{"doi":"10.1128/jvi.00521-24","title":"Trimerized S expressed by modified vaccinia virus Ankara (MVA) confers superior protection against lethal SARS-CoV-2 challenge in mice","abstract":"The reoccurrence of successive waves of SARS-CoV-2 variants suggests the exploration of more vaccine alternatives is imperative. Modified vaccinia virus Ankara (MVA) is a virus vector exhibiting excellent safety as well as efficacy for vaccine development. Here, a series of recombinant MVAs (rMVAs) expressing monomerized or trimerized S proteins from different SARS-CoV-2 variants are engineered. Trimerized S expressed from rMVAs is found predominantly as trimers on the surface of infected cells. Remarkably, immunization of mice with rMVAs demonstrates that S expressed in trimer elicits higher levels of binding IgG and IgA, as well as neutralizing antibodies for matched and mismatched S proteins than S in the monomer. In addition, trimerized S expressed by rMVA induces enhanced cytotoxic T-cell responses than S in the monomer. Importantly, the rMVA vaccines expressing trimerized S exhibit superior protection against a lethal SARS-CoV-2 challenge as the immunized animals all survive without displaying any pathological conditions. This study suggests that opting for trimerized S may represent a more effective approach and highlights that the MVA platform serves as an ideal foundation to continuously advance SARS-CoV-2 vaccine development. IMPORTANCE: MVA is a promising vaccine vector and has been approved as a vaccine for smallpox and mpox. Our analyses suggested that recombinant MVA expressing S in trimer (rMVA-ST) elicited robust cellular and humoral immunity and was more effective than MVA-S-monomer. Importantly, the rMVA-ST vaccine was able to stimulate decent cross-reactive neutralization against pseudoviruses packaged using S from different sublineages, including Wuhan, Delta, and Omicron. Remarkably, mice immunized with rMVA-ST were completely protected from a lethal challenge of SARS-CoV-2 without displaying any pathological conditions. Our results demonstrated that an MVA vectored vaccine expressing trimerized S is a promising vaccine candidate for SARS-CoV-2 and the strategy might be adapted for future vaccine development for coronaviruses.","journal":"Journal of Virology","year":2024,"id":448787,"datarank":0.26876392038420827,"base_score":1.791759469228055,"endowment":1.791759469228055,"self_citation_contribution":0.26876392038420827,"citation_network_contribution":0.0,"self_endowment_contribution":0.26876392038420827,"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":0.9568,"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":1268169,"name":"Zhenshan Wang","orcid":null,"position":1,"is_corresponding":false},{"id":1060791,"name":"Yarui Li","orcid":"0000-0001-9371-7622","position":2,"is_corresponding":false},{"id":1060789,"name":"Zihui Zhang","orcid":"0000-0002-4346-8960","position":3,"is_corresponding":false},{"id":1061211,"name":"Shuning Ren","orcid":null,"position":4,"is_corresponding":false},{"id":1267715,"name":"Jing Wang","orcid":"0000-0001-5105-7718","position":5,"is_corresponding":false},{"id":1060790,"name":"Shijie Xie","orcid":"0009-0008-4801-8273","position":6,"is_corresponding":false},{"id":1267716,"name":"Zhiyi Liao","orcid":"0000-0003-1998-9763","position":7,"is_corresponding":false},{"id":1267717,"name":"Baifen Song","orcid":"0009-0007-0153-0360","position":8,"is_corresponding":false},{"id":1060794,"name":"Wenxue Wu","orcid":"0000-0002-0230-1830","position":9,"is_corresponding":false},{"id":1267718,"name":"Feihu Yan","orcid":"0000-0002-2808-5486","position":10,"is_corresponding":false},{"id":331278,"name":"Chen Peng","orcid":"0000-0001-6141-8775","position":11,"is_corresponding":false},{"id":1060787,"name":"Junda Zhu","orcid":"0009-0000-3520-9259","position":0,"is_corresponding":true}],"reference_count":43,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:02:12.215092Z","pmid":"38874361","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":[]}