{"doi":"10.17615/wfcd-xw35","title":"Prefusion-stabilized SARS-CoV-2 S2-only antigen provides protection against SARS-CoV-2 challenge","abstract":"Ever-evolving SARS-CoV-2 variants of concern (VOCs) have diminished the effectiveness of therapeutic antibodies and vaccines. Developing a coronavirus vaccine that offers a greater breadth of protection against current and future VOCs would eliminate the need to reformulate COVID-19 vaccines. Here, we rationally engineer the sequence-conserved S2 subunit of the SARS-CoV-2 spike protein and characterize the resulting S2-only antigens. Structural studies demonstrate that the introduction of interprotomer disulfide bonds can lock S2 in prefusion trimers, although the apex samples a continuum of conformations between open and closed states. Immunization with prefusion-stabilized S2 constructs elicits broadly neutralizing responses against several sarbecoviruses and protects female BALB/c mice from mouse-adapted SARS-CoV-2 lethal challenge and partially protects female BALB/c mice from mouse-adapted SARS-CoV lethal challenge. These engineering and immunogenicity results should inform the development of next-generation pan-coronavirus therapeutics and vaccines.","journal":"UNC Libraries","year":2024,"id":498966,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9568,"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":1193608,"name":"Leist S.R","orcid":null,"position":1,"is_corresponding":false},{"id":1346606,"name":"Jangra R.K.","orcid":null,"position":2,"is_corresponding":false},{"id":1117255,"name":"Ling Zhou","orcid":"0000-0003-3402-5719","position":3,"is_corresponding":false},{"id":1346607,"name":"Miller E.H.","orcid":null,"position":4,"is_corresponding":false},{"id":105602,"name":"Ande West","orcid":"0000-0001-7381-9533","position":5,"is_corresponding":false},{"id":1345994,"name":"K. Narayana Chandran","orcid":"0000-0002-8878-772X","position":6,"is_corresponding":false},{"id":1185287,"name":"Baric R.S","orcid":null,"position":7,"is_corresponding":false},{"id":1198178,"name":"Schisler J.C.","orcid":null,"position":8,"is_corresponding":false},{"id":611660,"name":"A. Wang","orcid":null,"position":9,"is_corresponding":false},{"id":1195248,"name":"McLellan J.S.","orcid":null,"position":10,"is_corresponding":false},{"id":1185187,"name":"Powers J.M.","orcid":null,"position":11,"is_corresponding":false},{"id":1346608,"name":"Zweigart M.R.","orcid":null,"position":12,"is_corresponding":false},{"id":1346609,"name":"Tse A.L.","orcid":null,"position":13,"is_corresponding":false},{"id":1346605,"name":"Hsieh C.-L.","orcid":null,"position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-19T02:09:45.971055Z","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":[]}