Nanostructures and nanostructure-based vaccines that display antigens capable of eliciting immune responses to infectious agents such as bacteria, viruses, and pathogens are provided. Some vaccines are useful for preventing or decreasing the severity of infection with an infectious agent, including, for example and without limitation, lyme disease, pertussis, herpes virus, orthomyxovirus, paramyxovirus, pneumovirus, filovirus, flavivirus, reovirus, retrovirus, meningococcus, or malaria. The antigens may be attached to the core of the nanostructure either non-covalently or covalently, including as a fusion protein or by other means. Multimeric antigens may optionally be displayed along a symmetry axis of the nanostructure. Also provided are proteins and nucleic acid molecules encoding such proteins, vaccine compositions, and methods of administration.