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Live attenuated vaccine strains offer advantages in terms of enhancing cell mediated immunity and allowing inoculation by the oral route. However, main failures of these vaccines are the limited cross-protection achieved against heterologous serovars and interference with serological monitoring for infection. We have recently shown that an attenuated <jats:italic>S.<\/jats:italic> Enteritidis strain (\u0394XIII) is protective against <jats:italic>S.<\/jats:italic> Typhimurium in a murine infection model. \u0394XIII strain harbours 13 chromosomal deletions that make it unable to produce the sigma factor RpoS and synthesize cyclic-di-GMP (c-di-GMP). In this study, our objectives were to test the protective effects of \u0394XIII strain in swine and to investigate if the use of \u0394XIII permits the discrimination of vaccinated from infected pigs. Results show that oral vaccination of pre-weaned piglets with \u0394XIII cross-protected against a challenge with <jats:italic>S.<\/jats:italic> Typhimurium by reducing faecal shedding and ileocaecal lymph nodes colonization, both at the time of weaning and slaughter. Vaccinated pigs showed neither faecal shedding nor tissue persistence of the vaccine strain at weaning, ensuring the absence of \u0394XIII strain by the time of slaughter. Moreover, lack of the SEN4316 protein in \u0394XIII strain allowed the development of a serological test that enabled the differentiation of infected from vaccinated animals (DIVA).<\/jats:p>","DOI":"10.1186\/s13567-019-0730-3","type":"journal-article","created":{"date-parts":[[2020,1,10]],"date-time":"2020-01-10T16:02:59Z","timestamp":1578672179000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["A DIVA vaccine strain lacking RpoS and the secondary messenger c-di-GMP for protection against salmonellosis in pigs"],"prefix":"10.1186","volume":"51","author":[{"given":"Carmen","family":"Gil","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina","family":"Latasa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Enrique","family":"Garc\u00eda-Ona","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isidro","family":"L\u00e1zaro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Javier","family":"Labairu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maite","family":"Echeverz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saioa","family":"Burgui","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bego\u00f1a","family":"Garc\u00eda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"I\u00f1igo","family":"Lasa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6207-1766","authenticated-orcid":false,"given":"Cristina","family":"Solano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,1,10]]},"reference":[{"key":"730_CR1","first-page":"5500","volume":"16","author":"EFSA Ecdc","year":"2018","unstructured":"Ecdc EFSA (2018) The European Union summary report on trends and sources of zoonoses, zoonotic agents and food-borne outbreaks in 2017. 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