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Flagellin-Fused Protein Targeting M2e and HA2 Induces Innate and T-Cell Responses in Mice of Different Genetic Lines

Efficient control of influenza A infection can potentially be achieved through the development of broad-spectrum vaccines. Recombinant proteins incorporating conserved influenza A virus peptides are one of the platforms for the development of cross-protective influenza vaccines. We constructed a rec...

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Autores principales: Stepanova, Liudmila A., Shuklina, Marina A., Vasiliev, Kirill A., Kovaleva, Anna A., Vidyaeva, Inna G., Zabrodskaya, Yana A., Korotkov, Alexandr V., Tsybalova, Liudmila M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9786633/
https://www.ncbi.nlm.nih.gov/pubmed/36560509
http://dx.doi.org/10.3390/vaccines10122098
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author Stepanova, Liudmila A.
Shuklina, Marina A.
Vasiliev, Kirill A.
Kovaleva, Anna A.
Vidyaeva, Inna G.
Zabrodskaya, Yana A.
Korotkov, Alexandr V.
Tsybalova, Liudmila M.
author_facet Stepanova, Liudmila A.
Shuklina, Marina A.
Vasiliev, Kirill A.
Kovaleva, Anna A.
Vidyaeva, Inna G.
Zabrodskaya, Yana A.
Korotkov, Alexandr V.
Tsybalova, Liudmila M.
author_sort Stepanova, Liudmila A.
collection PubMed
description Efficient control of influenza A infection can potentially be achieved through the development of broad-spectrum vaccines. Recombinant proteins incorporating conserved influenza A virus peptides are one of the platforms for the development of cross-protective influenza vaccines. We constructed a recombinant protein Flg-HA2-2-4M2ehs, in which the extracellular domain of the M2 protein (M2e) and the sequence (aa76-130) of the second subunit of HA (HA2) were used as target antigens. In this study, we investigated the ability of the Flg-HA2-2-4M2ehs protein to activate innate immunity and stimulate the formation of T-cell response in mice of different genetic lines after intranasal immunization. Our studies showed that the Flg-HA2-2-4M2ehs protein was manifested in an increase in the relative content of neutrophils, monocytes, and interstitial macrophages, against the backdrop of a decrease in the level of dendritic cells and increased expression in the CD86 marker. In the lungs of BALB/c mice, immunization with the Flg-HA2-2-4M2ehs protein induced the formation of antigen-specific CD4+ and CD8+ effector memory T cells, producing TNF-α. In mice C57Bl/6, the formation of antigen-specific effector CD8+ T cells, predominantly producing IFN-γ+, was demonstrated. The data obtained showed the formation of CD8+ and CD4+ effector memory T cells expressing the CD107a.
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spelling pubmed-97866332022-12-24 Flagellin-Fused Protein Targeting M2e and HA2 Induces Innate and T-Cell Responses in Mice of Different Genetic Lines Stepanova, Liudmila A. Shuklina, Marina A. Vasiliev, Kirill A. Kovaleva, Anna A. Vidyaeva, Inna G. Zabrodskaya, Yana A. Korotkov, Alexandr V. Tsybalova, Liudmila M. Vaccines (Basel) Article Efficient control of influenza A infection can potentially be achieved through the development of broad-spectrum vaccines. Recombinant proteins incorporating conserved influenza A virus peptides are one of the platforms for the development of cross-protective influenza vaccines. We constructed a recombinant protein Flg-HA2-2-4M2ehs, in which the extracellular domain of the M2 protein (M2e) and the sequence (aa76-130) of the second subunit of HA (HA2) were used as target antigens. In this study, we investigated the ability of the Flg-HA2-2-4M2ehs protein to activate innate immunity and stimulate the formation of T-cell response in mice of different genetic lines after intranasal immunization. Our studies showed that the Flg-HA2-2-4M2ehs protein was manifested in an increase in the relative content of neutrophils, monocytes, and interstitial macrophages, against the backdrop of a decrease in the level of dendritic cells and increased expression in the CD86 marker. In the lungs of BALB/c mice, immunization with the Flg-HA2-2-4M2ehs protein induced the formation of antigen-specific CD4+ and CD8+ effector memory T cells, producing TNF-α. In mice C57Bl/6, the formation of antigen-specific effector CD8+ T cells, predominantly producing IFN-γ+, was demonstrated. The data obtained showed the formation of CD8+ and CD4+ effector memory T cells expressing the CD107a. MDPI 2022-12-08 /pmc/articles/PMC9786633/ /pubmed/36560509 http://dx.doi.org/10.3390/vaccines10122098 Text en © 2022 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
Stepanova, Liudmila A.
Shuklina, Marina A.
Vasiliev, Kirill A.
Kovaleva, Anna A.
Vidyaeva, Inna G.
Zabrodskaya, Yana A.
Korotkov, Alexandr V.
Tsybalova, Liudmila M.
Flagellin-Fused Protein Targeting M2e and HA2 Induces Innate and T-Cell Responses in Mice of Different Genetic Lines
title Flagellin-Fused Protein Targeting M2e and HA2 Induces Innate and T-Cell Responses in Mice of Different Genetic Lines
title_full Flagellin-Fused Protein Targeting M2e and HA2 Induces Innate and T-Cell Responses in Mice of Different Genetic Lines
title_fullStr Flagellin-Fused Protein Targeting M2e and HA2 Induces Innate and T-Cell Responses in Mice of Different Genetic Lines
title_full_unstemmed Flagellin-Fused Protein Targeting M2e and HA2 Induces Innate and T-Cell Responses in Mice of Different Genetic Lines
title_short Flagellin-Fused Protein Targeting M2e and HA2 Induces Innate and T-Cell Responses in Mice of Different Genetic Lines
title_sort flagellin-fused protein targeting m2e and ha2 induces innate and t-cell responses in mice of different genetic lines
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9786633/
https://www.ncbi.nlm.nih.gov/pubmed/36560509
http://dx.doi.org/10.3390/vaccines10122098
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