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dc.contributor.authorGarcı´a, Patricia-
dc.contributor.authorMoscoso, Miriam-
dc.contributor.authorFuentes-Valverde, Vı´ctor-
dc.contributor.authorRodicio, M. Rosario-
dc.contributor.authorHerrera-Leo´n, Silvia-
dc.contributor.authorBou, Germa´n-
dc.date.accessioned2024-12-19T02:48:26Z-
dc.date.available2024-12-19T02:48:26Z-
dc.date.issued2023-04-
dc.identifier.citationOriginal Articleen_US
dc.identifier.urihttp://localhost:8080/xmlui/handle/123456789/9281-
dc.description.abstractAbstract Background: Salmonella enterica serovar Typhimurium (S. Typhimurium) has become an important intestinal pathogen worldwide and is responsible for lethal invasive infections in populations at risk. There is at present an unmet need for preventive vaccines. Methods: IRTA GN-3728 genome was sequenced by Illumina and D-glutamate and D-glutamate/ D-alanine knockout-auxotrophs were constructed. They were characterized using electron microscopy, growth/viability curves, reversion analysis, and motility/agglutination assays. Their potential as vaccine candidates were explored using two BALB/c mouse models for Salmonella infections: a systemic and an intestinal inflammation. Clinical signs/body weight and survival were monitored, mucosal lactoferrin and specific/cross-reactive IgA/IgG were quantified by enzyme-linked-immunosorbent assays and bacterial shedding/burden in fecal/tissues were evaluated. Results: The D-glutamate auxotroph, IRTA DmurI, is highly attenuated, immunogenic and fully protective against systemic infection. The IRTA DmurI Dalr DdadX double auxotroph, constructed to reinforce vaccine safety, showed a higher level of attenuation and was 100% effective against systemic disease. In the intestinal model, it proved to be safe, yielding a lowdegree of mucosal inflammation, short-term shedding and undetectable invasiveness in the long-term, while eliciting cross-reactive fecal IgA/serum IgG against clinically relevant multidrug-resistant (MDR) S. Typhimurium strains. It also conferred protection against homologous oral challenge, and protected mice from local and extra-intestinal dissemination caused by one MDR strain responsible for an international outbreak of highly severe human infections. Additionally, oral vaccination promoted extended survival after lethal heterologous infection. Conclusion: This study yielded a very safe S. Typhimurium vaccine candidate that could be further refined for mucosal application against disease in humans.en_US
dc.language.isoen_USen_US
dc.publisherElsevier Taiwan LLCen_US
dc.subjectD-glutamateen_US
dc.subjectD-alanineen_US
dc.subjectntestinal infection modelen_US
dc.subjectLive auxotrophic vaccinesen_US
dc.subjectMucosal vaccineen_US
dc.subjectNon-typhoidal Salmonella Typhimuriumen_US
dc.titleA highly-safe live auxotrophic vaccine protecting against disease caused by nontyphoidal Salmonella Typhimurium in miceen_US
dc.typeArticleen_US
Appears in Collections:VOL 56 NO 2 2023

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