Truncated NS1 Influenza A Virus Induces a Robust Antigen-Specific Tissue-Resident T-Cell Response and Promotes Inducible Bronchus-Associated Lymphoid Tissue Formation in Mice
Background: Influenza viruses with truncated NS1 proteins show promise as viral vectors and candidates for mucosal universal influenza vaccines. These mutant NS1 viruses, which lack the N-terminal half of the NS1 protein (124 a.a.), are unable to antagonise the innate immune response. This creates a...
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2025-01-01
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| author | Anna-Polina Shurygina Marina Shuklina Olga Ozhereleva Ekaterina Romanovskaya-Romanko Sofia Kovaleva Andrej Egorov Dmitry Lioznov Marina Stukova |
| author_facet | Anna-Polina Shurygina Marina Shuklina Olga Ozhereleva Ekaterina Romanovskaya-Romanko Sofia Kovaleva Andrej Egorov Dmitry Lioznov Marina Stukova |
| author_sort | Anna-Polina Shurygina |
| collection | DOAJ |
| description | Background: Influenza viruses with truncated NS1 proteins show promise as viral vectors and candidates for mucosal universal influenza vaccines. These mutant NS1 viruses, which lack the N-terminal half of the NS1 protein (124 a.a.), are unable to antagonise the innate immune response. This creates a self-adjuvant effect enhancing heterologous protection by inducing a robust CD8+ T-cell response together with immunoregulatory mechanisms. However, the effects of NS1 modifications on T-follicular helper (Tfh) and B-cell responses remain less understood. Methods: C57bl/6 mice were immunised intranasally with 10 μL of either an influenza virus containing a truncated NS1 protein (PR8/NS124), a cold-adapted influenza virus with a full-length NS1 (caPR8/NSfull), or a wild-type virus (PR8/NSfull). Immune responses were assessed on days 8 and 28 post-immunisation by flow cytometry, ELISA, and HAI assay. Results: In this study, we demonstrate that intranasal immunisation with PR8/NS124 significantly increases tissue-resident CD4+ and CD8+ T cells in the lungs and activates Tfh cells in regional lymph nodes as early as day 8 post-immunisation. These effects are not observed in mice immunised with caPR8/NSfull or PR8/NSfull. Notably, PR8/NS124 immunisation also leads to the development of inducible bronchus-associated lymphoid tissue (iBALT) in the lungs by day 28, characterised by the presence of antigen-specific Tfh cells and GL7+Fas+ germinal centre B cells. Conclusions: Our findings further underscore the potential of NS1-truncated influenza viruses to drive robust mucosal immune responses and enhance vaccine efficacy. |
| format | Article |
| id | doaj-art-84f4890179b343d2aad11ccc998f16ad |
| institution | Kabale University |
| issn | 2076-393X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj-art-84f4890179b343d2aad11ccc998f16ad2025-01-24T13:51:48ZengMDPI AGVaccines2076-393X2025-01-011315810.3390/vaccines13010058Truncated NS1 Influenza A Virus Induces a Robust Antigen-Specific Tissue-Resident T-Cell Response and Promotes Inducible Bronchus-Associated Lymphoid Tissue Formation in MiceAnna-Polina Shurygina0Marina Shuklina1Olga Ozhereleva2Ekaterina Romanovskaya-Romanko3Sofia Kovaleva4Andrej Egorov5Dmitry Lioznov6Marina Stukova7Smorodintsev Research Institute of Influenza, The Ministry of Health of the Russian Federation, Saint-Petersburg 197022, RussiaSmorodintsev Research Institute of Influenza, The Ministry of Health of the Russian Federation, Saint-Petersburg 197022, RussiaSmorodintsev Research Institute of Influenza, The Ministry of Health of the Russian Federation, Saint-Petersburg 197022, RussiaSmorodintsev Research Institute of Influenza, The Ministry of Health of the Russian Federation, Saint-Petersburg 197022, RussiaSmorodintsev Research Institute of Influenza, The Ministry of Health of the Russian Federation, Saint-Petersburg 197022, RussiaSmorodintsev Research Institute of Influenza, The Ministry of