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dc.contributor.authorFuche, Fabien J.
dc.contributor.authorJones, Jennifer A.
dc.contributor.authorRamachandran, Girish
dc.contributor.authorHigginson, Ellen E.
dc.contributor.authorSimon, Raphael
dc.contributor.authorTennant, Sharon M.
dc.creatorFuche, F.
dc.date.accessioned2019-07-23T16:04:18Z
dc.date.available2019-07-23T16:04:18Z
dc.date.issued2019-07-12
dc.identifier.urihttps://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85049827898&origin=inward
dc.identifier.urihttp://hdl.handle.net/10713/10119
dc.description.abstractNon-typhoidal Salmonella (NTS) are a leading cause of foodborne infections worldwide, and serogroups B, C1, C2-C3 and D are the most common serogroups associated with human disease. While live vaccine candidates that protect against S. Typhimurium (serogroup B) and S. Enteritidis (serogroup D) have been described by us and others, far less effort has been directed towards vaccines that target either serogroup C1 or C2-C3 Salmonella. Here we describe a Salmonella Newport-based live-attenuated vaccine (serogroup C2-C3). Deletion of the genes clpX or rfaL, previously used in live vaccines to attenuate S. Typhimurium and/or S. Enteritidis, failed to attenuate S. Newport. However, we found that deletion of either guaBA or htrA raised the 50% lethal dose of S. Newport in an intraperitoneal infection model in BALB/c mice. Our live-attenuated vaccine candidate CVD 1966 (S. Newport ΔguaBA ΔhtrA) elicited strong antibody responses against COPS, flagellin and outer membrane proteins when administered intraperitoneally or orally. Following lethal challenge with the parental virulent strain of S. Newport, we observed vaccine efficacies of 53% for immunization via the intraperitoneal route and 47% for immunization via the oral route. Following intraperiteonal immunization, the vaccine also significantly reduced the bacterial burden of challenge organisms in the liver and spleen. Interestingly, reducing the LPS chain length by deleting rfaL did not induce a stronger immune response towards surface antigens, and failed to elicit any protection against lethal homologous challenge. In conclusion, we have developed a live-attenuated Salmonella serogroup C2-C3 vaccine that we are further evaluating. © 2018 The Author(s).en_US
dc.description.urihttps://doi.org/10.1080/21645515.2018.1491499en_US
dc.language.isoen_USen_US
dc.publisherTaylor and Francis Inc.en_US
dc.relation.ispartofHuman Vaccines and Immunotherapeuticsen_US
dc.subjectmouse modelen_US
dc.subjectNewporten_US
dc.subjectSalmonellaen_US
dc.subjectserogroup C2-C3en_US
dc.subjectvaccineen_US
dc.titleDeletions in guaBA and htrA but not clpX or rfaL constitute a live-attenuated vaccine strain of Salmonella Newport to protect against serogroup C2-C3 Salmonella in miceen_US
dc.typeArticleen_US
dc.identifier.doi10.1080/21645515.2018.1491499
dc.relation.volume15


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