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dc.contributor.authorNasrin, Shamima
dc.contributor.authorFuche, Fabien J
dc.contributor.authorSears, Khandra T
dc.contributor.authorJones, Jennifer A
dc.contributor.authorLevine, Myron M
dc.contributor.authorSimon, Raphael
dc.contributor.authorTennant, Sharon M
dc.date.accessioned2021-02-05T20:19:42Z
dc.date.available2021-02-05T20:19:42Z
dc.date.issued2021-01-16
dc.identifier.urihttp://hdl.handle.net/10713/14490
dc.description.abstractNon-typhoidal Salmonella (NTS) is a major cause of gastroenteritis and is responsible for approximately 93 million cases annually. In healthy individuals, gastroenteritis caused by NTS is usually self-limiting, however, NTS can cause severe invasive disease in immunocompromised patients. Very little research has been directed towards development of vaccines against Salmonella serogroups O:6,7 or O:8. We have constructed a live attenuated serogroup O:8 vaccine, CVD 1979, by deleting guaBA, htrA, and aroA from the genome of S. Newport. We have shown that the candidate vaccine is well tolerated in mice and elicits serum immunoglobulin G (IgG) antibodies against core O-polysaccharide (COPS) when administered orally. Immunized mice were challenged intraperitoneally with wild-type S. Newport and bacterial burden in the liver and spleen was found to be significantly reduced in the livers of immunized mice compared to control mice. We also observed moderate vaccine efficacy (45%) against lethal challenge with the serogroup O:8 serovar, S. Muenchen, but low vaccine efficacy (28%) following lethal challenge with a serogroup O:6,7 serovar, S. Virchow. In vitro, we have shown that antibodies generated by CVD 1979 only recognize lipopolysaccharide (LPS) from serogroup O:8 but not serogroup O:6,7 serovars, and that they mediate opsonophagocytic antibody (OPA) activity against serogroup O:8 but not serogroup O:6,7 serovars. We also showed that OPA activity can be blocked by pre-incubating the antisera with serogroup O:8 lipopolysaccharide. Taken together, our data demonstrate that we have constructed a well-tolerated, effective live attenuated S. Newport vaccine which elicits functional antibodies against serogroup O:8 but not O:6,7 serovars.en_US
dc.description.urihttps://doi.org/10.3390/vaccines9010057en_US
dc.language.isoenen_US
dc.publisherMDPI AGen_US
dc.relation.ispartofVaccinesen_US
dc.subjectMuenchenen_US
dc.subjectNewporten_US
dc.subjectSalmonellaen_US
dc.subjectattenuateden_US
dc.subjectliveen_US
dc.subjectvaccineen_US
dc.titleRefinement of a Live Attenuated Salmonella enterica Serovar Newport Vaccine with Improved Safetyen_US
dc.typeArticleen_US
dc.identifier.doi10.3390/vaccines9010057
dc.identifier.pmid33467190
dc.source.volume9
dc.source.issue1
dc.source.countryUnited States
dc.source.countrySwitzerland


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