Enhancement of systemic and lung-localized CD4<sup>+</sup> T-cell immune responses by truncation of NS1 protein of a seasonal live influenza vaccine strain
Introduction. There is a large variety of licensed influenza vaccines worldwide, but their common limitation is rather narrow specificity and inability to protect against antigenic-drift variants of influenza virus. Therefore, optimization of immunogenic and cross-protective properties of licensed i...
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Central Research Institute for Epidemiology
2024-11-01
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| Series: | Журнал микробиологии, эпидемиологии и иммунобиологии |
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| Online Access: | https://microbiol.crie.ru/jour/article/viewFile/18682/1518 |
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| author | Polina I. Prokopenko Ekaterina A. Stepanova Victoria A. Matyushenko Alexandra Ya. Rak Anna K. Chistyakova Arina D. Kostromitina Tatyana S. Kotomina Igor V. Kudryavtsev Artem A. Rubinstein Alexey S. Komlev Larisa G. Rudenko Irina N. Isakova-Sivak |
| author_facet | Polina I. Prokopenko Ekaterina A. Stepanova Victoria A. Matyushenko Alexandra Ya. Rak Anna K. Chistyakova Arina D. Kostromitina Tatyana S. Kotomina Igor V. Kudryavtsev Artem A. Rubinstein Alexey S. Komlev Larisa G. Rudenko Irina N. Isakova-Sivak |
| author_sort | Polina I. Prokopenko |
| collection | DOAJ |
| description | Introduction. There is a large variety of licensed influenza vaccines worldwide, but their common limitation is rather narrow specificity and inability to protect against antigenic-drift variants of influenza virus. Therefore, optimization of immunogenic and cross-protective properties of licensed influenza vaccines is an urgent priority of public health agenda. One such approach is to modulate the immunogenic properties of live attenuated influenza vaccine (LAIV) by truncating the open reading frame of influenza virus non-structural protein 1 (NS1). The main objective of this study is to evaluate the immunogenic properties of the H1N1 seasonal LAIV strain by truncation of the NS1 protein to 126 amino acides.
Materials and methods. Using reverse genetics technique, two H1N1 LAIV strains with full-length and truncated NS1 protein with three consecutive stop codons added after the 126th amino acid residue were obtained.C57BL/6J mice were immunized intranasally with the vaccine candidates, twice at a three-week interval. Seven days after the second immunization, cells were isolated from spleen and lung tissues and stimulated with whole wild-type H1N1 influenza virus. Levels of systemic and tissue-resident cytokine-producing CD4+ and CD8+ memory T cells were assessed by intracellular cytokine staining assay with flow cytometry. Replication of engineered vaccine strains in in vitro and in vivo systems was also evaluated.
Results. Truncation of NS1 protein of the LAIV strain significantly increased the levels of virus-specific CD4+ effector memory T cells in spleens and the levels of CD4+ tissue-resident memory T cells in lungs of mice after two-dose immunization, indicating a higher potential for protection against influenza infection of the LAIV NS126 vaccine strain compared to the classical variant of LAIV. Importantly, the LAIV NS126 strain also had a more pronounced attenuated phenotype in mice than its classical counterpart. |
| format | Article |
| id | doaj-art-b48f4e7aac934b85bda7bca76e59156e |
| institution | Kabale University |
| issn | 0372-9311 2686-7613 |
| language | Russian |
| publishDate | 2024-11-01 |
| publisher | Central Research Institute for Epidemiology |
| record_format | Article |
| series | Журнал микробиологии, эпидемиологии и иммунобиологии |
| spelling | doaj-art-b48f4e7aac934b85bda7bca76e59156e2025-01-09T20:09:08ZrusCentral Research Institute for EpidemiologyЖурнал микробиологии, эпидемиологии и иммунобиологии0372-93112686-76132024-11-01101561962710.36233/0372-9311-5822783Enhancement of systemic and lung-localized CD4<sup>+</sup> T-cell immune responses by truncation of NS1 protein of a seasonal live influenza vaccine strainPolina I. Prokopenko0https://orcid.org/0000-0002-7247-979XEkaterina A. Stepanova1https://orcid.org/0000-0002-8670-8645Victoria A. Matyushenko2https://orcid.org/0000-0002-4698-6085Alexandra Ya. Rak3https://orcid.org/0000-0001-5552-9874Anna K. Chistyakova4https://orcid.org/0000-0001-9541-5636Arina D. Kostromitina5https://orcid.org/0000-0001-5432-0171Tatyana S. Kotomina6https://orcid.org/0000-0001-9999-089XIgor V. Kudryavtsev7https://orcid.org/0000-0001-7204-7850Artem A. Rubinstein8https://orcid.org/0000-0002-8493-5211Alexey