{"doi":"10.1101/2025.11.28.691177","title":"Development of a Recombinant Single-Cycle Influenza Viral Vector as an Intranasal Vaccine against SARS-CoV-2 and SARS-like Betacoronaviruses","abstract":"The COVID-19 pandemic has demonstrated the detrimental potential of zoonotic coronavirus transmission to human populations. Effective vaccines capable of eliciting immunity to SARS-CoV-2 have been pivotal in mitigating the spread of the virus. In this study, we describe the generation of a non-replicating pseudotyped influenza A virus (S-FLU), where the native haemagglutinin (HA) sequence is replaced with the coding sequence of either a membrane-anchored form (TM) or secretory form (Sec) of the receptor-binding domain (RBD) of the ancestral SARS-CoV-2 Wuhan (S-RBD Wuhan). We showed that both S-RBD-TM and S-RBD-Sec viruses can be generated via reverse genetics and grown to high titre. Intranasal immunisation in mice with S-RBD-TM elicits robust serum binding and neutralisation activity against SARS-CoV-2, superior to S-RBD-Sec. Furthermore, we demonstrate that a heterologous prime-boost immunisation regime in mice with S-RBD-TM Wuhan and S-RBD-TM BM48-31 (a distant Clade 3 SARS-like betacoronavirus (sarbecovirus)) increases antibody breadth against mismatched sarbecoviruses compared to homologous prime-boost with S-RBD-TM Wuhan. These results suggest that S-RBD-TM is a promising intranasal vaccine candidate against SARS-CoV-2 and may offer potential as a broadly protective sarbecovirus vaccine.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":583815,"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":0.9557,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1496756,"name":"Diana Melnyk","orcid":null,"position":1,"is_corresponding":false},{"id":1161419,"name":"Madeeha Afzal","orcid":"0000-0001-8954-8934","position":2,"is_corresponding":false},{"id":555229,"name":"Lisa Schimanski","orcid":null,"position":3,"is_corresponding":false},{"id":16982,"name":"Alexander A. Cohen","orcid":"0000-0002-2818-656X","position":4,"is_corresponding":false},{"id":16970,"name":"Jennifer R. Keeffe","orcid":"0000-0002-5317-6398","position":5,"is_corresponding":false},{"id":17000,"name":"Pamela J. Björkman","orcid":"0000-0002-2277-3990","position":6,"is_corresponding":false},{"id":461247,"name":"William James","orcid":"0000-0002-2506-1198","position":7,"is_corresponding":false},{"id":461108,"name":"Alain Townsend","orcid":"0000-0002-3702-0107","position":8,"is_corresponding":false},{"id":554471,"name":"Tiong Kit Tan","orcid":"0000-0001-8746-8308","position":9,"is_corresponding":false},{"id":1496755,"name":"Jonathan Munro","orcid":null,"position":0,"is_corresponding":true}],"reference_count":71,"raw_metadata":null,"created_at":"2026-07-19T02:59:07.970345Z","pmid":"41383761","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":[]}