Enhancement of the Local CD8<sup>+</sup> T-Cellular Immune Response to <i>Mycobacterium tuberculosis</i> in BCG-Primed Mice after Intranasal Administration of Influenza Vector Vaccine Carrying TB10.4 and HspX Antigens

Enhancement of the Local CD8<sup>+</sup> T-Cellular Immune Response to <i>Mycobacterium tuberculosis</i> in BCG-Primed Mice after Intranasal Administration of Influenza Vector Vaccine Carrying TB10.4 and HspX Antigens

BCG is the only licensed vaccine against <i>Mycobacterium tuberculosis (M.tb)</i> infection. Due to its intramuscular administration route, BCG is unable to induce a local protective immune response in the respiratory system. Moreover, BCG has a diminished ability to induce long-lived me...

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Autores principales: Kirill Vasilyev, Anna-Polina Shurygina, Natalia Zabolotnykh, Mariia Sergeeva, Ekaterina Romanovskaya-Romanko, Anastasia Pulkina, Janna Buzitskaya, Marine Z. Dogonadze, Tatiana I. Vinogradova, Marina A. Stukova
Formato: article
Lenguaje:EN
Publicado: MDPI AG 2021
Materias:
<i>M. tuberculosis</i> vaccine
TB10.4
HspX
influenza vector
mucosal immunization
innate immune response
Medicine
R
Acceso en línea:https://doaj.org/article/0834a9890ac0450ea8bb455b9f114e17
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spelling oai:doaj.org-article:0834a9890ac0450ea8bb455b9f114e172021-11-25T19:10:50ZEnhancement of the Local CD8<sup>+</sup> T-Cellular Immune Response to <i>Mycobacterium tuberculosis</i> in BCG-Primed Mice after Intranasal Administration of Influenza Vector Vaccine Carrying TB10.4 and HspX Antigens10.3390/vaccines91112732076-393Xhttps://doaj.org/article/0834a9890ac0450ea8bb455b9f114e172021-11-01T00:00:00Zhttps://www.mdpi.com/2076-393X/9/11/1273https://doaj.org/toc/2076-393XBCG is the only licensed vaccine against <i>Mycobacterium tuberculosis (M.tb)</i> infection. Due to its intramuscular administration route, BCG is unable to induce a local protective immune response in the respiratory system. Moreover, BCG has a diminished ability to induce long-lived memory T-cells which are indispensable for antituberculosis protection. Recently we described the protective efficacy of new mucosal TB vaccine candidate based on recombinant attenuated influenza vector (Flu/THSP) co-expressing TB10.4 and HspX proteins of <i>M.tb</i> within an NS1 influenza protein open reading frame. In the present work, the innate and adaptive immune response to immunization with the Flu/THSP and the immunological properties of vaccine candidate in the BCG-prime → Flu/THSP vector boost vaccination scheme are studied in mice. It was shown that the mucosal administration of Flu/THSP induces the incoming of interstitial macrophages in the lung tissue and stimulates the expression of co-stimulatory CD86 and CD83 molecules on antigen-presenting cells. The T-cellular immune response to Flu/THSP vector was mediated predominantly by the IFNγ-producing CD8<sup>+</sup> lymphocytes. BCG-prime → Flu/THSP vector boost immunization scheme was shown to protect mice from severe lung injury caused by <i>M.tb</i> infection due to the enhanced T-cellular immune response, mediated by antigen-specific effector and central memory CD4<sup>+</sup> and CD8<sup>+</sup> T-lymphocytes.Kirill VasilyevAnna-Polina ShuryginaNatalia ZabolotnykhMariia SergeevaEkaterina Romanovskaya-RomankoAnastasia PulkinaJanna BuzitskayaMarine Z. DogonadzeTatiana I. VinogradovaMarina A. StukovaMDPI AGarticle<i>M. tuberculosis</i> vaccineTB10.4HspXinfluenza vectormucosal immunizationinnate immune responseMedicineRENVaccines, Vol 9, Iss 1273, p 1273 (2021)
institution DOAJ
collection DOAJ
language EN
topic <i>M. tuberculosis</i> vaccine
TB10.4
HspX
influenza vector
mucosal immunization
innate immune response
Medicine
R
spellingShingle <i>M. tuberculosis</i> vaccine
TB10.4
HspX
influenza vector
mucosal immunization
innate immune response
