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Subcutaneous Immunization with Fusion Protein DnaJ-ΔA146Ply without Additional Adjuvants Induces both Humoral and Cellular Immunity against Pneumococcal Infection Partially Depending on TLR4

Subunit vaccines that are poorly immunogenic are often combined with adjuvants for immunization. Our previous research identified a pneumolysin variant (ΔA146Ply), a Toll-like receptor 4 agonist, that was an effective adjuvant in the protection of fusion protein DnaJ-ΔA146Ply against mucosal Strepto...

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Autores principales: Su, Yufeng, Li, Dagen, Xing, Yan, Wang, Hong, Wang, Jian, Yuan, Jun, Wang, Xiaofang, Cui, Fang, Yin, Yibing, Zhang, Xuemei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5466963/
https://www.ncbi.nlm.nih.gov/pubmed/28659923
http://dx.doi.org/10.3389/fimmu.2017.00686
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author Su, Yufeng
Li, Dagen
Xing, Yan
Wang, Hong
Wang, Jian
Yuan, Jun
Wang, Xiaofang
Cui, Fang
Yin, Yibing
Zhang, Xuemei
author_facet Su, Yufeng
Li, Dagen
Xing, Yan
Wang, Hong
Wang, Jian
Yuan, Jun
Wang, Xiaofang
Cui, Fang
Yin, Yibing
Zhang, Xuemei
author_sort Su, Yufeng
collection PubMed
description Subunit vaccines that are poorly immunogenic are often combined with adjuvants for immunization. Our previous research identified a pneumolysin variant (ΔA146Ply), a Toll-like receptor 4 agonist, that was an effective adjuvant in the protection of fusion protein DnaJ-ΔA146Ply against mucosal Streptococcus pneumoniae infections. For pneumococcal vaccines, World Health Organization recommend injection as a regular vaccination approach. Subcutaneous immunization is a common and effective method of injection, so we explored the immunity mechanism of subcutaneous immunization with DnaJ-ΔA146Ply. We found that mice immunized subcutaneously with fusion proteins ΔA146Ply-DnaJ and DnaJ-ΔA146Ply produced a higher anti-DnaJ IgG titer than when DnaJ alone was administered. DnaJ-ΔA146Ply induced both B-cell and T-cell-dependent protection against both colonization and lethal pneumococcal infections. Levels of IFN-γ, IL-4, and IL-17A were also elevated in DnaJ-ΔA146Ply immunized mice. However, all these effects were negated in TLR4(−/−) mice compared to WT mice immunized with DnaJ-ΔA146Ply. B-cell-deficient μMT mice, nude mice, IFN-γ(−/−), and IL-4(−/−) mice immunized with DnaJ-ΔA146Ply could not resist infection with pneumococci. IL-17A(−/−) and TLR4(−/−) mice did not benefit from DnaJ-ΔPly immunization in colonization experiments although their survival was not impaired compared with WT mice. Collectively, our data indicated that ΔA146Ply can be a potential subcutaneous adjuvant, and the DnaJ-ΔA146Ply fusion protein induces both humoral and cellular immune response to resist S. pneumoniae infection. The protective effect of colonization also depends on TLR4.
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spelling pubmed-54669632017-06-28 Subcutaneous Immunization with Fusion Protein DnaJ-ΔA146Ply without Additional Adjuvants Induces both Humoral and Cellular Immunity against Pneumococcal Infection Partially Depending on TLR4 Su, Yufeng Li, Dagen Xing, Yan Wang, Hong Wang, Jian Yuan, Jun Wang, Xiaofang Cui, Fang Yin, Yibing Zhang, Xuemei Front Immunol Immunology Subunit vaccines that are poorly immunogenic are often combined with adjuvants for immunization. Our previous research identified a pneumolysin variant (ΔA146Ply), a Toll-like receptor 4 agonist, that was an effective adjuvant in the protection of fusion protein DnaJ-ΔA146Ply against mucosal Streptococcus pneumoniae infections. For pneumococcal vaccines, World Health Organization recommend injection as a regular vaccination approach. Subcutaneous immunization is a common and effective method of injection, so we explored the immunity mechanism of subcutaneous immunization with DnaJ-ΔA146Ply. We found that mice immunized subcutaneously with fusion proteins ΔA146Ply-DnaJ and DnaJ-ΔA146Ply produced a higher anti-DnaJ IgG titer than when DnaJ alone was administered. DnaJ-ΔA146Ply induced both B-cell and T-cell-dependent protection against both colonization and lethal pneumococcal infections. Levels of IFN-γ, IL-4, and IL-17A were also elevated in DnaJ-ΔA146Ply immunized mice. However, all these effects were negated in TLR4(−/−) mice compared to WT mice immunized with DnaJ-ΔA146Ply. B-cell-deficient μMT mice, nude mice, IFN-γ(−/−), and IL-4(−/−) mice immunized with DnaJ-ΔA146Ply could not resist infection with pneumococci. IL-17A(−/−) and TLR4(−/−) mice did not benefit from DnaJ-ΔPly immunization in colonization experiments although their survival was not impaired compared with WT mice. Collectively, our data indicated that ΔA146Ply can be a potential subcutaneous adjuvant, and the DnaJ-ΔA146Ply fusion protein induces both humoral and cellular immune response to resist S. pneumoniae infection. The protective effect of colonization also depends on TLR4. Frontiers Media S.A. 2017-06-12 /pmc/articles/PMC5466963/ /pubmed/28659923 http://dx.doi.org/10.3389/fimmu.2017.00686 Text en Copyright © 2017 Su, Li, Xing, Wang, Wang, Yuan, Wang, Cui, Yin and Zhang. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Su, Yufeng
Li, Dagen
Xing, Yan
Wang, Hong
Wang, Jian
Yuan, Jun
Wang, Xiaofang
Cui, Fang
Yin, Yibing
Zhang, Xuemei
Subcutaneous Immunization with Fusion Protein DnaJ-ΔA146Ply without Additional Adjuvants Induces both Humoral and Cellular Immunity against Pneumococcal Infection Partially Depending on TLR4
title Subcutaneous Immunization with Fusion Protein DnaJ-ΔA146Ply without Additional Adjuvants Induces both Humoral and Cellular Immunity against Pneumococcal Infection Partially Depending on TLR4
title_full Subcutaneous Immunization with Fusion Protein DnaJ-ΔA146Ply without Additional Adjuvants Induces both Humoral and Cellular Immunity against Pneumococcal Infection Partially Depending on TLR4
title_fullStr Subcutaneous Immunization with Fusion Protein DnaJ-ΔA146Ply without Additional Adjuvants Induces both Humoral and Cellular Immunity against Pneumococcal Infection Partially Depending on TLR4
title_full_unstemmed Subcutaneous Immunization with Fusion Protein DnaJ-ΔA146Ply without Additional Adjuvants Induces both Humoral and Cellular Immunity against Pneumococcal Infection Partially Depending on TLR4
title_short Subcutaneous Immunization with Fusion Protein DnaJ-ΔA146Ply without Additional Adjuvants Induces both Humoral and Cellular Immunity against Pneumococcal Infection Partially Depending on TLR4
title_sort subcutaneous immunization with fusion protein dnaj-δa146ply without additional adjuvants induces both humoral and cellular immunity against pneumococcal infection partially depending on tlr4
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5466963/
https://www.ncbi.nlm.nih.gov/pubmed/28659923
http://dx.doi.org/10.3389/fimmu.2017.00686
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