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Comparative immunological evaluation of recombinant Salmonella Typhimurium strains expressing model antigens as live oral vaccines.
- Source :
-
BMC immunology [BMC Immunol] 2012 Sep 26; Vol. 13, pp. 54. Date of Electronic Publication: 2012 Sep 26. - Publication Year :
- 2012
-
Abstract
- 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.<br />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.<br />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.
- Subjects :
- Administration, Oral
Animals
Anti-Bacterial Agents pharmacology
Female
Green Fluorescent Proteins metabolism
Hemagglutination Inhibition Tests
Immunity, Humoral drug effects
Immunity, Humoral immunology
Influenza A Virus, H5N1 Subtype immunology
Interferon-gamma immunology
Mice
Mice, Inbred BALB C
Microbial Viability drug effects
Plasmids genetics
Salmonella Infections, Animal immunology
Salmonella Infections, Animal microbiology
Salmonella Vaccines administration & dosage
Salmonella typhimurium cytology
Salmonella typhimurium drug effects
Salmonella typhimurium growth & development
Antigens, Bacterial immunology
Hemagglutinin Glycoproteins, Influenza Virus immunology
Recombination, Genetic genetics
Salmonella Vaccines immunology
Salmonella typhimurium immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1471-2172
- Volume :
- 13
- Database :
- MEDLINE
- Journal :
- BMC immunology
- Publication Type :
- Academic Journal
- Accession number :
- 23013063
- Full Text :
- https://doi.org/10.1186/1471-2172-13-54