S. Komlev9https://orcid.org/0000-0001-9111-0755Larisa G. Rudenko10https://orcid.org/0000-0002-0107-9959Irina N. Isakova-Sivak11https://orcid.org/0000-0002-2801-1508Institute of Experimental MedicineInstitute of Experimental MedicineInstitute of Experimental MedicineInstitute of Experimental MedicineInstitute of Experimental MedicineInstitute of Experimental MedicineInstitute of Experimental MedicineInstitute of Experimental MedicineInstitute of Experimental MedicineInstitute of Experimental MedicineInstitute of Experimental MedicineInstitute of Experimental MedicineIntroduction. There is a large variety of licensed influenza vaccines worldwide, but their common limitation is rather narrow specificity and inability to protect against antigenic-drift variants of influenza virus. Therefore, optimization of immunogenic and cross-protective properties of licensed influenza vaccines is an urgent priority of public health agenda. One such approach is to modulate the immunogenic properties of live attenuated influenza vaccine (LAIV) by truncating the open reading frame of influenza virus non-structural protein 1 (NS1). The main objective of this study is to evaluate the immunogenic properties of the H1N1 seasonal LAIV strain by truncation of the NS1 protein to 126 amino acides. Materials and methods. Using reverse genetics technique, two H1N1 LAIV strains with full-length and truncated NS1 protein with three consecutive stop codons added after the 126th amino acid residue were obtained.C57BL/6J mice were immunized intranasally with the vaccine candidates, twice at a three-week interval. Seven days after the second immunization, cells were isolated from spleen and lung tissues and stimulated with whole wild-type H1N1 influenza virus. Levels of systemic and tissue-resident cytokine-producing CD4+ and CD8+ memory T cells were assessed by intracellular cytokine staining assay with flow cytometry. Replication of engineered vaccine strains in in vitro and in vivo systems was also evaluated. Results. Truncation of NS1 protein of the LAIV strain significantly increased the levels of virus-specific CD4+ effector memory T cells in spleens and the levels of CD4+ tissue-resident memory T cells in lungs of mice after two-dose immunization, indicating a higher potential for protection against influenza infection of the LAIV NS126 vaccine strain compared to the classical variant of LAIV. Importantly, the LAIV NS126 strain also had a more pronounced attenuated phenotype in mice than its classical counterpart.https://microbiol.crie.ru/jour/article/viewFile/18682/1518influenza viruslive attenuated influenza vaccinens1 proteinmemory t cellstissue-resident memory t cellstissue-resident memory t cellscd4+ т cells, cd8+ т cells |
| spellingShingle | Polina I. Prokopenko Ekaterina A. Stepanova Victoria A. Matyushenko Alexandra Ya. Rak Anna K. Chistyakova Arina D. Kostromitina Tatyana S. Kotomina Igor V. Kudryavtsev Artem A. Rubinstein Alexey S. Komlev Larisa G. Rudenko Irina N. Isakova-Sivak Enhancement of systemic and lung-localized CD4<sup>+</sup> T-cell immune responses by truncation of NS1 protein of a seasonal live influenza vaccine strain Журнал микробиологии, эпидемиологии и иммунобиологии influenza virus live attenuated influenza vaccine ns1 protein memory t cells tissue-resident memory t cells tissue-resident memory t cells cd4+ т cells, cd8+ т cells |
| title | Enhancement of systemic and lung-localized CD4<sup>+</sup> T-cell immune responses by truncation of NS1 protein of a seasonal live influenza vaccine strain |
| title_full | Enhancement of systemic and lung-localized CD4<sup>+</sup> T-cell immune responses by truncation of NS1 protein of a seasonal live influenza vaccine strain |
| title_fullStr | Enhancement of systemic and lung-localized CD4<sup>+</sup> T-cell immune responses by truncation of NS1 protein of a seasonal live influenza vaccine strain |
| title_full_unstemmed | Enhancement of systemic and lung-localized CD4<sup>+</sup> T-cell immune responses by truncation of NS1 protein of a seasonal live influenza vaccine strain |
| title_short | Enhancement of systemic and lung-localized CD4<sup>+</sup> T-cell immune responses by truncation of NS1 protein of a seasonal live influenza vaccine strain |
| title_sort | enhancement of systemic and lung localized cd4 sup sup t cell immune responses by truncation of ns1 protein of a seasonal live influenza vaccine strain |
| topic | influenza virus live attenuated influenza vaccine ns1 protein memory t cells tissue-resident memory t cells tissue-resident memory t cells cd4+ т cells, cd8+ т cells |
| url | https://microbiol.crie.ru/jour/article/viewFile/18682/1518 |
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