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dc.creatorGonzález, Davides_ES
dc.creatorGrilló Dolset, María Jesúses_ES
dc.creatorMiguel, María Jesús dees_ES
dc.creatorAli, Taraes_ES
dc.creatorArce Gorvel, Vilmaes_ES
dc.creatorDelrue, Rose Mayes_ES
dc.creatorConde Álvarez, Raqueles_ES
dc.creatorMuñoz Álvaro, Pilar Maríaes_ES
dc.creatorLópez Goñi, Ignacioes_ES
dc.creatorIriarte, Maitees_ES
dc.creatorMarín, Clara M.es_ES
dc.creatorWeintraub, Andrejes_ES
dc.creatorWidmalm, Goeranes_ES
dc.creatorZygmunt, Micheles_ES
dc.creatorLetesson, Jean-Jacqueses_ES
dc.creatorGorvel, Jean-Pierrees_ES
dc.creatorBlasco, José Maríaes_ES
dc.creatorMoriyón Uría, Ignacioes_ES
dc.date.accessioned2014-06-11T09:18:09Z
dc.date.available2014-06-11T09:18:09Z
dc.date.issued2008
dc.identifier.issn1932-6203
dc.identifier.other738
dc.identifier.urihttps://hdl.handle.net/2454/10815
dc.description.abstractBackground: The brucellae are facultative intracellular bacteria that cause brucellosis, one of the major neglected zoonoses. In endemic areas, vaccination is the only effective way to control this disease. Brucella melitensis Rev 1 is a vaccine effective against the brucellosis of sheep and goat caused by B. melitensis, the commonest source of human infection. However, Rev 1 carries a smooth lipopolysaccharide with an O-polysaccharide that elicits antibodies interfering in serodiagnosis, a major problem in eradication campaigns. Because of this, rough Brucella mutants lacking the O-polysaccharide have been proposed as vaccines. Methodology/Principal Findings: To examine the possibilities of rough vaccines, we screened B. melitensis for lipopolysaccharide genes and obtained mutants representing all main rough phenotypes with regard to core oligosaccharide and O-polysaccharide synthesis and export. Using the mouse model, mutants were classified into four attenuation patterns according to their multiplication and persistence in spleens at different doses. In macrophages, mutants belonging to three of these attenuation patterns reached the Brucella characteristic intracellular niche and multiplied intracellularly, suggesting that they could be suitable vaccine candidates. Virulence patterns, intracellular behavior and lipopolysaccharide defects roughly correlated with the degree of protection afforded by the mutants upon intraperitoneal vaccination of mice. However, when vaccination was applied by the subcutaneous route, only two mutants matched the protection obtained with Rev 1 albeit at doses one thousand fold higher than this reference vaccine. These mutants, which were blocked in O-polysaccharide export and accumulated internal O-polysaccharides, stimulated weak anti-smooth lipopolysaccharide antibodies. Conclusions/Significance: The results demonstrate that no rough mutant is equal to Rev 1 in laboratory models and question the notion that rough vaccines are suitable for the control of brucellosis in endemic areas.en
dc.description.sponsorshipThis work was funded by the European Commission (Research Contract QLK2-CT-2002-00918) and the Ministerio de Ciencia y Tecnología of Spain (Proyecto AGL2004-01162/GAN).en
dc.format.mimetypeapplication/pdfen
dc.language.isoengen
dc.publisherPublic Library of Scienceen
dc.relation.ispartofPlos One, 2008, 3(7): e2760en
dc.rights© 2008 González et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/
dc.subjectBrucellosis vaccinesen
dc.subjectBrucella melitensisen
dc.subjectO-polysaccharideen
dc.subjectRough vaccinesen
dc.subjectMutantsen
dc.subjectRev 1en
dc.titleBrucellosis vaccines: assessment of brucella melitensis lipopolysaccharide rough mutants defective in core and O-polysaccharide synthesis and exporten
dc.typeArtículo / Artikuluaes
dc.typeinfo:eu-repo/semantics/articleen
dc.contributor.departmentIdAB - Instituto de Agrobiotecnología / Agrobioteknologiako Institutuaes
dc.rights.accessRightsAcceso abierto / Sarbide irekiaes
dc.rights.accessRightsinfo:eu-repo/semantics/openAccessen
dc.identifier.doi10.1371/journal.pone.0002760
dc.relation.publisherversionhttps://dx.doi.org/10.1371/journal.pone.0002760
dc.type.versionVersión publicada / Argitaratu den bertsioaes
dc.type.versioninfo:eu-repo/semantics/publishedVersionen


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© 2008 González et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Except where otherwise noted, this item's license is described as © 2008 González et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.