{"doi":"10.1371/journal.ppat.1012585","title":"Intranasal parainfluenza virus-vectored vaccine expressing SARS-CoV-2 spike protein of Delta or Omicron B.1.1.529 induces mucosal and systemic immunity and protects hamsters against homologous and heterologous challenge","abstract":"The continuous emergence of new SARS-CoV-2 variants requires that COVID vaccines be updated to match circulating strains. We generated B/HPIV3-vectored vaccines expressing 6P-stabilized S protein of the ancestral, B.1.617.2/Delta, or B.1.1.529/Omicron variants as pediatric vaccines for intranasal immunization against HPIV3 and SARS-CoV-2 and characterized these in hamsters. Following intranasal immunization, these B/HPIV3 vectors replicated in the upper and lower respiratory tract and induced mucosal and serum anti-S IgA and IgG. B/HPIV3 expressing ancestral or B.1.617.2/Delta-derived S-6P induced serum antibodies that effectively neutralized SARS-CoV-2 of the ancestral and B.1.617.2/Delta lineages, while the cross-neutralizing potency of B.1.1.529/Omicron S-induced antibodies was lower. Despite the lower cross-neutralizing titers induced by B/HPIV3 expressing S-6P from B.1.1.529/Omicron, a single intranasal dose of all three versions of B/HPIV3 vectors was protective against matched or heterologous WA1/2020, B.1.617.2/Delta or BA.1 (B.1.1.529.1)/Omicron challenge; hamsters were protected from challenge virus replication in the lungs, while low levels of challenge virus were detectable in the upper respiratory tract of a small number of animals. Immunization also protected against lung inflammatory response after challenge, with mild inflammatory cytokine induction associated with the slightly lower level of cross-protection of WA1/2020 and B.1.617.2/Delta variants against the BA.1/Omicron variant. Serum antibodies elicited by all vaccine candidates were broadly reactive against 20 antigenic variants, but the antigenic breadth of antibodies elicited by B/HPIV3-expressed S-6P from the ancestral or B.1.617.2/Delta variant exceeded that of the S-6P B.1.1.529/Omicron expressing vector. These results will guide development of intranasal B/HPIV3 vectors with S antigens matching circulating SARS-CoV-2 variants.","journal":"PLoS Pathogens","year":2025,"id":530653,"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":0.9527,"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":649457,"name":"Yumiko Matsuoka","orcid":"0000-0002-9227-4708","position":1,"is_corresponding":false},{"id":593615,"name":"Celia Santos","orcid":"0000-0003-2915-2879","position":2,"is_corresponding":false},{"id":346916,"name":"Cindy Luongo","orcid":"0000-0002-3830-3803","position":3,"is_corresponding":false},{"id":504922,"name":"Xueqiao Liu","orcid":"0000-0001-7652-241X","position":4,"is_corresponding":false},{"id":863442,"name":"Lijuan Yang","orcid":"0000-0002-7212-7110","position":5,"is_corresponding":false},{"id":1135505,"name":"Jaclyn A. Kaiser","orcid":null,"position":6,"is_corresponding":false},{"id":1338268,"name":"Eleanor F Duncan","orcid":null,"position":7,"is_corresponding":false},{"id":232893,"name":"Reed F. Johnson","orcid":"0000-0002-4312-0550","position":8,"is_corresponding":false},{"id":229156,"name":"I‐Ting Teng","orcid":"0000-0002-4704-7100","position":9,"is_corresponding":false},{"id":105633,"name":"Peter D. Kwong","orcid":"0000-0003-3560-232X","position":10,"is_corresponding":false},{"id":235602,"name":"Ursula J. Buchholz","orcid":"0000-0002-2329-3198","position":11,"is_corresponding":false},{"id":649460,"name":"Cyril Le Nouën","orcid":"0000-0002-5719-4112","position":12,"is_corresponding":false},{"id":649458,"name":"Hong-Su Park","orcid":"0000-0002-8423-2188","position":0,"is_corresponding":true}],"reference_count":51,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:51:05.836974Z","pmid":"40258004","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":[]}