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Comparative immunological evaluation of recombinant Salmonella Typhimurium strains expressing model antigens as live oral vaccines

BACKGROUND: Despite the development of various systems to generate live recombinant Salmonella Typhimurium vaccine strains, little work has been performed to systematically evaluate and compare their relative immunogenicity. Such information would provide invaluable guidance for the future rational...

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Autores principales: Zheng, Song-yue, Yu, Bin, Zhang, Ke, Chen, Min, Hua, Yan-Hong, Yuan, Shuofeng, Watt, Rory M, Zheng, Bo-Jian, Yuen, Kwok-Yung, Huang, Jian-Dong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3503649/
https://www.ncbi.nlm.nih.gov/pubmed/23013063
http://dx.doi.org/10.1186/1471-2172-13-54
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author Zheng, Song-yue
Yu, Bin
Zhang, Ke
Chen, Min
Hua, Yan-Hong
Yuan, Shuofeng
Watt, Rory M
Zheng, Bo-Jian
Yuen, Kwok-Yung
Huang, Jian-Dong
author_facet Zheng, Song-yue
Yu, Bin
Zhang, Ke
Chen, Min
Hua, Yan-Hong
Yuan, Shuofeng
Watt, Rory M
Zheng, Bo-Jian
Yuen, Kwok-Yung
Huang, Jian-Dong
author_sort Zheng, Song-yue
collection PubMed
description BACKGROUND: Despite the development of various systems to generate live recombinant Salmonella Typhimurium vaccine strains, little work has been performed to systematically evaluate and compare their relative immunogenicity. Such information would provide invaluable guidance for the future rational design of live recombinant Salmonella oral vaccines. RESULT: To compare vaccine strains encoded with different antigen delivery and expression strategies, a series of recombinant Salmonella Typhimurium strains were constructed that expressed either the enhanced green fluorescent protein (EGFP) or a fragment of the hemagglutinin (HA) protein from the H5N1 influenza virus, as model antigens. The antigens were expressed from the chromosome, from high or low-copy plasmids, or encoded on a eukaryotic expression plasmid. Antigens were targeted for expression in either the cytoplasm or the outer membrane. Combinations of strategies were employed to evaluate the efficacy of combined delivery/expression approaches. After investigating in vitro and in vivo antigen expression, growth and infection abilities; the immunogenicity of the constructed recombinant Salmonella strains was evaluated in mice. Using the soluble model antigen EGFP, our results indicated that vaccine strains with high and stable antigen expression exhibited high B cell responses, whilst eukaryotic expression or colonization with good construct stability was critical for T cell responses. For the insoluble model antigen HA, an outer membrane expression strategy induced better B cell and T cell responses than a cytoplasmic strategy. Most notably, the combination of two different expression strategies did not increase the immune response elicited. CONCLUSION: Through systematically evaluating and comparing the immunogenicity of the constructed recombinant Salmonella strains in mice, we identified their respective advantages and deleterious or synergistic effects. Different construction strategies were optimally-required for soluble versus insoluble forms of the protein antigens. If an antigen, such as EGFP, is soluble and expressed at high levels, a low-copy plasmid-cytoplasmic expression strategy is recommended; since it provokes the highest B cell responses and also induces good T cell responses. If a T cell response is preferred, a eukaryotic expression plasmid or a chromosome-based, cytoplasmic-expression strategy is more effective. For insoluble antigens such as HA, an outer membrane expression strategy is recommended.
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spelling pubmed-35036492012-11-22 Comparative immunological evaluation of recombinant Salmonella Typhimurium strains expressing model antigens as live oral vaccines Zheng, Song-yue Yu, Bin Zhang, Ke Chen, Min Hua, Yan-Hong Yuan, Shuofeng Watt, Rory M Zheng, Bo-Jian Yuen, Kwok-Yung Huang, Jian-Dong BMC Immunol Research Article BACKGROUND: Despite the development of various systems to generate live recombinant Salmonella Typhimurium vaccine strains, little work has been performed to systematically evaluate and compare their relative immunogenicity. Such information would provide invaluable guidance for the future rational design of live recombinant Salmonella oral vaccines. RESULT: To compare vaccine strains encoded with different antigen delivery and expression strategies, a series of recombinant Salmonella Typhimurium strains were constructed that expressed either the enhanced green fluorescent protein (EGFP) or a fragment of the hemagglutinin (HA) protein from the H5N1 influenza virus, as model antigens. The antigens were expressed from the chromosome, from high or low-copy plasmids, or encoded on a eukaryotic expression plasmid. Antigens were targeted for expression in either the cytoplasm or the outer membrane. Combinations of strategies were employed to evaluate the efficacy of combined delivery/expression approaches. After investigating in vitro and in vivo antigen expression, growth and infection abilities; the immunogenicity of the constructed recombinant Salmonella strains was evaluated in mice. Using the soluble model antigen EGFP, our results indicated that vaccine strains with high and stable antigen expression exhibited high B cell responses, whilst eukaryotic expression or colonization with good construct stability was critical for T cell responses. For the insoluble model antigen HA, an outer membrane expression strategy induced better B cell and T cell responses than a cytoplasmic strategy. Most notably, the combination of two different expression strategies did not increase the immune response elicited. CONCLUSION: Through systematically evaluating and comparing the immunogenicity of the constructed recombinant Salmonella strains in mice, we identified their respective advantages and deleterious or synergistic effects. Different construction strategies were optimally-required for soluble versus insoluble forms of the protein antigens. If an antigen, such as EGFP, is soluble and expressed at high levels, a low-copy plasmid-cytoplasmic expression strategy is recommended; since it provokes the highest B cell responses and also induces good T cell responses. If a T cell response is preferred, a eukaryotic expression plasmid or a chromosome-based, cytoplasmic-expression strategy is more effective. For insoluble antigens such as HA, an outer membrane expression strategy is recommended. BioMed Central 2012-09-26 /pmc/articles/PMC3503649/ /pubmed/23013063 http://dx.doi.org/10.1186/1471-2172-13-54 Text en Copyright ©2012 Zheng et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Zheng, Song-yue
Yu, Bin
Zhang, Ke
Chen, Min
Hua, Yan-Hong
Yuan, Shuofeng
Watt, Rory M
Zheng, Bo-Jian
Yuen, Kwok-Yung
Huang, Jian-Dong
Comparative immunological evaluation of recombinant Salmonella Typhimurium strains expressing model antigens as live oral vaccines
title Comparative immunological evaluation of recombinant Salmonella Typhimurium strains expressing model antigens as live oral vaccines
title_full Comparative immunological evaluation of recombinant Salmonella Typhimurium strains expressing model antigens as live oral vaccines
title_fullStr Comparative immunological evaluation of recombinant Salmonella Typhimurium strains expressing model antigens as live oral vaccines
title_full_unstemmed Comparative immunological evaluation of recombinant Salmonella Typhimurium strains expressing model antigens as live oral vaccines
title_short Comparative immunological evaluation of recombinant Salmonella Typhimurium strains expressing model antigens as live oral vaccines
title_sort comparative immunological evaluation of recombinant salmonella typhimurium strains expressing model antigens as live oral vaccines
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3503649/
https://www.ncbi.nlm.nih.gov/pubmed/23013063
http://dx.doi.org/10.1186/1471-2172-13-54
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