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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...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
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.
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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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