Medicine
R
Kirill Vasilyev
Anna-Polina Shurygina
Natalia Zabolotnykh
Mariia Sergeeva
Ekaterina Romanovskaya-Romanko
Anastasia Pulkina
Janna Buzitskaya
Marine Z. Dogonadze
Tatiana I. Vinogradova
Marina A. Stukova
Enhancement of the Local CD8<sup>+</sup> T-Cellular Immune Response to <i>Mycobacterium tuberculosis</i> in BCG-Primed Mice after Intranasal Administration of Influenza Vector Vaccine Carrying TB10.4 and HspX Antigens
description BCG is the only licensed vaccine against <i>Mycobacterium tuberculosis (M.tb)</i> infection. Due to its intramuscular administration route, BCG is unable to induce a local protective immune response in the respiratory system. Moreover, BCG has a diminished ability to induce long-lived memory T-cells which are indispensable for antituberculosis protection. Recently we described the protective efficacy of new mucosal TB vaccine candidate based on recombinant attenuated influenza vector (Flu/THSP) co-expressing TB10.4 and HspX proteins of <i>M.tb</i> within an NS1 influenza protein open reading frame. In the present work, the innate and adaptive immune response to immunization with the Flu/THSP and the immunological properties of vaccine candidate in the BCG-prime → Flu/THSP vector boost vaccination scheme are studied in mice. It was shown that the mucosal administration of Flu/THSP induces the incoming of interstitial macrophages in the lung tissue and stimulates the expression of co-stimulatory CD86 and CD83 molecules on antigen-presenting cells. The T-cellular immune response to Flu/THSP vector was mediated predominantly by the IFNγ-producing CD8<sup>+</sup> lymphocytes. BCG-prime → Flu/THSP vector boost immunization scheme was shown to protect mice from severe lung injury caused by <i>M.tb</i> infection due to the enhanced T-cellular immune response, mediated by antigen-specific effector and central memory CD4<sup>+</sup> and CD8<sup>+</sup> T-lymphocytes.
format article
author Kirill Vasilyev
Anna-Polina Shurygina
Natalia Zabolotnykh
Mariia Sergeeva
Ekaterina Romanovskaya-Romanko
Anastasia Pulkina
Janna Buzitskaya
Marine Z. Dogonadze
Tatiana I. Vinogradova
Marina A. Stukova
author_facet Kirill Vasilyev
Anna-Polina Shurygina
Natalia Zabolotnykh
Mariia Sergeeva
Ekaterina Romanovskaya-Romanko
Anastasia Pulkina
Janna Buzitskaya
Marine Z. Dogonadze
Tatiana I. Vinogradova
Marina A. Stukova
author_sort Kirill Vasilyev
title Enhancement of the Local CD8<sup>+</sup> T-Cellular Immune Response to <i>Mycobacterium tuberculosis</i> in BCG-Primed Mice after Intranasal Administration of Influenza Vector Vaccine Carrying TB10.4 and HspX Antigens
title_short Enhancement of the Local CD8<sup>+</sup> T-Cellular Immune Response to <i>Mycobacterium tuberculosis</i> in BCG-Primed Mice after Intranasal Administration of Influenza Vector Vaccine Carrying TB10.4 and HspX Antigens
title_full Enhancement of the Local CD8<sup>+</sup> T-Cellular Immune Response to <i>Mycobacterium tuberculosis</i> in BCG-Primed Mice after Intranasal Administration of Influenza Vector Vaccine Carrying TB10.4 and HspX Antigens
title_fullStr Enhancement of the Local CD8<sup>+</sup> T-Cellular Immune Response to <i>Mycobacterium tuberculosis</i> in BCG-Primed Mice after Intranasal Administration of Influenza Vector Vaccine Carrying TB10.4 and HspX Antigens
title_full_unstemmed Enhancement of the Local CD8<sup>+</sup> T-Cellular Immune Response to <i>Mycobacterium tuberculosis</i> in BCG-Primed Mice after Intranasal Administration of Influenza Vector Vaccine Carrying TB10.4 and HspX Antigens
title_sort enhancement of the local cd8<sup>+</sup> t-cellular immune response to <i>mycobacterium tuberculosis</i> in bcg-primed mice after intranasal administration of influenza vector vaccine carrying tb10.4 and hspx antigens
publisher MDPI AG
publishDate 2021
url https://doaj.org/article/0834a9890ac0450ea8bb455b9f114e17
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