Efficacy of Intracellular Activated Promoters for Generation of Salmonella-Based Vaccines

DC FieldValueLanguage
dc.contributor.authorXu, Xin
dc.contributor.authorHusseiny, Mohamed I.
dc.contributor.authorGoldwich, Andreas
dc.contributor.authorHensel, Michael
dc.date.accessioned2021-12-23T16:18:12Z-
dc.date.available2021-12-23T16:18:12Z-
dc.date.issued2010
dc.identifier.issn00199567
dc.identifier.urihttps://osnascholar.ub.uni-osnabrueck.de/handle/unios/12580-
dc.description.abstractSalmonella enterica is a versatile vaccine carrier for heterologous antigens. One strategy for vaccine antigen delivery is the use of live attenuated S. enterica strains that translocate heterologous antigens into antigen-presenting cells by means of type III secretion systems (T3SS). The feasibility of this approach has been demonstrated in various experimental vaccination studies. The efficacy of recombinant live vaccines is critically influenced by the optimal level of attenuation and many other factors. For the rational design of approaches involving translocation by T3SS, additional parameters are the level of expression of the heterologous antigens and the selection of carrier proteins for the delivery of antigens to desirable subcellular compartments of the target cell. We deployed the Salmonella pathogenicity island 2 (SPI2)-encoded T3SS for antigen delivery. The SPI2-T3SS and effector proteins are encoded by members of the large SsrAB regulon, including promoters with highly variable strength of expression. We investigated the effect of various in vivo-activated promoters of the SsrAB regulon on the efficacy of recombinant Salmonella vaccines. We observed that the use of promoters with higher strength results in greater synthesis of recombinant antigens and greater stimulation of T-cell responses in cell culture assays for the stimulation of T cells by the model antigen ovalbumin. In contrast, in vaccination experiments, promoters with a low level of expression resulted in the induction of higher amounts of T cells reactive to the model antigen listeriolysin. These results demonstrate that high-level expression of heterologous antigens does not necessarily result in optimal stimulation of immune responses.
dc.description.sponsorshipDeutsche ForschungsgemeinschaftGerman Research Foundation (DFG) [SFB 796]; [HE 1964]; This study was supported by grant HE 1964 to M.H. and by grants with collaborative research center SFB 796 from the Deutsche Forschungsgemeinschaft.
dc.language.isoen
dc.publisherAMER SOC MICROBIOLOGY
dc.relation.ispartofINFECTION AND IMMUNITY
dc.subjectANTIGEN DELIVERY
dc.subjectCROSS-PRESENTATION
dc.subjectDENDRITIC CELLS
dc.subjectENTERICA
dc.subjectHOST-CELLS
dc.subjectIII SECRETION SYSTEM
dc.subjectImmunology
dc.subjectInfectious Diseases
dc.subjectPEPTIDES
dc.subjectRECOMBINANT VACCINES
dc.subjectSALMONELLA-PATHOGENICITY-ISLAND-2
dc.subjectTRANSLOCATED EFFECTORS
dc.titleEfficacy of Intracellular Activated Promoters for Generation of Salmonella-Based Vaccines
dc.typejournal article
dc.identifier.doi10.1128/IAI.00298-10
dc.identifier.isiISI:000283052100042
dc.description.volume78
dc.description.issue11
dc.description.startpage4828
dc.description.endpage4838
dc.contributor.orcid0000-0002-3470-2858
dc.contributor.orcid0000-0002-9485-8782
dc.publisher.place1752 N ST NW, WASHINGTON, DC 20036-2904 USA
dcterms.isPartOf.abbreviationInfect. Immun.
dcterms.oaStatusGreen Published, Bronze
crisitem.author.deptFB 05 - Biologie/Chemie-
crisitem.author.deptidfb05-
crisitem.author.orcid0000-0001-6604-6253-
crisitem.author.parentorgUniversität Osnabrück-
crisitem.author.netidHeMi480-
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