{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T05:28:25Z","timestamp":1786426105445,"version":"build-2736575974"},"reference-count":65,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,8]],"date-time":"2026-08-08T00:00:00Z","timestamp":1786147200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100017638","name":"Ministry of Health of the Russian Federation","doi-asserted-by":"crossref","award":["123021300194-6"],"award-info":[{"award-number":["123021300194-6"]}],"id":[{"id":"10.13039\/501100017638","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100017638","name":"Ministry of Health of the Russian Federation","doi-asserted-by":"crossref","award":["056-03-2021-059"],"award-info":[{"award-number":["056-03-2021-059"]}],"id":[{"id":"10.13039\/501100017638","id-type":"DOI","asserted-by":"crossref"}]},{"award":["123021300194-6"],"award-info":[{"award-number":["123021300194-6"]}],"id":[{"id":"https:\/\/ror.org\/01p8ehb87","id-type":"ROR","asserted-by":"publisher"}]},{"award":["056-03-2021-059"],"award-info":[{"award-number":["056-03-2021-059"]}],"id":[{"id":"https:\/\/ror.org\/01p8ehb87","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Introduction: The development of bivalent mucosal vaccines capable of providing protection against both influenza and SARS-CoV-2 is a major public health focus. While most COVID-19 vaccines target the spike (S) protein, the highly conserved nucleocapsid (N) protein represents a strategic target for cross-reactive, cell-mediated immunity. This study evaluates Corfluvec, an intranasal vaccine candidate based on an attenuated NS1-truncated influenza vector expressing a fragment of the SARS-CoV-2 N protein. Methods: Protective efficacy, including viral load and pathomorphological changes in the lungs and vessels, was evaluated in Syrian hamsters challenged with high and low doses of SARS-CoV-2 (lineage B.1.1). Cross-protective efficacy against homologous and heterologous influenza A strains (H1N1pdm09, H3N2, and A\/PR\/8\/1934) was tested in a lethal murine model. Additionally, immunogenicity of Corfluvec applied via human-compatible delivery device was tested in cynomolgus macaques (Macaca fascicularis). Results: In Syrian hamsters, vaccination significantly reduced viral loads in the lungs and nasal turbinates. Histopathological analysis revealed a preservation of lung vascular integrity: vaccinated animals showed stable CD31 expression and controlled Ki-67 proliferative activity, accompanied by a marked reduction in vasculitis and perivascular edema compared to placebo controls. In mice, the vaccine provided 100% protection against homologous and heterologous influenza virus challenges. In macaques, the two-dose intranasal immunization was well-tolerated and induced significant systemic IgG and mucosal sIgA responses, alongside robust N-specific IFN\u03b3+ T-cell activation. Conclusions: Corfluvec is a promising bivalent vaccine candidate that provides dual protection against influenza and COVID-19. Its ability to limit viral shedding from the upper respiratory tract and to mitigate SARS-CoV-2-induced pulmonary pathology, contributing to the preservation of lung vascular integrity, underscores the utility of mucosal immunization with Corfluvec as a valuable intranasal complement to current systemic vaccination strategies.<\/jats:p>","DOI":"10.3390\/vaccines14080684","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T09:24:53Z","timestamp":1786353893000},"page":"684","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Novel Intranasal Influenza-Vectored Vaccine Corfluvec Provides Protection Against Influenza and COVID-19, Mitigating SARS-CoV-2-Induced Lung Vascular Damage"],"prefix":"10.3390","volume":"14","author":[{"given":"Marina","family":"Stukova","sequence":"first","affiliation":[{"name":"Smorodintsev Research Institute of Influenza of the Ministry of Health of the Russian Federation, 197022 St. Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3685-7068","authenticated-orcid":false,"given":"Anna-Polina","family":"Shurygina","sequence":"additional","affiliation":[{"name":"Smorodintsev Research Institute of Influenza of the Ministry of Health of the Russian Federation, 197022 St. Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arman","family":"Muzhikyan","sequence":"additional","affiliation":[{"name":"Smorodintsev Research Institute of Influenza of the Ministry of Health of the Russian Federation, 197022 St. Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7560-398X","authenticated-orcid":false,"given":"Ekaterina","family":"Romanovskaya-Romanko","sequence":"additional","affiliation":[{"name":"Smorodintsev Research Institute of Influenza of the Ministry of Health of the Russian Federation, 197022 St. Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhanna","family":"Buzitskaya","sequence":"additional","affiliation":[{"name":"Smorodintsev Research Institute of Influenza of the Ministry of Health of the Russian Federation, 197022 St. Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7550-5519","authenticated-orcid":false,"given":"Marina","family":"Shuklina","sequence":"additional","affiliation":[{"name":"Smorodintsev Research Institute of Influenza of the Ministry of Health of the Russian Federation, 197022 St. Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasia","family":"Pulkina","sequence":"additional","affiliation":[{"name":"Smorodintsev Research Institute of Influenza of the Ministry of Health of the Russian Federation, 197022 St. Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daria","family":"Shamakova","sequence":"additional","affiliation":[{"name":"Smorodintsev Research Institute of Influenza of the Ministry of Health of the Russian Federation, 197022 St. Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirill","family":"Kryshen","sequence":"additional","affiliation":[{"name":"RMC \u201cHome of Pharmacy\u201d JSC, 188663 Kuzmolovsky, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0411-9896","authenticated-orcid":false,"given":"Mariia","family":"Sergeeva","sequence":"additional","affiliation":[{"name":"Smorodintsev Research Institute of Influenza of the Ministry of Health of the Russian Federation, 197022 St. Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dmitriy","family":"Lioznov","sequence":"additional","affiliation":[{"name":"Smorodintsev Research Institute of Influenza of the Ministry of Health of the Russian Federation, 197022 St. Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Sharma, A., Ahmad Farouk, I., and Lal, S.K. 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