Computer-aided discovery of vaccine targets has become a cornerstone of rational vaccine design. In this article, I discuss how Machine Learning (ML) can inform and guide key computational steps in rational vaccine design concerned with the identification of B and T cell epitopes and correlates of protection. I provide examples of ML models, as well as types of data and predictions for which they are built. I argue that interpretable ML has the potential to improve the identification of immunogens also as a tool for scientific discovery, by helping elucidate the molecular processes underlying vaccine-induced immune responses. I outline the limitations and challenges in terms of data availability and method development that need to be addressed to bridge the gap between advances in ML predictions and their translational application to vaccine design.