Health of the Russian Federation, Saint-Petersburg 197022, RussiaSmorodintsev Research Institute of Influenza, The Ministry of Health of the Russian Federation, Saint-Petersburg 197022, RussiaSmorodintsev Research Institute of Influenza, The Ministry of Health of the Russian Federation, Saint-Petersburg 197022, RussiaBackground: Influenza viruses with truncated NS1 proteins show promise as viral vectors and candidates for mucosal universal influenza vaccines. These mutant NS1 viruses, which lack the N-terminal half of the NS1 protein (124 a.a.), are unable to antagonise the innate immune response. This creates a self-adjuvant effect enhancing heterologous protection by inducing a robust CD8+ T-cell response together with immunoregulatory mechanisms. However, the effects of NS1 modifications on T-follicular helper (Tfh) and B-cell responses remain less understood. Methods: C57bl/6 mice were immunised intranasally with 10 μL of either an influenza virus containing a truncated NS1 protein (PR8/NS124), a cold-adapted influenza virus with a full-length NS1 (caPR8/NSfull), or a wild-type virus (PR8/NSfull). Immune responses were assessed on days 8 and 28 post-immunisation by flow cytometry, ELISA, and HAI assay. Results: In this study, we demonstrate that intranasal immunisation with PR8/NS124 significantly increases tissue-resident CD4+ and CD8+ T cells in the lungs and activates Tfh cells in regional lymph nodes as early as day 8 post-immunisation. These effects are not observed in mice immunised with caPR8/NSfull or PR8/NSfull. Notably, PR8/NS124 immunisation also leads to the development of inducible bronchus-associated lymphoid tissue (iBALT) in the lungs by day 28, characterised by the presence of antigen-specific Tfh cells and GL7+Fas+ germinal centre B cells. Conclusions: Our findings further underscore the potential of NS1-truncated influenza viruses to drive robust mucosal immune responses and enhance vaccine efficacy.https://www.mdpi.com/2076-393X/13/1/58influenzaintranasal immunizationtruncated NS1 proteinLAIVuniversal influenza vaccinetissue-resident T cells |
| spellingShingle | Anna-Polina Shurygina Marina Shuklina Olga Ozhereleva Ekaterina Romanovskaya-Romanko Sofia Kovaleva Andrej Egorov Dmitry Lioznov Marina Stukova Truncated NS1 Influenza A Virus Induces a Robust Antigen-Specific Tissue-Resident T-Cell Response and Promotes Inducible Bronchus-Associated Lymphoid Tissue Formation in Mice Vaccines influenza intranasal immunization truncated NS1 protein LAIV universal influenza vaccine tissue-resident T cells |
| title | Truncated NS1 Influenza A Virus Induces a Robust Antigen-Specific Tissue-Resident T-Cell Response and Promotes Inducible Bronchus-Associated Lymphoid Tissue Formation in Mice |
| title_full | Truncated NS1 Influenza A Virus Induces a Robust Antigen-Specific Tissue-Resident T-Cell Response and Promotes Inducible Bronchus-Associated Lymphoid Tissue Formation in Mice |
| title_fullStr | Truncated NS1 Influenza A Virus Induces a Robust Antigen-Specific Tissue-Resident T-Cell Response and Promotes Inducible Bronchus-Associated Lymphoid Tissue Formation in Mice |
| title_full_unstemmed | Truncated NS1 Influenza A Virus Induces a Robust Antigen-Specific Tissue-Resident T-Cell Response and Promotes Inducible Bronchus-Associated Lymphoid Tissue Formation in Mice |
| title_short | Truncated NS1 Influenza A Virus Induces a Robust Antigen-Specific Tissue-Resident T-Cell Response and Promotes Inducible Bronchus-Associated Lymphoid Tissue Formation in Mice |
| title_sort | truncated ns1 influenza a virus induces a robust antigen specific tissue resident t cell response and promotes inducible bronchus associated lymphoid tissue formation in mice |
| topic | influenza intranasal immunization truncated NS1 protein LAIV universal influenza vaccine tissue-resident T cells |
| url | https://www.mdpi.com/2076-393X/13/1/58 |
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