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dc.contributor.authorHegerle, N.
dc.contributor.authorChoi, M.
dc.contributor.authorSinclair, J.
dc.date.accessioned2019-06-21T18:46:25Z
dc.date.available2019-06-21T18:46:25Z
dc.date.issued2018
dc.identifier.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85053109880&doi=10.1371%2fjournal.pone.0203143&partnerID=40&md5=4d6a91e1ec300233e933ebe31fe62080
dc.identifier.urihttp://hdl.handle.net/10713/9683
dc.description.abstractKlebsiella pneumoniae (KP) and Pseudomonas aeruginosa (PA) are important human pathogens that are associated with a range of infection types, including wound and disseminated infections. Treatment has been complicated by rising rates of antimicrobial resistance. Immunoprophylactic strategies are not constrained by antimicrobial resistance mechanisms. Vaccines against these organisms would be important public health tools, yet they are not available. KP surface O polysaccharides (OPS) are protective antigens in animal models of infection. Similarly, PA flagellin (Fla), the major subunit of the flagellar filament, is required for virulence and is a target of protective antibodies in animal models. We report herein the development of a combined KP and PA glycoconjugate vaccine comprised of the four most common KP OPS types associated with human infections (O1, O2, O3, O5), chemically linked to the two Fla types of PA (FlaA, FlaB). Conjugation of KP OPS to PA Fla enhanced anti-polysaccharide immune responses and produced a formulation that generated antibody titers to the four KP OPS types and both PA Fla antigens in rabbits. Passive transfer of vaccine-induced rabbit antisera reduced the bacterial burden and protected mice against fatal intravenous KP infection. Mice passively transferred with conjugate-induced antisera were also protected against PA infection after thermal injury with a FlaB-expressing isolate, but not a FlaA isolate. Taken together, these promising preclinical results provide important proof-of-concept for a broad spectrum human vaccine to prevent KP and PA infections. Copyright 2018 Hegerle 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_US
dc.description.urihttps://dx.doi.org/10.1371/journal.pone.0203143en_US
dc.language.isoen-USen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.ispartofPLoS ONE
dc.subject.meshKlebsiella Infections--prevention & controlen_US
dc.subject.meshPseudomonas Infections--prevention & controlen_US
dc.subject.meshVaccinesen_US
dc.titleDevelopment of a broad spectrum glycoconjugate vaccine to prevent wound and disseminated infections with Klebsiella pneumoniae and Pseudomonas aeruginosaen_US
dc.typeArticleen_US
dc.identifier.doi10.1371/journal.pone.0203143
dc.identifier.pmid30188914


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