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Preclinical Evaluation of TB/FLU-04L—An Intranasal Influenza Vector-Based Boost Vaccine against Tuberculosis

Tuberculosis is a major global threat to human health. Since the widely used BCG vaccine is poorly effective in adults, there is a demand for the development of a new type of boost tuberculosis vaccine. We designed a novel intranasal tuberculosis vaccine candidate, TB/FLU-04L, which is based on an a...

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Autores principales: Shurygina, Anna-Polina, Zabolotnykh, Natalia, Vinogradova, Tatiana, Khairullin, Berik, Kassenov, Markhabat, Nurpeisova, Ainur, Sarsenbayeva, Gulbanu, Sansyzbay, Abylai, Vasilyev, Kirill, Buzitskaya, Janna, Egorov, Andrey, Stukova, Marina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10138401/
https://www.ncbi.nlm.nih.gov/pubmed/37108602
http://dx.doi.org/10.3390/ijms24087439
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author Shurygina, Anna-Polina
Zabolotnykh, Natalia
Vinogradova, Tatiana
Khairullin, Berik
Kassenov, Markhabat
Nurpeisova, Ainur
Sarsenbayeva, Gulbanu
Sansyzbay, Abylai
Vasilyev, Kirill
Buzitskaya, Janna
Egorov, Andrey
Stukova, Marina
author_facet Shurygina, Anna-Polina
Zabolotnykh, Natalia
Vinogradova, Tatiana
Khairullin, Berik
Kassenov, Markhabat
Nurpeisova, Ainur
Sarsenbayeva, Gulbanu
Sansyzbay, Abylai
Vasilyev, Kirill
Buzitskaya, Janna
Egorov, Andrey
Stukova, Marina
author_sort Shurygina, Anna-Polina
collection PubMed
description Tuberculosis is a major global threat to human health. Since the widely used BCG vaccine is poorly effective in adults, there is a demand for the development of a new type of boost tuberculosis vaccine. We designed a novel intranasal tuberculosis vaccine candidate, TB/FLU-04L, which is based on an attenuated influenza A virus vector encoding two mycobacterium antigens, Ag85A and ESAT-6. As tuberculosis is an airborne disease, the ability to induce mucosal immunity is one of the potential advantages of influenza vectors. Sequences of ESAT-6 and Ag85A antigens were inserted into the NS1 open reading frame of the influenza A virus to replace the deleted carboxyl part of the NS1 protein. The vector expressing chimeric NS1 protein appeared to be genetically stable and replication-deficient in mice and non-human primates. Intranasal immunization of C57BL/6 mice or cynomolgus macaques with the TB/FLU-04L vaccine candidate induced Mtb-specific Th1 immune response. Single TB/FLU-04L immunization in mice showed commensurate levels of protection in comparison to BCG and significantly increased the protective effect of BCG when applied in a “prime-boost” scheme. Our findings show that intranasal immunization with the TB/FLU-04L vaccine, which carries two mycobacterium antigens, is safe, and induces a protective immune response against virulent M. tuberculosis.
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spelling pubmed-101384012023-04-28 Preclinical Evaluation of TB/FLU-04L—An Intranasal Influenza Vector-Based Boost Vaccine against Tuberculosis Shurygina, Anna-Polina Zabolotnykh, Natalia Vinogradova, Tatiana Khairullin, Berik Kassenov, Markhabat Nurpeisova, Ainur Sarsenbayeva, Gulbanu Sansyzbay, Abylai Vasilyev, Kirill Buzitskaya, Janna Egorov, Andrey Stukova, Marina Int J Mol Sci Article Tuberculosis is a major global threat to human health. Since the widely used BCG vaccine is poorly effective in adults, there is a demand for the development of a new type of boost tuberculosis vaccine. We designed a novel intranasal tuberculosis vaccine candidate, TB/FLU-04L, which is based on an attenuated influenza A virus vector encoding two mycobacterium antigens, Ag85A and ESAT-6. As tuberculosis is an airborne disease, the ability to induce mucosal immunity is one of the potential advantages of influenza vectors. Sequences of ESAT-6 and Ag85A antigens were inserted into the NS1 open reading frame of the influenza A virus to replace the deleted carboxyl part of the NS1 protein. The vector expressing chimeric NS1 protein appeared to be genetically stable and replication-deficient in mice and non-human primates. Intranasal immunization of C57BL/6 mice or cynomolgus macaques with the TB/FLU-04L vaccine candidate induced Mtb-specific Th1 immune response. Single TB/FLU-04L immunization in mice showed commensurate levels of protection in comparison to BCG and significantly increased the protective effect of BCG when applied in a “prime-boost” scheme. Our findings show that intranasal immunization with the TB/FLU-04L vaccine, which carries two mycobacterium antigens, is safe, and induces a protective immune response against virulent M. tuberculosis. MDPI 2023-04-18 /pmc/articles/PMC10138401/ /pubmed/37108602 http://dx.doi.org/10.3390/ijms24087439 Text en © 2023 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
Shurygina, Anna-Polina
Zabolotnykh, Natalia
Vinogradova, Tatiana
Khairullin, Berik
Kassenov, Markhabat
Nurpeisova, Ainur
Sarsenbayeva, Gulbanu
Sansyzbay, Abylai
Vasilyev, Kirill
Buzitskaya, Janna
Egorov, Andrey
Stukova, Marina
Preclinical Evaluation of TB/FLU-04L—An Intranasal Influenza Vector-Based Boost Vaccine against Tuberculosis
title Preclinical Evaluation of TB/FLU-04L—An Intranasal Influenza Vector-Based Boost Vaccine against Tuberculosis
title_full Preclinical Evaluation of TB/FLU-04L—An Intranasal Influenza Vector-Based Boost Vaccine against Tuberculosis
title_fullStr Preclinical Evaluation of TB/FLU-04L—An Intranasal Influenza Vector-Based Boost Vaccine against Tuberculosis
title_full_unstemmed Preclinical Evaluation of TB/FLU-04L—An Intranasal Influenza Vector-Based Boost Vaccine against Tuberculosis
title_short Preclinical Evaluation of TB/FLU-04L—An Intranasal Influenza Vector-Based Boost Vaccine against Tuberculosis
title_sort preclinical evaluation of tb/flu-04l—an intranasal influenza vector-based boost vaccine against tuberculosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10138401/
https://www.ncbi.nlm.nih.gov/pubmed/37108602
http://dx.doi.org/10.3390/ijms24087439
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