{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:15:38Z","timestamp":1787030138473,"version":"build-2736575974"},"reference-count":47,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2024,12,28]],"date-time":"2024-12-28T00:00:00Z","timestamp":1735344000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Health of the Russian Federation","award":["056-00012-23-01"],"award-info":[{"award-number":["056-00012-23-01"]}]},{"name":"Ministry of Health of the Russian Federation","award":["056-03-2021-059"],"award-info":[{"award-number":["056-03-2021-059"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Background\/Objectives: Intranasal vaccination enhances protection against respiratory viruses by providing stimuli to the immune system at the primary site of infection, promoting a balanced and effective response. Influenza vectors with truncated NS1 are a promising vaccine approach that ensures a pronounced local CD8+ T-cellular immune response. Here, we describe the protective and immunomodulating properties of an influenza vector FluVec-N carrying the C-terminal fragment of the SARS-CoV-2 nucleoprotein within a truncated NS1 open reading frame. Methods: We generated several FluVec-N recombinant vectors by reverse genetics and confirmed the vector\u2019s genetic stability, antigen expression in vitro, attenuation, and immunogenicity in a mouse model. We tested the protective potential of FluVec-N intranasal immunization in na\u00efve mice and seropositive Th2-prone mice, primed with aluminium-adjuvanted inactivated SARS-CoV-2. Immune response in immunized and challenged mice was analyzed through serological methods and flow cytometry. Results: Double intranasal immunization of na\u00efve mice with FluVec-N reduced weight loss and viral load in the lungs following infection with the SARS-CoV-2 beta variant. Mice primed with alum-adjuvanted inactivated coronavirus experienced substantial early weight loss and eosinophilia in the lungs during infection, demonstrating signs of enhanced disease. A single intranasal boost immunization with FluVec-N prevented the disease enhancement in primed mice by modulating the local immune response. Protection was associated with the formation of specific IgA and the early activation of virus-specific effector and resident CD8+ lymphocytes in mouse lungs. Conclusions: Our study supports the potential of immunization with influenza vector vaccines to prevent respiratory diseases and associated immunopathology.<\/jats:p>","DOI":"10.3390\/vaccines13010015","type":"journal-article","created":{"date-parts":[[2024,12,31]],"date-time":"2024-12-31T07:00:37Z","timestamp":1735628437000},"page":"15","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Mucosal Immunization with an Influenza Vector Carrying SARS-CoV-2 N Protein Protects Na\u00efve Mice and Prevents Disease Enhancement in Seropositive Th2-Prone Mice"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0411-9896","authenticated-orcid":false,"given":"Mariia V.","family":"Sergeeva","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\/0000-0002-7750-9652","authenticated-orcid":false,"given":"Kirill","family":"Vasilev","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"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1050-5817","authenticated-orcid":false,"given":"Nikita","family":"Yolshin","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"}]},{"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\/0000-0003-3643-7354","authenticated-orcid":false,"given":"Dmitry","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"}]},{"given":"Marina","family":"Stukova","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":[[2024,12,28]]},"reference":[{"key":"ref_1","unstructured":"Holder, J. 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