Intranasal Immunization with the Influenza A Virus Encoding Truncated NS1 Protein Protects Mice from Heterologous Challenge by Restraining the Inflammatory Response in the Lungs
Influenza viruses with an impaired NS1 protein are unable to antagonize the innate immune system and, therefore, are highly immunogenic because of the self-adjuvating effect. Hence, NS1-mutated viruses are considered promising candidates for the development of live-attenuated influenza vaccines and...
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MDPI AG
2021-03-01
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| Series: | Microorganisms |
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| Online Access: | https://www.mdpi.com/2076-2607/9/4/690 |
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| author | Kirill Vasilyev Anna-Polina Shurygina Maria Sergeeva Marina Stukova Andrej Egorov |
| author_facet | Kirill Vasilyev Anna-Polina Shurygina Maria Sergeeva Marina Stukova Andrej Egorov |
| author_sort | Kirill Vasilyev |
| collection | DOAJ |
| description | Influenza viruses with an impaired NS1 protein are unable to antagonize the innate immune system and, therefore, are highly immunogenic because of the self-adjuvating effect. Hence, NS1-mutated viruses are considered promising candidates for the development of live-attenuated influenza vaccines and viral vectors for intranasal administration. We investigated whether the immunogenic advantage of the virus expressing only the N-terminal half of the NS1 protein (124 a.a.) can be translated into the induction of protective immunity against a heterologous influenza virus in mice. We found that immunization with either the wild-type A/PR/8/34 (H1N1) influenza strain (A/PR8/NSfull) or its NS1-shortened counterpart (A/PR8/NS124) did not prevent the viral replication in the lungs after the challenge with the A/Aichi/2/68 (H3N2) virus. However, mice immunized with the NS1-shortened virus were better protected from lethality after the challenge with the heterologous virus. Besides showing the enhanced influenza-specific CD8<sup>+</sup> T-cellular response in the lungs, immunization with the A/PR8/NS124 virus resulted in reduced concentrations of proinflammatory cytokines and the lower extent of leukocyte infiltration in the lungs after the challenge compared to A/PR8/NSfull or the control group. The data show that intranasal immunization with the NS1-truncated virus may better induce not only effector T-cells but also certain immunoregulatory mechanisms, reducing the severity of the innate immune response after the heterologous challenge. |
| first_indexed | 2024-03-10T12:52:26Z |
| format | Article |
| id | doaj.art-a6581012bc8e4c0fb5662758d1f29c65 |
| institution | Directory Open Access Journal |
| issn | 2076-2607 |
| language | English |
| last_indexed | 2024-03-10T12:52:26Z |
| publishDate | 2021-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Microorganisms |
| spelling | doaj.art-a6581012bc8e4c0fb5662758d1f29c652023-11-21T13:00:07ZengMDPI AGMicroorganisms2076-26072021-03-019469010.3390/microorganisms9040690Intranasal Immunization with the Influenza A Virus Encoding Truncated NS1 Protein Protects Mice from Heterologous Challenge by Restraining the Inflammatory Response in the LungsKirill Vasilyev0Anna-Polina Shurygina1Maria Sergeeva2Marina Stukova3Andrej Egorov4Smorodintsev Research Institute of Influenza, 197022 St. Petersburg, RussiaSmorodintsev Research Institute of Influenza, 197022 St. Petersburg, RussiaSmorodintsev Research Institute of Influenza, 197022 St. Petersburg, RussiaSmorodintsev Research Institute of Influenza, 197022 St. Petersburg, RussiaSmorodintsev Research Institute of Influenza, 197022 St. Petersburg, RussiaInfluenza viruses with an impaired NS1 protein are unable to antagonize the innate immune system and, therefore, are highly immunogenic because of the self-adjuvating effect. Hence, NS1-mutated viruses are considered promising candidates for the development of live-attenuated influenza vaccines and viral vectors for intranasal administration. We investigated whether the immunogenic advantage of the virus expressing only the N-terminal half of the NS1 protein (124 a.a.) can be translated into the induction of protective immunity against a heterologous influenza virus in mice. We found that immunization with either the wild-type A/PR/8/34 (H1N1) influenza strain (A/PR8/NSfull) or its NS1-shortened counterpart (A/PR8/NS124) did not prevent the viral replication in the lungs after the challenge with the A/Aichi/2/68 (H3N2) virus. However, mice immunized with the NS1-shortened virus were better protected from lethality after the challenge with the heterologous virus. Besides showing the enhanced influenza-specific CD8<sup>+</sup> T-cellular response in the lungs, immunization with the A/PR8/NS124 virus resulted in reduced concentrations of proinflammatory cytokines and the lower extent of leukocyte infiltration in the lungs after the challenge compared to A/PR8/NSfull or the control group. The data show that intranasal immunization with the NS1-truncated virus may better induce not only effector T-cells but also certain immunoregulatory mechanisms, reducing the severity of the innate immune response after the heterologous challenge.https://www.mdpi.com/2076-2607/9/4/690influenza virusNS1 proteinimmune responseimmunogenicityflow cytometry |
| spellingShingle | Kirill Vasilyev Anna-Polina Shurygina Maria Sergeeva Marina Stukova Andrej Egorov Intranasal Immunization with the Influenza A Virus Encoding Truncated NS1 Protein Protects Mice from Heterologous Challenge by Restraining the Inflammatory Response in the Lungs Microorganisms influenza virus NS1 protein immune response immunogenicity flow cytometry |
| title | Intranasal Immunization with the Influenza A Virus Encoding Truncated NS1 Protein Protects Mice from Heterologous Challenge by Restraining the Inflammatory Response in the Lungs |
| title_full | Intranasal Immunization with the Influenza A Virus Encoding Truncated NS1 Protein Protects Mice from Heterologous Challenge by Restraining the Inflammatory Response in the Lungs |
| title_fullStr | Intranasal Immunization with the Influenza A Virus Encoding Truncated NS1 Protein Protects Mice from Heterologous Challenge by Restraining the Inflammatory Response in the Lungs |
| title_full_unstemmed | Intranasal Immunization with the Influenza A Virus Encoding Truncated NS1 Protein Protects Mice from Heterologous Challenge by Restraining the Inflammatory Response in the Lungs |
| title_short | Intranasal Immunization with the Influenza A Virus Encoding Truncated NS1 Protein Protects Mice from Heterologous Challenge by Restraining the Inflammatory Response in the Lungs |
| title_sort | intranasal immunization with the influenza a virus encoding truncated ns1 protein protects mice from heterologous challenge by restraining the inflammatory response in the lungs |
| topic | influenza virus NS1 protein immune response immunogenicity flow cytometry |
| url | https://www.mdpi.com/2076-2607/9/4/690 |
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