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Mucosal Influenza Vector Vaccine Carrying TB10.4 and HspX Antigens Provides Protection against Mycobacterium tuberculosis in Mice and Guinea Pigs
New strategies providing protection against tuberculosis (TB) are still pending. The airborne nature of Mycobacterium tuberculosis (M.tb) 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 T...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8073308/ https://www.ncbi.nlm.nih.gov/pubmed/33923548 http://dx.doi.org/10.3390/vaccines9040394 |
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author | Sergeeva, Mariia Romanovskaya-Romanko, Ekaterina Zabolotnyh, Natalia Pulkina, Anastasia Vasilyev, Kirill Shurigina, Anna Polina Buzitskaya, Janna Zabrodskaya, Yana Fadeev, Artem Vasin, Andrey Vinogradova, Tatiana I. Stukova, Marina A. |
author_facet | Sergeeva, Mariia Romanovskaya-Romanko, Ekaterina Zabolotnyh, Natalia Pulkina, Anastasia Vasilyev, Kirill Shurigina, Anna Polina Buzitskaya, Janna Zabrodskaya, Yana Fadeev, Artem Vasin, Andrey Vinogradova, Tatiana I. Stukova, Marina A. |
author_sort | Sergeeva, Mariia |
collection | PubMed |
description | New strategies providing protection against tuberculosis (TB) are still pending. The airborne nature of Mycobacterium tuberculosis (M.tb) 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 M.tb 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 M.tb 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 M.tb 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 M.tb strain H37Rv. |
format | Online Article Text |
id | pubmed-8073308 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-80733082021-04-27 Mucosal Influenza Vector Vaccine Carrying TB10.4 and HspX Antigens Provides Protection against Mycobacterium tuberculosis in Mice and Guinea Pigs Sergeeva, Mariia Romanovskaya-Romanko, Ekaterina Zabolotnyh, Natalia Pulkina, Anastasia Vasilyev, Kirill Shurigina, Anna Polina Buzitskaya, Janna Zabrodskaya, Yana Fadeev, Artem Vasin, Andrey Vinogradova, Tatiana I. Stukova, Marina A. Vaccines (Basel) Article New strategies providing protection against tuberculosis (TB) are still pending. The airborne nature of Mycobacterium tuberculosis (M.tb) 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 M.tb 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 M.tb 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 M.tb 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 M.tb strain H37Rv. MDPI 2021-04-16 /pmc/articles/PMC8073308/ /pubmed/33923548 http://dx.doi.org/10.3390/vaccines9040394 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Sergeeva, Mariia Romanovskaya-Romanko, Ekaterina Zabolotnyh, Natalia Pulkina, Anastasia Vasilyev, Kirill Shurigina, Anna Polina Buzitskaya, Janna Zabrodskaya, Yana Fadeev, Artem Vasin, Andrey Vinogradova, Tatiana I. Stukova, Marina A. Mucosal Influenza Vector Vaccine Carrying TB10.4 and HspX Antigens Provides Protection against Mycobacterium tuberculosis in Mice and Guinea Pigs |
title | Mucosal Influenza Vector Vaccine Carrying TB10.4 and HspX Antigens Provides Protection against Mycobacterium tuberculosis in Mice and Guinea Pigs |
title_full | Mucosal Influenza Vector Vaccine Carrying TB10.4 and HspX Antigens Provides Protection against Mycobacterium tuberculosis in Mice and Guinea Pigs |
title_fullStr | Mucosal Influenza Vector Vaccine Carrying TB10.4 and HspX Antigens Provides Protection against Mycobacterium tuberculosis in Mice and Guinea Pigs |
title_full_unstemmed | Mucosal Influenza Vector Vaccine Carrying TB10.4 and HspX Antigens Provides Protection against Mycobacterium tuberculosis in Mice and Guinea Pigs |
title_short | Mucosal Influenza Vector Vaccine Carrying TB10.4 and HspX Antigens Provides Protection against Mycobacterium tuberculosis in Mice and Guinea Pigs |
title_sort | mucosal influenza vector vaccine carrying tb10.4 and hspx antigens provides protection against mycobacterium tuberculosis in mice and guinea pigs |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8073308/ https://www.ncbi.nlm.nih.gov/pubmed/33923548 http://dx.doi.org/10.3390/vaccines9040394 |
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