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dc.contributor.authorSelke, Martin
dc.contributor.authorMeens, Jochen
dc.contributor.authorSpringer, Sven
dc.contributor.authorFrank, Ronald
dc.contributor.authorGerlach, Gerald-F
dc.date.accessioned2017-01-20T12:15:59Z
dc.date.available2017-01-20T12:15:59Z
dc.date.issued2007-05
dc.identifier.citationImmunization of pigs to prevent disease in humans: construction and protective efficacy of a Salmonella enterica serovar Typhimurium live negative-marker vaccine. 2007, 75 (5):2476-83 Infect. Immun.en
dc.identifier.issn0019-9567
dc.identifier.pmid17296750
dc.identifier.doi10.1128/IAI.01908-06
dc.identifier.urihttp://hdl.handle.net/10033/620735
dc.description.abstractZoonotic infections caused by Salmonella enterica serovar Typhimurium pose a constant threat to consumer health, with the pig being a particularly major source of multidrug-resistant isolates. Vaccination, as a promising approach to reduce colonization and shedding, has been scarcely used, as it interferes with current control programs relying on serology as a means of herd classification. In order to overcome this problem, we set out to develop a negative-marker vaccine allowing the differentiation of infected from vaccinated animals (DIVA). Applying an immunoproteomic approach with two-dimensional gel electrophoresis, Western blot, and quadrupole time-of-flight tandem mass spectrometry, we identified the OmpD protein as a suitable negative marker. Using allelic exchange, we generated an isogenic mutant of the licensed live vaccine strain Salmoporc and showed that virulence of Salmoporc and that of the mutant strain, SalmoporcDeltaompD, were indistinguishable in BALB/c mice. In a pig infection experiment including two oral immunizations with SalmoporcDeltaompD and challenge with a multiresistant S. enterica serovar Typhimurium DT104 clinical isolate, we confirmed the protective efficacy of SalmoporcDeltaompD in pigs, showing a significant reduction of both clinical symptoms and colonization of lymph nodes and intestinal tract. OmpD immunogenic epitopes were determined by peptide spot array analyses. Upon testing of several 9-mer peptides, each including an immunogenic epitope, one peptide (positions F(100) to Y(108)) that facilitated the detection of infected animals independent of their vaccination status (DIVA function) was identified. The approach described overcomes the problems currently limiting the use of bacterial live vaccines and holds considerable potential for future developments in the field.
dc.language.isoenen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subject.meshAnimalsen
dc.subject.meshGenetic Markersen
dc.subject.meshHumansen
dc.subject.meshImmunizationen
dc.subject.meshMiceen
dc.subject.meshMice, Inbred BALB Cen
dc.subject.meshMolecular Sequence Dataen
dc.subject.meshMutationen
dc.subject.meshPorinsen
dc.subject.meshSalmonella Infectionsen
dc.subject.meshSalmonella Infections, Animalen
dc.subject.meshSalmonella Vaccinesen
dc.subject.meshSalmonella typhimuriumen
dc.subject.meshSwineen
dc.subject.meshSwine Diseasesen
dc.subject.meshVaccines, Attenuateden
dc.subject.meshVaccines, DNAen
dc.subject.meshVirulenceen
dc.subject.meshZoonosesen
dc.titleImmunization of pigs to prevent disease in humans: construction and protective efficacy of a Salmonella enterica serovar Typhimurium live negative-marker vaccine.en
dc.typeArticleen
dc.contributor.departmentnstitute for Microbiology, Department of Infectious Diseases, University of Veterinary Medicine Hannover, Hannover, Germany.en
dc.identifier.journalInfection and immunityen
refterms.dateFOA2018-06-13T05:29:43Z
html.description.abstractZoonotic infections caused by Salmonella enterica serovar Typhimurium pose a constant threat to consumer health, with the pig being a particularly major source of multidrug-resistant isolates. Vaccination, as a promising approach to reduce colonization and shedding, has been scarcely used, as it interferes with current control programs relying on serology as a means of herd classification. In order to overcome this problem, we set out to develop a negative-marker vaccine allowing the differentiation of infected from vaccinated animals (DIVA). Applying an immunoproteomic approach with two-dimensional gel electrophoresis, Western blot, and quadrupole time-of-flight tandem mass spectrometry, we identified the OmpD protein as a suitable negative marker. Using allelic exchange, we generated an isogenic mutant of the licensed live vaccine strain Salmoporc and showed that virulence of Salmoporc and that of the mutant strain, SalmoporcDeltaompD, were indistinguishable in BALB/c mice. In a pig infection experiment including two oral immunizations with SalmoporcDeltaompD and challenge with a multiresistant S. enterica serovar Typhimurium DT104 clinical isolate, we confirmed the protective efficacy of SalmoporcDeltaompD in pigs, showing a significant reduction of both clinical symptoms and colonization of lymph nodes and intestinal tract. OmpD immunogenic epitopes were determined by peptide spot array analyses. Upon testing of several 9-mer peptides, each including an immunogenic epitope, one peptide (positions F(100) to Y(108)) that facilitated the detection of infected animals independent of their vaccination status (DIVA function) was identified. The approach described overcomes the problems currently limiting the use of bacterial live vaccines and holds considerable potential for future developments in the field.


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