{"doi":"10.1101/2024.07.01.601243","title":"A stabilized MERS-CoV spike ferritin nanoparticle vaccine elicits robust and protective neutralizing antibody responses","abstract":"Summary Middle East respiratory syndrome coronavirus (MERS-CoV) was first identified as a human pathogen in 2012 and causes ongoing sporadic infections and outbreak clusters. Despite case fatality rates (CFRs) of over 30% and the pandemic potential associated with betacoronaviruses, a safe and efficacious vaccine has not been developed for prevention of MERS in at-risk individuals. Here we report the design, in vitro characterization, and preclinical evaluation of MERS-CoV antigens. Our lead candidate comprises a stabilized spike ectodomain displayed on a self-assembling ferritin nanoparticle that can be produced from a high-expressing, stable cell pool. This vaccine elicits robust antibody titers in BALB/c mice as measured by MERS- CoV pseudovirus and live-virus neutralization assays. Immunization of non-human primates (NHPs) with a single dose of Alhydrogel-adjuvanted vaccine elicits >10 3 geometric mean titer (GMT) of pseudovirus neutralizing antibodies that can be boosted with a second dose. These antibody levels are durable, with GMTs that surpass the post-prime levels for more than 5 months post-boost. Importantly, sera from these NHPs exhibit broad cross-reactivity against lentiviruses pseudotyped with spike proteins from MERS-CoV clades A, B, and C as well as a more distant pangolin merbecovirus. In transgenic mice expressing human DPP4, immunization provided dose-dependent protection against MERS-CoV lethal challenge, and in an established alpaca challenge model, immunization fully protected against MERS-CoV infection. This protein-based MERS-CoV nanoparticle vaccine is a promising candidate for advancement to clinical development to protect at-risk individuals and for future use in a potential outbreak setting.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":485618,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9556,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1329125,"name":"Hannah Caruso","orcid":null,"position":1,"is_corresponding":false},{"id":1041386,"name":"Soyoon Park","orcid":"0000-0002-7399-411X","position":2,"is_corresponding":false},{"id":240901,"name":"Jui‐Lin Chen","orcid":"0000-0002-7646-4907","position":3,"is_corresponding":false},{"id":1328614,"name":"Jessica O’Rear","orcid":"0009-0008-6533-469X","position":4,"is_corresponding":false},{"id":1147562,"name":"Brian Ferrer","orcid":"0000-0003-0500-146X","position":5,"is_corresponding":false},{"id":783464,"name":"David M. Belnap","orcid":"0000-0002-0619-7487","position":6,"is_corresponding":false},{"id":1328615,"name":"Audrey Walker","orcid":"0000-0002-9181-0660","position":7,"is_corresponding":false},{"id":1329126,"name":"Anneliese Bruening","orcid":null,"position":8,"is_corresponding":false},{"id":228128,"name":"Airn E. Hartwig","orcid":"0000-0003-4830-8074","position":9,"is_corresponding":false},{"id":311355,"name":"Vida Ahyong","orcid":"0000-0002-8632-9629","position":10,"is_corresponding":false},{"id":1329127,"name":"Cristy S. Dougherty","orcid":null,"position":11,"is_corresponding":false},{"id":228136,"name":"Richard A. Bowen","orcid":"0000-0002-7576-2881","position":12,"is_corresponding":false},{"id":218090,"name":"Julie E. Ledgerwood","orcid":"0000-0002-2047-6052","position":13,"is_corresponding":false},{"id":574402,"name":"Michael S. Kay","orcid":"0000-0003-3186-9684","position":14,"is_corresponding":false},{"id":552689,"name":"Payton A. Weidenbacher","orcid":"0000-0002-7692-0458","position":15,"is_corresponding":false},{"id":816276,"name":"Brad A. Palanski","orcid":"0000-0002-4049-4274","position":16,"is_corresponding":false},{"id":226826,"name":"Abigail E. Powell","orcid":"0000-0001-6408-9495","position":0,"is_corresponding":true}],"reference_count":84,"raw_metadata":null,"created_at":"2026-07-19T02:07:52.536246Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}