Autodisplay: Development of an Efficacious System for Surface Display of Antigenic Determinants in<i>Salmonella</i>Vaccine Strains

Kramer, Uwe; Rizos, Konstantin; Apfel, Heiko; Autenrieth, Ingo B.; Lattemann, Claus T.

doi:10.1128/iai.71.4.1944-1952.2003

Cited by 38 publications

(32 citation statements)

References 47 publications

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“…For the in vivo experiments transcriptional fusions of AIDA-I and UreA were first constructed in plasmid pLAT238. Plasmid pLAT238 encodes the epitope tag PEYFK derived from the Nef protein from the human immunodeficiency virus fused to a modified cholera toxin B subunit (CTB) gene, followed by the sequence encoding the autotransporter domain of AIDA-I, and it contains a single BglII restriction site between the Nef tag and the signal peptide sequence of CTB (30). Expression of the fusion in pLAT238 is transcriptionally controlled by the constitutive P TK promoter (25).…”

Section: Methodsmentioning

confidence: 99%

“…Recently, we observed that an attenuated Salmonella vaccine strain expressing a CD4 ϩ T-cell epitope on its surface via the autotransporter domain of AIDA-I (an adhesin involved in diffuse adherence from Escherichia coli [3]) was able to induce a specific CD4 ϩ T-cell response (30). These findings encouraged us to investigate whether the AIDA-I expression system is able to induce protective immune responses in an animal model of infectious disease in which protection is mainly mediated by CD4 ϩ T cells.…”

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confidence: 99%

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Autodisplay

et al. 2003

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Live attenuated Salmonella strains expressing antigens of pathogens are promising oral vaccine candidates. There is growing evidence that the topology of expression of the foreign antigens can have a dramatic impact on the immunogenicity. We examined the potential of the AIDA-I (Escherichia coli adhesin involved in diffuse adherence) autotransporter domain to display antigenic fragments of the urease A subunit of Helicobacter pylori for the induction of a protective immune response. In the murine H. pylori model, protection is mainly mediated by CD4؉ T cells, and we therefore used the AIDA-I expression system to successfully express both nearly full-length UreA and defined T-helper-cell epitopes on the surface of an attenuated Salmonella enterica serovar Typhimurium vaccine strain. Surface exposure of the large UreA fragment or of one UreA T-cell epitope mediated a significant reduction in the level of H. pylori in immunized mice after challenge infection, whereas conventional cytoplasmic expression of UreA in Salmonella had no effect. These results support the concept that surface display increases the immunogenicity of recombinant antigens expressed on oral live vaccine carriers and further demonstrate the feasibility of immunizing against H. pylori with Salmonella vaccine strains expressing CD4؉ T-cell epitopes.

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Section: Methodsmentioning

confidence: 99%

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confidence: 99%

Autodisplay

et al. 2003

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“…The seminal work on secretion has also demonstrated the potential biotechnological exploitation of the autotransporter secretion pathway, namely, by displaying heterologous proteins on the bacterial surface (453). The possible applications of this autodisplay system are numerous and include (i) exposure of antigenic determinants for vaccine development (142,267,316), (ii) expression of peptide libraries for epitope mapping or antibody specificity test (258), (iii) display of receptor or ligand for binding assays or purification (499,500), (iv) functional domain analyses of a heterologous protein (59,499,500), and (v) bioconversion by expressing enzymatic activity on the bacterial surface (229,230,276). In conclusion, further understanding of the autotransporter secretion pathway and the functions of the passenger domains will facilitate a richer view of the mechanisms and evolution of bacterial pathogenesis and provide important practical applications for the medical and biotechnological communities.…”

Section: Future Directionsmentioning

confidence: 99%

Type V Protein Secretion Pathway: the Autotransporter Story

Henderson

Navarro-Garcı́a

Desvaux

et al. 2004

Microbiol Mol Biol Rev

713

795

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Gram-negative bacteria possess an outer membrane layer which constrains uptake and secretion of solutes and polypeptides. To overcome this barrier, bacteria have developed several systems for protein secretion. The type V secretion pathway encompasses the autotransporter proteins, the two-partner secretion system, and the recently described type Vc or AT-2 family of proteins. Since its discovery in the late 1980s, this family of secreted proteins has expanded continuously, due largely to the advent of the genomic age, to become the largest group of secreted proteins in gram-negative bacteria. Several of these proteins play essential roles in the pathogenesis of bacterial infections and have been characterized in detail, demonstrating a diverse array of function including the ability to condense host cell actin and to modulate apoptosis. However, most of the autotransporter proteins remain to be characterized. In light of new discoveries and controversies in this research field, this review considers the autotransporter secretion process in the context of the more general field of bacterial protein translocation and exoprotein function

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“…The autotransporter secretion pathway of gram-negative bacteria has been used for the surface display of antigenic determinants (81). Autotransporters are expressed as a single polypeptide chain containing all of the features necessary to translocate an N-terminal passenger domain to the cell surface, which makes them attractive candidates for antigen display.…”

Section: Location Location Locationmentioning

confidence: 99%