Mucosal Immunization with an Influenza Vector Carrying SARS-CoV-2 N Protein Protects Naïve Mice and Prevents Disease Enhancement in Seropositive Th2-Prone Mice
<b>Background/Objectives:</b> 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 appro...
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MDPI AG
2024-12-01
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| Series: | Vaccines |
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| Online Access: | https://www.mdpi.com/2076-393X/13/1/15 |
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| author | Mariia V. Sergeeva Kirill Vasilev Ekaterina Romanovskaya-Romanko Nikita Yolshin Anastasia Pulkina Daria Shamakova Anna-Polina Shurygina Arman Muzhikyan Dmitry Lioznov Marina Stukova |
| author_facet | Mariia V. Sergeeva Kirill Vasilev Ekaterina Romanovskaya-Romanko Nikita Yolshin Anastasia Pulkina Daria Shamakova Anna-Polina Shurygina Arman Muzhikyan Dmitry Lioznov Marina Stukova |
| author_sort | Mariia V. Sergeeva |
| collection | DOAJ |
| description | <b>Background/Objectives:</b> 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. <b>Methods</b>: We generated several FluVec-N recombinant vectors by reverse genetics and confirmed the vector’s genetic stability, antigen expression in vitro, attenuation, and immunogenicity in a mouse model. We tested the protective potential of FluVec-N intranasal immunization in naïve 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. <b>Results</b>: Double intranasal immunization of naïve 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. <b>Conclusions</b>: Our study supports the potential of immunization with influenza vector vaccines to prevent respiratory diseases and associated immunopathology. |
| format | Article |
| id | doaj-art-a3ea74ad3d0245e2a934f3565f052e7a |
| institution | Kabale University |
| issn | 2076-393X |
| language | English |
| publishDate | 2024-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj-art-a3ea74ad3d0245e2a934f3565f052e7a2025-01-24T13:51:40ZengMDPI AGVaccines2076-393X2024-12-011311510.3390/vaccines13010015Mucosal Immunization with an Influenza Vector Carrying SARS-CoV-2 N Protein Protects Naïve Mice and Prevents Disease Enhancement in Seropositive Th2-Prone MiceMariia V. Sergeeva0Kirill Vasilev1Ekaterina Romanovskaya-Romanko2Nikita Yolshin3Anastasia Pulkina4Daria Shamakova5Anna-Polina Shurygina6Arman Muzhikyan7Dmitry Lioznov8Marina Stukova9Smorodintsev Research Institute of Influenza of the Ministry of Health of the Russian Federation, 197022 St. Petersburg, RussiaSmorodintsev Research Institute of Influenza of the Ministry of Health of the Russian Federation, 197022 St. Petersburg, RussiaSmorodintsev Research Institute of Influenza of the Ministry of Health of the Russian Federation, 197022 St. Petersburg, RussiaSmorodintsev Research Institute of Influenza of the Ministry of Health of the Russian Federation, 197022 St. Petersburg, RussiaSmorodintsev Research Institute of Influenza of the Ministry of Health of the Russian Federation, 197022 St. Petersburg, RussiaSmorodintsev Research Institute of Influenza of the Ministry of Health of the Russian Federation, 197022 St. Petersburg, RussiaSmorodintsev Research Institute of Influenza of the Ministry of Health of the Russian Federation, 197022 St. Petersburg, RussiaSmorodintsev Research Institute of Influenza of the Ministry of Health of the Russian Federation, 197022 St. Petersburg, RussiaSmorodintsev Research Institute of Influenza of the Ministry of Health of the Russian Federation, 197022 St. Petersburg, RussiaSmorodintsev Research Institute of Influenza of the Ministry of Health of the Russian Federation, 197022 St. Petersburg, Russia<b>Background/Objectives:</b> 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. <b>Methods</b>: We generated several FluVec-N recombinant vectors by reverse genetics and confirmed the vector’s genetic stability, antigen expression in vitro, attenuation, and immunogenicity in a mouse model. We tested the protective potential of FluVec-N intranasal immunization in naïve 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. <b>Results</b>: Double intranasal immunization of naïve 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. <b>Conclusions</b>: Our study supports the potential of immunization with influenza vector vaccines to prevent respiratory diseases and associated immunopathology.https://www.mdpi.com/2076-393X/13/1/15influenza vectormucosal vaccineSARS-CoV-2inactivated vaccineVAERD |
| spellingShingle | Mariia V. Sergeeva Kirill Vasilev Ekaterina Romanovskaya-Romanko Nikita Yolshin Anastasia Pulkina Daria Shamakova Anna-Polina Shurygina Arman Muzhikyan Dmitry Lioznov Marina Stukova Mucosal Immunization with an Influenza Vector Carrying SARS-CoV-2 N Protein Protects Naïve Mice and Prevents Disease Enhancement in Seropositive Th2-Prone Mice Vaccines influenza vector mucosal vaccine SARS-CoV-2 inactivated vaccine VAERD |
| title | Mucosal Immunization with an Influenza Vector Carrying SARS-CoV-2 N Protein Protects Naïve Mice and Prevents Disease Enhancement in Seropositive Th2-Prone Mice |
| title_full | Mucosal Immunization with an Influenza Vector Carrying SARS-CoV-2 N Protein Protects Naïve Mice and Prevents Disease Enhancement in Seropositive Th2-Prone Mice |
| title_fullStr | Mucosal Immunization with an Influenza Vector Carrying SARS-CoV-2 N Protein Protects Naïve Mice and Prevents Disease Enhancement in Seropositive Th2-Prone Mice |
| title_full_unstemmed | Mucosal Immunization with an Influenza Vector Carrying SARS-CoV-2 N Protein Protects Naïve Mice and Prevents Disease Enhancement in Seropositive Th2-Prone Mice |
| title_short | Mucosal Immunization with an Influenza Vector Carrying SARS-CoV-2 N Protein Protects Naïve Mice and Prevents Disease Enhancement in Seropositive Th2-Prone Mice |
| title_sort | mucosal immunization with an influenza vector carrying sars cov 2 n protein protects naive mice and prevents disease enhancement in seropositive th2 prone mice |
| topic | influenza vector mucosal vaccine SARS-CoV-2 inactivated vaccine VAERD |
| url | https://www.mdpi.com/2076-393X/13/1/15 |
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