Self-assembling virus-like particles represent highly attractive tools for developing next-generation vaccines and protein therapeutics. We created ADDomer, an adenovirus-derived multimeric protein-based self-assembling nanoparticle scaffold engineered to facilitate plug-and-play display of multiple immunogenic epitopes from pathogens. We used cryo–electron microscopy at near-atomic resolution and implemented novel, cost-effective, high-performance cloud computing to reveal architectural features in unprecedented detail. We analyzed ADDomer interaction with components of the immune system and developed a promising first-in-kind ADDomer-based vaccine candidate to combat emerging Chikungunya infectious disease, exemplifying the potential of our approach. Self-assembling protein-based nanoparticles are highly attractive tools for a broad range of biomedical applications, including vaccine development and cancer therapy (1–4). Present in all kingdoms of life, they form supramolecular architectures with unique properties (4), including spontaneous self-organization from simple precursor protomers amenable to engineering. Moreover, the particle size is generally in the range of pathog...