Publication:
Brucellosis vaccines: assessment of brucella melitensis lipopolysaccharide rough mutants defective in core and O-polysaccharide synthesis and export

dc.contributor.authorGonzález, David
dc.contributor.authorGrilló Dolset, María Jesús
dc.contributor.authorMiguel, María Jesús de
dc.contributor.authorAli, Tara
dc.contributor.authorArce Gorvel, Vilma
dc.contributor.authorDelrue, Rose May
dc.contributor.authorConde Álvarez, Raquel
dc.contributor.authorMuñoz Álvaro, Pilar María
dc.contributor.authorLópez Goñi, Ignacio
dc.contributor.authorIriarte, Maite
dc.contributor.authorMarín, Clara M.
dc.contributor.authorWeintraub, Andrej
dc.contributor.authorWidmalm, Goeran
dc.contributor.authorZygmunt, Michel
dc.contributor.authorLetesson, Jean-Jacques
dc.contributor.authorGorvel, Jean-Pierre
dc.contributor.authorBlasco Canet, José María
dc.contributor.authorMoriyón Uría, Ignacio
dc.contributor.departmentIdAB. Instituto de Agrobiotecnología / Agrobioteknologiako Institutuaes_ES
dc.date.accessioned2014-06-11T09:18:09Z
dc.date.available2014-06-11T09:18:09Z
dc.date.issued2008
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.identifier.doi10.1371/journal.pone.0002760
dc.identifier.issn1932-6203
dc.identifier.other738
dc.identifier.urihttps://academica-e.unavarra.es/handle/2454/10815
dc.language.isoengen
dc.publisherPublic Library of Scienceen
dc.relation.ispartofPlos One, 2008, 3(7): e2760en
dc.relation.publisherversionhttps://dx.doi.org/10.1371/journal.pone.0002760
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.accessRightsinfo:eu-repo/semantics/openAccess
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.typeinfo:eu-repo/semantics/article
dc.type.versionVersión publicada / Argitaratu den bertsioaes
dc.type.versioninfo:eu-repo/semantics/publishedVersionen
dspace.entity.typePublication
relation.isAuthorOfPublication2eb9ac0b-533e-4c1d-ad93-f81b1fadee74
relation.isAuthorOfPublication.latestForDiscovery2eb9ac0b-533e-4c1d-ad93-f81b1fadee74

Files

Original bundle
Now showing 1 - 1 of 1
Loading...
Thumbnail Image
Name:
738.pdf
Size:
560.32 KB
Format:
Adobe Portable Document Format
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
1.71 KB
Format:
Item-specific license agreed to upon submission
Description: