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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...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2012
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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. |
format | Online Article Text |
id | pubmed-3503649 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
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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