{"doi":"10.1101/2020.06.11.147496","title":"A Platform Incorporating Trimeric Antigens into Self-Assembling Nanoparticles Reveals SARS-CoV-2-Spike Nanoparticles to Elicit Substantially Higher Neutralizing Responses than Spike Alone","abstract":"Abstract Antigens displayed on self-assembling nanoparticles can stimulate strong immune responses and have been playing an increasingly prominent role in structure-based vaccines. However, the development of such immunogens is often complicated by inefficiencies in their production. To alleviate this issue, we developed a plug-and-play platform using the spontaneous isopeptide-bond formation of the SpyTag:SpyCatcher system to display trimeric antigens on self-assembling nanoparticles, including the 60-subunit Aquifex aeolicus lumazine synthase (LuS) and the 24-subunit Helicobacter pylori ferritin. LuS and ferritin coupled to SpyTag expressed well in a mammalian expression system when an N- linked glycan was added to the nanoparticle surface. The respiratory syncytial virus fusion (F) glycoprotein trimer – stabilized in the prefusion conformation and fused with SpyCatcher – could be efficiently conjugated to LuS-SpyTag or ferritin-SpyTag, enabling multivalent display of F trimers with prefusion antigenicity. Similarly, F-glycoprotein trimers from human parainfluenza virus-type 3 and spike-glycoprotein trimers from SARS-CoV-2 could be displayed on LuS nanoparticles with decent yield and antigenicity. Notably, murine vaccination with the SARS-CoV-2 spike-LuS nanoparticles elicited ~25-fold higher neutralizing responses, weight-per-weight relative to spike alone. The versatile platform described here thus allows for multivalent plug-and-play presentation on self-assembling nanoparticles of trimeric viral antigens, with SARS-CoV-2 spike-LuS nanoparticles inducing particularly potent neutralizing responses.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":119718,"datarank":0.42498200160843247,"base_score":2.833213344056216,"endowment":2.833213344056216,"self_citation_contribution":0.42498200160843247,"citation_network_contribution":0.0,"self_endowment_contribution":0.42498200160843247,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":16,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9507,"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":266882,"name":"Cara W. 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Stewart-Jones","orcid":"0000-0002-2440-3790","position":9,"is_corresponding":false},{"id":266886,"name":"Raffaello Verardi","orcid":"0000-0002-2613-1223","position":10,"is_corresponding":false},{"id":105588,"name":"Lingshu Wang","orcid":"0000-0002-8404-4910","position":11,"is_corresponding":false},{"id":229157,"name":"Shuishu Wang","orcid":"0000-0002-0865-4522","position":12,"is_corresponding":false},{"id":266887,"name":"Anne P. Werner","orcid":"0000-0003-2322-6830","position":13,"is_corresponding":false},{"id":105601,"name":"Eun Sung Yang","orcid":"0000-0003-3161-1624","position":14,"is_corresponding":false},{"id":266888,"name":"Christina Yap","orcid":"0000-0002-6715-2514","position":15,"is_corresponding":false},{"id":105631,"name":"Tongqing Zhou","orcid":"0000-0002-3935-4637","position":16,"is_corresponding":false},{"id":105614,"name":"John R. Mascola","orcid":"0000-0002-5293-4695","position":17,"is_corresponding":false},{"id":266889,"name":"Nancy J. 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