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In this study, we employed reverse genetics to generate a chimeric influenza virus expressing neuraminidase\u20103F protein conjugate with three repeats of the RSV F protein protective epitope inserted into the NA gene of A\/California\/7\/2009 ca (CA\/AA ca), resulting in rFlu\/RSV\/NA\u20103F (hereafter, rFRN3). The expression of NA\u20103F protein was confirmed by Western blotting. The morphology and temperature\u2010sensitive phenotype of rFRN3 were similar to CA\/AA ca. Its immunogenicity and protective efficiency were evaluated in BALB\/c mice and cotton rats. Intranasal administration of rFRN3 elicited robust humoral, cellular, and to some extent, mucosal immune responses. Compared to controls, rFRN3 protected animals from RSV infection, attenuated lung injury, and reduced viral titers in the nose and lungs post\u2010RSV challenge. These results demonstrate that rFRN3 can trigger RSV\u2010specific immune responses and thus exhibits potent protective efficacy. The \u201cdual vaccine\u201d approach of a cold\u2010adapted influenza vector RSV vaccine will improve the prophylaxis of influenza and RSV infection. rFRN3 thus warrants further clinical investigations as a candidate RSV vaccine.<\/jats:p>","DOI":"10.1002\/jmv.29308","type":"journal-article","created":{"date-parts":[[2024,7,15]],"date-time":"2024-07-15T11:01:58Z","timestamp":1721041318000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Cold\u2010adapted influenza\u2010vectored RSV vaccine protects BALB\/c mice and cotton rats from RSV challenge"],"prefix":"10.1002","volume":"96","author":[{"given":"Yongru","family":"Xu","sequence":"first","affiliation":[{"name":"The First Medical Center of Chinese PLA General Hospital Beijing China"},{"name":"Faculty of Hepato\u2010Pancreato\u2010Biliary Surgery Chinese PLA General Hospital Beijing China"},{"name":"Key Laboratory of Digital Hepatobiliary Surgery, PLA Institute of Hepatobiliary Surgery of Chinese PLA Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Sun","sequence":"additional","affiliation":[{"name":"Fifth Medical Center of Chinese PLA General Hospital Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhifang","family":"Bai","sequence":"additional","affiliation":[{"name":"Fifth Medical Center of Chinese PLA General Hospital Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengrong","family":"Bian","sequence":"additional","affiliation":[{"name":"Fifth Medical Center of Chinese PLA General Hospital Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiliang","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology Academy of Military Medical Sciences Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongpeng","family":"Zhao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology Academy of Military Medical Sciences Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7481-5056","authenticated-orcid":false,"given":"Penghui","family":"Yang","sequence":"additional","affiliation":[{"name":"The First Medical Center of Chinese PLA General Hospital Beijing China"},{"name":"Faculty of Hepato\u2010Pancreato\u2010Biliary Surgery Chinese PLA General Hospital Beijing China"},{"name":"Key Laboratory of Digital Hepatobiliary Surgery, PLA Institute of Hepatobiliary Surgery of Chinese PLA Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,7,15]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(22)00478-0"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiab040"},{"key":"e_1_2_9_4_1","unstructured":"National Institute of Allergy and Infectious Diseases. 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