Mucosal Influenza Vector Vaccine Carrying TB10.4 and HspX Antigens Provides Protection against <i>Mycobacterium tuberculosis</i> in Mice and Guinea Pigs
New strategies providing protection against tuberculosis (TB) are still pending. The airborne nature of Mycobacterium tuberculosis (<i>M.tb)</i> infection assumes that the mucosal delivery of the TB vaccine could be a more promising strategy than the systemic route of immunization. We de...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-04-01
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| Series: | Vaccines |
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| Online Access: | https://www.mdpi.com/2076-393X/9/4/394 |
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| author | Mariia Sergeeva Ekaterina Romanovskaya-Romanko Natalia Zabolotnyh Anastasia Pulkina Kirill Vasilyev Anna Polina Shurigina Janna Buzitskaya Yana Zabrodskaya Artem Fadeev Andrey Vasin Tatiana I. Vinogradova Marina A. Stukova |
| author_facet | Mariia Sergeeva Ekaterina Romanovskaya-Romanko Natalia Zabolotnyh Anastasia Pulkina Kirill Vasilyev Anna Polina Shurigina Janna Buzitskaya Yana Zabrodskaya Artem Fadeev Andrey Vasin Tatiana I. Vinogradova Marina A. Stukova |
| author_sort | Mariia Sergeeva |
| collection | DOAJ |
| description | New strategies providing protection against tuberculosis (TB) are still pending. The airborne nature of Mycobacterium tuberculosis (<i>M.tb)</i> infection assumes that the mucosal delivery of the TB vaccine could be a more promising strategy than the systemic route of immunization. We developed a mucosal TB vaccine candidate based on recombinant attenuated influenza vector (Flu/THSP) co-expressing truncated NS1 protein NS1(1–124) and a full-length TB10.4 and HspX proteins of <i>M.tb</i> within an NS1 protein open reading frame. The Flu/THSP vector was safe and stimulated a systemic TB-specific CD4+ and CD8+ T-cell immune response after intranasal immunization in mice. Double intranasal immunization with the Flu/THSP vector induced protection against two virulent <i>M.tb</i> strains equal to the effect of BCG subcutaneous injection in mice. In a guinea pig TB model, one intranasal immunization with Flu/THSP improved protection against <i>M.tb</i> when tested as a vaccine candidate for boosting BCG-primed immunity. Importantly, enhanced protection provided by a heterologous BCG-prime → Flu/THSP vector boost immunization scheme was associated with a significantly reduced lung and spleen bacterial burden (mean decrease of 0.77 lg CFU and 0.72 lg CFU, respectively) and improved lung pathology 8.5 weeks post-infection with virulent <i>M.tb</i> strain H37Rv. |
| first_indexed | 2024-03-10T12:16:00Z |
| format | Article |
| id | doaj.art-003c48119fca443ab1736fbff8f4ec55 |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-03-10T12:16:00Z |
| publishDate | 2021-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj.art-003c48119fca443ab1736fbff8f4ec552023-11-21T15:50:57ZengMDPI AGVaccines2076-393X2021-04-019439410.3390/vaccines9040394Mucosal Influenza Vector Vaccine Carrying TB10.4 and HspX Antigens Provides Protection against <i>Mycobacterium tuberculosis</i> in Mice and Guinea PigsMariia Sergeeva0Ekaterina Romanovskaya-Romanko1Natalia Zabolotnyh2Anastasia Pulkina3Kirill Vasilyev4Anna Polina Shurigina5Janna Buzitskaya6Yana Zabrodskaya7Artem Fadeev8Andrey Vasin9Tatiana I. Vinogradova10Marina A. Stukova11Smorodintsev Research Institute of Influenza of the Ministry of Health of the Russian Federation, 197376 St. Petersburg, RussiaSmorodintsev Research Institute of Influenza of the Ministry of Health of the Russian Federation, 197376 St. Petersburg, RussiaSaint-Petersburg State Research Institute of Phthisiopulmonology of the Ministry of Health of the Russian Federation, 191036 St. Petersburg, RussiaSmorodintsev Research Institute of Influenza of the Ministry of Health of the Russian Federation, 197376 St. Petersburg, RussiaSmorodintsev Research Institute of Influenza of the Ministry of Health of the Russian Federation, 197376 St. Petersburg, RussiaSmorodintsev Research Institute