{"doi":"10.1101/2022.02.14.480460","title":"A live-attenuated SARS-CoV-2 vaccine candidate with accessory protein deletions","abstract":"We report a live-attenuated SARS-CoV-2 vaccine candidate with (i) re-engineered viral transcriptional regulator sequences and (ii) deleted open-reading-frames (ORF) 3, 6, 7, and 8 (Δ3678). The Δ3678 virus replicates about 7,500-fold lower than wild-type SARS-CoV-2 on primary human airway cultures, but restores its replication on interferon-deficient Vero-E6 cells that are approved for vaccine production. The Δ3678 virus is highly attenuated in both hamster and K18-hACE2 mouse models. A single-dose immunization of the Δ3678 virus protects hamsters from wild-type virus challenge and transmission. Among the deleted ORFs in the Δ3678 virus, ORF3a accounts for the most attenuation through antagonizing STAT1 phosphorylation during type-I interferon signaling. We also developed an mNeonGreen reporter Δ3678 virus for high-throughput neutralization and antiviral testing. Altogether, the results suggest that Δ3678 SARS-CoV-2 may serve as a live-attenuated vaccine candidate and a research tool for potential biosafety level-2 use.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":297483,"datarank":0.3453877639491069,"base_score":2.302585092994046,"endowment":2.302585092994046,"self_citation_contribution":0.3453877639491069,"citation_network_contribution":0.0,"self_endowment_contribution":0.3453877639491069,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9488,"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":105306,"name":"Xianwen Zhang","orcid":null,"position":1,"is_corresponding":false},{"id":614786,"name":"Jianying Liu","orcid":"0000-0001-7741-7339","position":2,"is_corresponding":false},{"id":105303,"name":"Hongjie Xia","orcid":"0000-0002-2520-7038","position":3,"is_corresponding":false},{"id":105308,"name":"Jing Zou","orcid":"0000-0002-8098-7284","position":4,"is_corresponding":false},{"id":105307,"name":"Antonio E. Muruato","orcid":null,"position":5,"is_corresponding":false},{"id":702538,"name":"Sivakumar Periasamy","orcid":"0000-0002-7038-5140","position":6,"is_corresponding":false},{"id":105300,"name":"Jessica A. Plante","orcid":"0000-0002-4768-7458","position":7,"is_corresponding":false},{"id":108476,"name":"Nathen E. Bopp","orcid":null,"position":8,"is_corresponding":false},{"id":805792,"name":"Chaitanya Kurhade","orcid":"0000-0002-6139-2461","position":9,"is_corresponding":false},{"id":235604,"name":"Alexander Bukreyev","orcid":"0000-0002-0342-4824","position":10,"is_corresponding":false},{"id":232720,"name":"Ping Ren","orcid":"0000-0002-4022-6667","position":11,"is_corresponding":false},{"id":985536,"name":"Tian Wang","orcid":"0000-0002-2376-9942","position":12,"is_corresponding":false},{"id":986074,"name":"Menachery Vineet D.","orcid":null,"position":13,"is_corresponding":false},{"id":105318,"name":"Kenneth S. Plante","orcid":"0000-0002-7485-3167","position":14,"is_corresponding":false},{"id":105317,"name":"Xuping Xie","orcid":"0000-0003-0918-016X","position":15,"is_corresponding":false},{"id":105319,"name":"Scott C. Weaver","orcid":"0000-0001-8016-8556","position":16,"is_corresponding":false},{"id":38215,"name":"Pei‐Yong Shi","orcid":"0000-0001-5553-1616","position":17,"is_corresponding":false},{"id":286061,"name":"Yang Liu","orcid":"0009-0001-4290-9170","position":0,"is_corresponding":true}],"reference_count":51,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:31:26.161109Z","pmid":"35194609","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":[]}