{"doi":"10.1016/j.ebiom.2022.104341","title":"Multivalent S2-based vaccines provide broad protection against SARS-CoV-2 variants of concern and pangolin coronaviruses","abstract":"BACKGROUND: The COVID-19 pandemic continues to cause morbidity and mortality worldwide. Most approved COVID-19 vaccines generate a neutralizing antibody response that primarily targets the highly variable receptor-binding domain (RBD) of the SARS-CoV-2 spike (S) protein. SARS-CoV-2 \"variants of concern\" have acquired mutations in this domain allowing them to evade vaccine-induced humoral immunity. Recent approaches to improve the breadth of protection beyond SARS-CoV-2 have required the use of mixtures of RBD antigens from different sarbecoviruses. It may therefore be beneficial to develop a vaccine in which the protective immune response targets a more conserved region of the S protein. METHODS: Here we have developed a vaccine based on the conserved S2 subunit of the S protein and optimized the adjuvant and immunization regimen in Syrian hamsters and BALB/c mice. We have characterized the efficacy of the vaccine against SARS-CoV-2 variants and other coronaviruses. FINDINGS: Immunization with S2-based constructs elicited a broadly cross-reactive IgG antibody response that recognized the spike proteins of not only SARS-CoV-2 variants, but also SARS-CoV-1, and the four endemic human coronaviruses. Importantly, immunization reduced virus titers in respiratory tissues in vaccinated animals challenged with SARS-CoV-2 variants B.1.351 (beta), B.1.617.2 (delta), and BA.1 (omicron) as well as a pangolin coronavirus. INTERPRETATION: These results suggest that S2-based constructs can elicit a broadly cross-reactive antibody response resulting in limited virus replication, thus providing a framework for designing vaccines that elicit broad protection against coronaviruses. FUNDING: NIH, Japan Agency for Medical Research and Development, Garry Betty/ V Foundation Chair Fund, and NSF.","journal":"EBioMedicine","year":2022,"id":237018,"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":64,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9571,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":858616,"name":"Steven J. Frey","orcid":"0000-0003-1863-694X","position":1,"is_corresponding":false},{"id":858617,"name":"Kathryn Loeffler","orcid":"0009-0005-4935-5819","position":2,"is_corresponding":false},{"id":107106,"name":"Makoto Kuroda","orcid":"0000-0002-0487-4405","position":3,"is_corresponding":false},{"id":616891,"name":"Tadashi Maemura","orcid":null,"position":4,"is_corresponding":false},{"id":640879,"name":"Tammy Armbrust","orcid":"0000-0002-0997-2434","position":5,"is_corresponding":false},{"id":281192,"name":"Jie Yang","orcid":"0000-0003-0256-5569","position":6,"is_corresponding":false},{"id":5947,"name":"Yixuan J. Hou","orcid":"0000-0002-8323-7243","position":7,"is_corresponding":false},{"id":5952,"name":"Ralph S. Baric","orcid":"0000-0001-6827-8701","position":8,"is_corresponding":false},{"id":420653,"name":"Elizabeth Wright","orcid":"0000-0003-0712-9475","position":9,"is_corresponding":false},{"id":107110,"name":"Yoshihiro Kawaoka","orcid":"0000-0001-5061-8296","position":10,"is_corresponding":false},{"id":305337,"name":"Ravi S. Kane","orcid":"0000-0003-3084-4098","position":11,"is_corresponding":false},{"id":107104,"name":"Peter Halfmann","orcid":"0000-0002-1648-1625","position":0,"is_corresponding":true}],"reference_count":72,"raw_metadata":null,"created_at":"2026-07-19T00:22:08.925400Z","pmid":"36375316","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":[]}