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dc.contributor.authorCoward, Chrisen
dc.contributor.authorRestif, Olivieren
dc.contributor.authorDybowski, Richarden
dc.contributor.authorGrant, Andrewen
dc.contributor.authorMaskell, Duncanen
dc.contributor.authorMastroeni, Pietroen
dc.date.accessioned2014-08-06T10:27:33Z
dc.date.available2014-08-06T10:27:33Z
dc.date.issued2014-09-18en
dc.identifier.citationPLOS ONE 10(9): e1004359en
dc.identifier.issn1553-7366
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/245624
dc.description.abstractSalmonella enterica infections are a significant global health issue and development of vaccines against these bacteria requires an improved understanding of how vaccination affects the growth and spread of the bacteria within the host. We have combined in vivo tracking of molecularly tagged bacterial subpopulations with mathematical modelling to gain a novel insight into how different classes of vaccines and branches of the immune response protect against secondary Salmonella enterica infections of the mouse. We have found that a live Salmonella vaccine significantly reduced bacteraemia during a secondary challenge and restrained inter-organ spread of the bacteria in the systemic organs. Further, fitting mechanistic models to the data indicated that live vaccine immunisation enhanced both the bacterial killing in the very early stages of the infection and bacteriostatic control over the first day post-challenge. T-cell immunity induced by this vaccine is not necessary for the enhanced bacteriostasis but is required for subsequent bactericidal clearance of Salmonella in the blood and tissues. Conversely, a non-living vaccine while able to enhance initial blood clearance and killing of virulent secondary challenge bacteria, was unable to alter the subsequent bacterial growth rate in the systemic organs, did not prevent the resurgence of extensive bacteraemia and failed to control the spread of the bacteria in the body.
dc.description.sponsorshipThis work was supported by the Biotechnology and Biological Sciences Research Council [grant number BB/I002189/1].
dc.languageEnglishen
dc.language.isoenen
dc.publisherPublic Library of Science
dc.rightsAttribution 2.0 UK: England & Wales*
dc.rights.urihttp://creativecommons.org/licenses/by/2.0/uk/*
dc.titleThe Effects of Vaccination and Immunity on Bacterial Infection Dynamics In Vivoen
dc.typeArticle
dc.description.versionThis is the published manuscript. It was originally published by PLOS One here: http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1004359.en
prism.publicationDate2014en
prism.publicationNamePLOS Oneen
prism.startingPagee1004359
prism.volume10en
dc.rioxxterms.funderBBSRC
dc.rioxxterms.projectidBB/I002189/1
dcterms.dateAccepted2014-07-25en
rioxxterms.versionofrecord10.1371/journal.ppat.1004359en
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2014-09-18en
dc.contributor.orcidRestif, Olivier [0000-0001-9158-853X]
dc.contributor.orcidGrant, Andrew [0000-0001-9746-2989]
dc.contributor.orcidMaskell, Duncan [0000-0002-5065-653X]
dc.contributor.orcidMastroeni, Pietro [0000-0003-3838-4962]
dc.identifier.eissn1553-7374
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idBBSRC (BB/I002189/1)
pubs.funder-project-idRoyal Society (uf120164)
pubs.funder-project-idMRC (G1100102)
pubs.funder-project-idBBSRC (BBS/B/02266)


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Attribution 2.0 UK: England & Wales
Except where otherwise noted, this item's licence is described as Attribution 2.0 UK: England & Wales