{"doi":"10.7554/elife.57659","title":"Tailored design of protein nanoparticle scaffolds for multivalent presentation of viral glycoprotein antigens","abstract":"Multivalent presentation of viral glycoproteins can substantially increase the elicitation of antigen-specific antibodies. 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 de novo 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.","journal":"eLife","year":2020,"id":50574,"datarank":3.40806983778611,"base_score":5.241747015059643,"endowment":5.241747015059643,"self_citation_contribution":0.7862620522589465,"citation_network_contribution":2.6218077855271633,"self_endowment_contribution":0.7862620522589465,"citer_contribution":2.6218077855271633,"corpus_percentile":null,"corpus_rank":null,"citation_count":188,"citer_count":122,"citers_with_citation_signal":109,"citers_with_endowment":109,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9486,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":230743,"name":"Aleksandar Antanasijevic","orcid":"0000-0001-9452-8954","position":1,"is_corresponding":false},{"id":249504,"name":"Jorge A. 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