinology to design a single immunogen that elicits protective immunity against more than 300 natural variants of the bacterial pathogen meningococcus B. This accomplishment provides a glimpse of the power of structure-based vaccine design to create immunogens capable of eliciting protective responses against genetically diverse pathogens.