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Microbiol."],"abstract":"<jats:p>\n                    Non-typhoidal\n                    <jats:italic>Salmonella<\/jats:italic>\n                    (NTS) infections are a major cause of foodborne illness worldwide, and rising antimicrobial resistance underscores the need for effective vaccines. Live attenuated\n                    <jats:italic>Salmonella<\/jats:italic>\n                    strains have potential, but developing an effective vaccine remains a challenge. In this study, we built on the previously constructed attenuated\n                    <jats:italic>Salmonella<\/jats:italic>\n                    Typhimurium strain RAST002, which carries deletions of\n                    <jats:italic>manA<\/jats:italic>\n                    and\n                    <jats:italic>steD<\/jats:italic>\n                    , by introducing a\n                    <jats:italic>yejAE<\/jats:italic>\n                    operon deletion to generate RAST003, aiming to further enhance immune responses. Oral immunization with this single strain induced robust systemic IgG and mucosal sIgA responses, significantly increased CD4\n                    <jats:sup>+<\/jats:sup>\n                    and CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell frequencies, and markedly elevated IFN-\u03b3 production, indicating a dominant Th1-type cellular immune response, alongside increased IL-2 and TNF-\u03b1 levels supporting overall T cell activation. Immunized mice were fully protected against homologous\n                    <jats:italic>S<\/jats:italic>\n                    . Typhimurium challenge and exhibited significantly improved survival following heterologous\n                    <jats:italic>S<\/jats:italic>\n                    . Enteritidis exposure. These results demonstrate that combining LPS deficiency with targeted deletions of immune evasion genes generates a single, highly immunogenic\n                    <jats:italic>Salmonella<\/jats:italic>\n                    strain capable of inducing broad, protective immunity, providing a promising strategy for NTS vaccine development.\n                  <\/jats:p>","DOI":"10.3389\/fmicb.2026.1827967","type":"journal-article","created":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T05:57:37Z","timestamp":1781675857000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Deletion of steD gene and yejAE operons in LPS-deficient Salmonella elicits strong t cell immunity and complete protection against homologous serotypes"],"prefix":"10.3389","volume":"17","author":[{"given":"Guodong","family":"Zhou","sequence":"first","affiliation":[{"name":"College of Agriculture and Biology, Liaocheng University, Liaocheng","place":["Shandong, China"]},{"name":"Shandong Key Laboratory of Applied Technology for Protein and Peptide Drugs, Liaocheng University, Liaocheng","place":["Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Shandong Key Laboratory of Applied Technology for Protein and Peptide Drugs, Liaocheng University, Liaocheng","place":["Shandong, China"]},{"name":"College of Pharmaceutical Sciences and Food Engineering, Liaocheng University, Liaocheng","place":["Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingyu","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Agriculture and Biology, Liaocheng University, Liaocheng","place":["Shandong, China"]},{"name":"Shandong Key Laboratory of Applied Technology for Protein and Peptide Drugs, Liaocheng University, Liaocheng","place":["Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhili","family":"Luo","sequence":"additional","affiliation":[{"name":"College of Agriculture and Biology, Liaocheng University, Liaocheng","place":["Shandong, China"]},{"name":"Shandong Key Laboratory of Applied Technology for Protein and Peptide Drugs, Liaocheng University, Liaocheng","place":["Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengliang","family":"Cao","sequence":"additional","affiliation":[{"name":"College of Agriculture and Biology, Liaocheng University, Liaocheng","place":["Shandong, China"]},{"name":"Shandong Key Laboratory of Applied Technology for Protein and Peptide Drugs, Liaocheng University, Liaocheng","place":["Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yubao","family":"Li","sequence":"additional","affiliation":[{"name":"College of Agriculture and Biology, Liaocheng University, Liaocheng","place":["Shandong, China"]},{"name":"Shandong Key Laboratory of Applied Technology for Protein and Peptide Drugs, Liaocheng University, Liaocheng","place":["Shandong, China"]},{"name":"College of Pharmaceutical Sciences and Food Engineering, Liaocheng University, Liaocheng","place":["Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,17]]},"reference":[{"key":"B1","doi-asserted-by":"crossref","first-page":"435","DOI":"10.2307\/1591205","article-title":"Humoral responses and salmonellosis protection in chickens given a vitamin-dependent Salmonella typhimurium mutant.","volume":"35","author":"Alderton","year":"1991","journal-title":"Avian Dis."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1376734","DOI":"10.3389\/fimmu.2024.1376734","article-title":"Deletion of an immune evasion gene, steD, from a live Salmonella enterica serovar Typhimurium vaccine improves vaccine responses in aged mice.","volume":"15","author":"Allen","year":"2024","journal-title":"Front. 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