{"doi":"10.1101/2022.03.13.484172","title":"Immunization with recombinant accessory protein-deficient SARS-CoV-2 protects against lethal challenge and viral transmission","abstract":"Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has led to a worldwide Coronavirus Disease 2019 (COVID-19) pandemic. Despite high efficacy of the authorized vaccines, protection against the surging variants of concern (VoC) was less robust. Live-attenuated vaccines (LAV) have been shown to elicit robust and long-term protection by induction of host innate and adaptive immune responses. We sought to develop a COVID-19 LAV by generating 3 double open reading frame (ORF)-deficient recombinant (r)SARS-CoV-2 simultaneously lacking two accessory open reading frame (ORF) proteins (ORF3a/ORF6, ORF3a/ORF7a, and ORF3a/ORF7b). Here, we report that these double ORF-deficient rSARS-CoV-2 have slower replication kinetics and reduced fitness in cultured cells as compared to their parental wild-type (WT) counterpart. Importantly, these double ORF-deficient rSARS-CoV-2 showed attenuation in both K18 hACE2 transgenic mice and golden Syrian hamsters. A single intranasal dose vaccination induced high levels of neutralizing antibodies against different SARS-CoV-2 VoC, and also activated viral component-specific T-cell responses. Notably, the double ORF-deficient rSARS-CoV-2 were able to protect, as determined by inhibition of viral replication, shedding, and transmission, against challenge with SARS-CoV-2. Collectively, our results demonstrate the feasibility to implement these double ORF-deficient rSARS-CoV-2 as safe, stable, immunogenic and protective LAV for the prevention of SARS-CoV-2 infection and associated COVID-19 disease.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":306376,"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":0.9529,"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":240057,"name":"Jun‐Gyu Park","orcid":"0000-0001-7163-3591","position":1,"is_corresponding":false},{"id":277648,"name":"Kevin Chiem","orcid":"0000-0002-3892-5944","position":2,"is_corresponding":false},{"id":651167,"name":"Piyush Dravid","orcid":"0000-0002-4790-9591","position":3,"is_corresponding":false},{"id":415937,"name":"Anna Allué‐Guardia","orcid":"0000-0002-1941-2545","position":4,"is_corresponding":false},{"id":245273,"name":"Andreu Garcia‐Vilanova","orcid":"0000-0002-2385-8718","position":5,"is_corresponding":false},{"id":510473,"name":"Amit Kapoor","orcid":"0000-0002-8117-7347","position":6,"is_corresponding":false},{"id":258415,"name":"Mark R. Walter","orcid":"0000-0003-2163-5550","position":7,"is_corresponding":false},{"id":432142,"name":"James J. Kobie","orcid":"0000-0001-8069-0272","position":8,"is_corresponding":false},{"id":228962,"name":"Richard K. Plemper","orcid":"0000-0003-2034-2107","position":9,"is_corresponding":false},{"id":245288,"name":"Jordi B. Torrelles","orcid":"0000-0001-7702-5941","position":10,"is_corresponding":false},{"id":2423,"name":"Luis Martínez‐Sobrido","orcid":"0000-0001-7084-0804","position":11,"is_corresponding":false},{"id":2361,"name":"Chengjin Ye","orcid":"0000-0002-1934-9494","position":0,"is_corresponding":true}],"reference_count":44,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:32:48.984902Z","pmid":"35313573","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":[]}