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

TitleComparative immunological evaluation of recombinant Salmonella Typhimurium strains expressing model antigens as live oral vaccines
Authors
KeywordsSalmonella Typhimurium
Live oral vaccine
Soluble and insoluble antigens
Construction strategies
Immunological comparison
Issue Date2012
PublisherBioMed Central Ltd. The Journal's web site is located at http://www.biomedcentral.com/bmcimmunol/
Citation
BMC Immunology, 2012, v. 13, article no. 54 How to Cite?
AbstractBackground: 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.
Persistent Identifierhttp://hdl.handle.net/10722/185641
ISSN
2017 Impact Factor: 2.615
2015 SCImago Journal Rankings: 1.087
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorZheng, S-
dc.contributor.authorYu, B-
dc.contributor.authorZhang, K-
dc.contributor.authorChen, M-
dc.contributor.authorHua, Y-
dc.contributor.authorYuan, S-
dc.contributor.authorWatt, RM-
dc.contributor.authorZheng, B-
dc.contributor.authorYuen, KY-
dc.contributor.authorHuang, J-
dc.date.accessioned2013-08-20T11:36:15Z-
dc.date.available2013-08-20T11:36:15Z-
dc.date.issued2012-
dc.identifier.citationBMC Immunology, 2012, v. 13, article no. 54-
dc.identifier.issn1471-2172-
dc.identifier.urihttp://hdl.handle.net/10722/185641-
dc.description.abstractBackground: 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.-
dc.languageeng-
dc.publisherBioMed Central Ltd. The Journal's web site is located at http://www.biomedcentral.com/bmcimmunol/-
dc.relation.ispartofBMC Immunology-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectSalmonella Typhimurium-
dc.subjectLive oral vaccine-
dc.subjectSoluble and insoluble antigens-
dc.subjectConstruction strategies-
dc.subjectImmunological comparison-
dc.titleComparative immunological evaluation of recombinant Salmonella Typhimurium strains expressing model antigens as live oral vaccines-
dc.typeArticle-
dc.identifier.emailChen, M: jiange@hkucc.hku.hk-
dc.identifier.emailYuan, S: yuansf@hku.hk-
dc.identifier.emailWatt, RM: rmwatt@hku.hk-
dc.identifier.emailZheng, B: bzheng@hkucc.hku.hk-
dc.identifier.emailYuen, KY: kyyuen@hkucc.hku.hk-
dc.identifier.emailHuang, J: jdhuang@hku.hk-
dc.identifier.authorityYuan, S=rp02640-
dc.identifier.authorityWatt, RM=rp00043-
dc.identifier.authorityZheng, B=rp00353-
dc.identifier.authorityYuen, KY=rp00366-
dc.identifier.authorityHuang, J=rp00451-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1186/1471-2172-13-54-
dc.identifier.pmid23013063-
dc.identifier.pmcidPMC3503649-
dc.identifier.scopuseid_2-s2.0-84866550685-
dc.identifier.hkuros220023-
dc.identifier.volume13-
dc.identifier.spagearticle no. 54-
dc.identifier.epagearticle no. 54-
dc.identifier.isiWOS:000311354400001-
dc.publisher.placeUnited Kingdom-
dc.identifier.issnl1471-2172-

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