of Influenza of the Ministry of Health of the Russian Federation, 197376 St. Petersburg, RussiaSmorodintsev Research Institute of Influenza of the Ministry of Health of the Russian Federation, 197376 St. Petersburg, RussiaSmorodintsev Research Institute of Influenza of the Ministry of Health of the Russian Federation, 197376 St. Petersburg, RussiaSmorodintsev Research Institute of Influenza of the Ministry of Health of the Russian Federation, 197376 St. Petersburg, RussiaSmorodintsev Research Institute of Influenza of the Ministry of Health of the Russian Federation, 197376 St. Petersburg, RussiaSaint-Petersburg State Research Institute of Phthisiopulmonology of the Ministry of Health of the Russian Federation, 191036 St. Petersburg, RussiaSmorodintsev Research Institute of Influenza of the Ministry of Health of the Russian Federation, 197376 St. Petersburg, RussiaNew strategies providing protection against tuberculosis (TB) are still pending. The airborne nature of Mycobacterium tuberculosis (<i>M.tb)</i> infection assumes that the mucosal delivery of the TB vaccine could be a more promising strategy than the systemic route of immunization. We developed a mucosal TB vaccine candidate based on recombinant attenuated influenza vector (Flu/THSP) co-expressing truncated NS1 protein NS1(1–124) and a full-length TB10.4 and HspX proteins of <i>M.tb</i> within an NS1 protein open reading frame. The Flu/THSP vector was safe and stimulated a systemic TB-specific CD4+ and CD8+ T-cell immune response after intranasal immunization in mice. Double intranasal immunization with the Flu/THSP vector induced protection against two virulent <i>M.tb</i> strains equal to the effect of BCG subcutaneous injection in mice. In a guinea pig TB model, one intranasal immunization with Flu/THSP improved protection against <i>M.tb</i> when tested as a vaccine candidate for boosting BCG-primed immunity. Importantly, enhanced protection provided by a heterologous BCG-prime → Flu/THSP vector boost immunization scheme was associated with a significantly reduced lung and spleen bacterial burden (mean decrease of 0.77 lg CFU and 0.72 lg CFU, respectively) and improved lung pathology 8.5 weeks post-infection with virulent <i>M.tb</i> strain H37Rv.https://www.mdpi.com/2076-393X/9/4/394<i>M. tuberculosis</i> multistage vaccineTB10.4HspXinfluenza vectormucosal immunization |
| spellingShingle | Mariia Sergeeva Ekaterina Romanovskaya-Romanko Natalia Zabolotnyh Anastasia Pulkina Kirill Vasilyev Anna Polina Shurigina Janna Buzitskaya Yana Zabrodskaya Artem Fadeev Andrey Vasin Tatiana I. Vinogradova Marina A. Stukova Mucosal Influenza Vector Vaccine Carrying TB10.4 and HspX Antigens Provides Protection against <i>Mycobacterium tuberculosis</i> in Mice and Guinea Pigs Vaccines <i>M. tuberculosis</i> multistage vaccine TB10.4 HspX influenza vector mucosal immunization |
| title | Mucosal Influenza Vector Vaccine Carrying TB10.4 and HspX Antigens Provides Protection against <i>Mycobacterium tuberculosis</i> in Mice and Guinea Pigs |
| title_full | Mucosal Influenza Vector Vaccine Carrying TB10.4 and HspX Antigens Provides Protection against <i>Mycobacterium tuberculosis</i> in Mice and Guinea Pigs |
| title_fullStr | Mucosal Influenza Vector Vaccine Carrying TB10.4 and HspX Antigens Provides Protection against <i>Mycobacterium tuberculosis</i> in Mice and Guinea Pigs |
| title_full_unstemmed | Mucosal Influenza Vector Vaccine Carrying TB10.4 and HspX Antigens Provides Protection against <i>Mycobacterium tuberculosis</i> in Mice and Guinea Pigs |
| title_short | Mucosal Influenza Vector Vaccine Carrying TB10.4 and HspX Antigens Provides Protection against <i>Mycobacterium tuberculosis</i> in Mice and Guinea Pigs |
| title_sort | mucosal influenza vector vaccine carrying tb10 4 and hspx antigens provides protection against i mycobacterium tuberculosis i in mice and guinea pigs |
| topic | <i>M. tuberculosis</i> multistage vaccine TB10.4 HspX influenza vector mucosal immunization |
| url | https://www.mdpi.com/2076-393X/9/4/394 |
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