TopoBuilding precision vaccines To induce strong and targeted neutralizing antibody (nAb) responses against vaccine targets, one strategy has been to use computationally designed immunogens. However, the structural complexity of many known neutralization epitopes has posed a major challenge for the design of accurate epitope mimetics. Sesterhenn et al. created a protein design algorithm called TopoBuilder to design scaffolds for irregular and discontinuous neutralization epitopes. As a proof of principle, the authors generated epitope-focused immunogens based on the prefusion conformation of the respiratory syncytial virus (RSV) fusion protein. When these immunogens were used to vaccinate mice and nonhuman primates in RSV infection models, they generated targeted nAb responses to RSV and boosted site-specific nAb responses in heterologous prime-boost vaccination schemes. Science , this issue p. eaay5051