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dc.contributor.authorMicoli, Francescaen
dc.contributor.authorRondini, Simonaen
dc.contributor.authorAlfini, Renzoen
dc.contributor.authorLanzilao, Luisaen
dc.contributor.authorNecchi, Francescaen
dc.contributor.authorNegrea, Aurelen
dc.contributor.authorRossi, Omaren
dc.contributor.authorBrandt, Corneliaen
dc.contributor.authorClare, Simonen
dc.contributor.authorMastroeni, Pietroen
dc.contributor.authorRappuoli, Rinoen
dc.contributor.authorSaul, Allanen
dc.contributor.authorMacLennan, Calman Aen
dc.date.accessioned2018-11-22T00:33:25Z
dc.date.available2018-11-22T00:33:25Z
dc.date.issued2018-10en
dc.identifier.issn0027-8424
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/285699
dc.description.abstractNontyphoidal Salmonellae cause a devastating burden of invasive disease in sub-Saharan Africa with high levels of antimicrobial resistance. Vaccination has potential for a major global health impact, but no licensed vaccine is available. The lack of commercial incentive makes simple, affordable technologies the preferred route for vaccine development. Here we compare equivalent Generalized Modules for Membrane Antigens (GMMA) outer membrane vesicles and O-antigen-CRM197 glycoconjugates to deliver lipopolysaccharide O-antigen in bivalent Salmonella Typhimurium and Enteritidis vaccines. Salmonella strains were chosen and tolR deleted to induce GMMA production. O-antigens were extracted from wild-type bacteria and conjugated to CRM197 Purified GMMA and glycoconjugates were characterized and tested in mice for immunogenicity and ability to reduce Salmonella infection. GMMA and glycoconjugate O-antigen had similar structural characteristics, O-acetylation, and glucosylation levels. Immunization with GMMA induced higher anti-O-antigen IgG than glycoconjugate administered without Alhydrogel adjuvant. With Alhydrogel, antibody levels were similar. GMMA induced a diverse antibody isotype profile with greater serum bactericidal activity than glycoconjugate, which induced almost exclusively IgG1. Immunization reduced bacterial colonization of mice subsequently infected with SalmonellaS Typhimurium numbers were lower in tissues of mice vaccinated with GMMA compared with glycoconjugate. S. Enteritidis burden in the tissues was similar in mice immunized with either vaccine. With favorable immunogenicity, low cost, and ability to induce functional antibodies and reduce bacterial burden, GMMA offer a promising strategy for the development of a nontyphoidal Salmonella vaccine compared with established glycoconjugates. GMMA technology is potentially attractive for development of vaccines against other bacteria of global health significance.
dc.format.mediumPrint-Electronicen
dc.languageengen
dc.publisherNational Academy of Sciences
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectAnimalsen
dc.subjectMiceen
dc.subjectSalmonella enteritidisen
dc.subjectSalmonella typhimuriumen
dc.subjectSalmonella Infectionsen
dc.subjectGlycoconjugatesen
dc.subjectO Antigensen
dc.subjectSalmonella Vaccinesen
dc.subjectAntibodies, Bacterialen
dc.subjectVaccinationen
dc.titleComparative immunogenicity and efficacy of equivalent outer membrane vesicle and glycoconjugate vaccines against nontyphoidal Salmonella.en
dc.typeArticle
prism.endingPage10433
prism.issueIdentifier41en
prism.publicationDate2018en
prism.publicationNameProceedings of the National Academy of Sciences of the United States of Americaen
prism.startingPage10428
prism.volume115en
dc.identifier.doi10.17863/CAM.33049
dcterms.dateAccepted2018-08-17en
rioxxterms.versionofrecord10.1073/pnas.1807655115en
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2018-10en
dc.contributor.orcidMastroeni, Pietro [0000-0003-3838-4962]
dc.contributor.orcidRappuoli, Rino [0000-0002-8827-254X]
dc.identifier.eissn1091-6490
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idMedical Research Council (G1100102)
pubs.funder-project-idBiotechnology and Biological Sciences Research Council (BB/M000982/1)


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Attribution-NonCommercial-NoDerivatives 4.0 International
Except where otherwise noted, this item's licence is described as Attribution-NonCommercial-NoDerivatives 4.0 International