Structure-based immunogen design-leading the way to the new age of precision vaccines

Vaccines have been one of the most successful interventions in global health. However, traditional vaccine development has proven insufficient to deal with pathogens that elude the immune system through highly variable and non-functional epitopes. Emerging B cell technologies have yielded potent monoclonal antibodies targeting conserved epitopes, and their structural characterization has provided templates for rational immunogen design. Here, we review immunogen design strategies that leverage structural information to steer bulk immune responses towards the induction of precise antibody specificities targeting key antigenic sites. Immunogens designed to elicit well-defined antibody responses will become the basis of what we dubbed precision vaccines. Such immunogens have been used to tackle long-standing vaccine problems and have demonstrated their potential to seed the next-generation of vaccines.