{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T01:13:43Z","timestamp":1790298823415,"version":"4.1.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1012585","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T00:00:00Z","timestamp":1746489600000}}],"reference-count":52,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2025,4,21]],"date-time":"2025-04-21T00:00:00Z","timestamp":1745193600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"DOI":"10.13039\/100006492","name":"Division of Intramural Research, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["ZIA AI001298-05"],"award-info":[{"award-number":["ZIA AI001298-05"]}],"id":[{"id":"10.13039\/100006492","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016820","name":"Vaccine Research Center","doi-asserted-by":"publisher","award":["ZIC AI005111-14"],"award-info":[{"award-number":["ZIC AI005111-14"]}],"id":[{"id":"10.13039\/100016820","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.1371\/journal.ppat.1012585","type":"journal-article","created":{"date-parts":[[2025,4,21]],"date-time":"2025-04-21T13:52:07Z","timestamp":1745243527000},"page":"e1012585","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":6,"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 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