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To enable a new generation of anti-viral vaccines, we designed self-assembling protein nanoparticles with geometries tailored to present the ectodomains of influenza, HIV, and RSV viral glycoprotein trimers. We first\n                    <jats:italic>de novo<\/jats:italic>\n                    designed trimers tailored for antigen fusion, featuring N-terminal helices positioned to match the C termini of the viral glycoproteins. Trimers that experimentally adopted their designed configurations were incorporated as components of tetrahedral, octahedral, and icosahedral nanoparticles, which were characterized by cryo-electron microscopy and assessed for their ability to present viral glycoproteins. Electron microscopy and antibody binding experiments demonstrated that the designed nanoparticles presented antigenically intact prefusion HIV-1 Env, influenza hemagglutinin, and RSV F trimers in the predicted geometries. This work demonstrates that antigen-displaying protein nanoparticles can be designed from scratch, and provides a systematic way to investigate the influence of antigen presentation geometry on the immune response to vaccination.\n                  <\/jats:p>","DOI":"10.7554\/elife.57659","type":"journal-article","created":{"date-parts":[[2020,8,3]],"date-time":"2020-08-03T20:00:28Z","timestamp":1596484828000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.57659","source":"Crossref","is-referenced-by-count":169,"title":["Tailored design of protein nanoparticle scaffolds for multivalent presentation of viral glycoprotein antigens"],"prefix":"10.7554","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9792-7149","authenticated-orcid":true,"given":"George","family":"Ueda","sequence":"first","affiliation":[{"name":"Department of Biochemistry, University of Washington, Seattle, United States"},{"name":"Institute for Protein Design, University of Washington, Seattle, United 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