{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:17:15Z","timestamp":1787026635724,"version":"build-2736575974"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,6,7]],"date-time":"2024-06-07T00:00:00Z","timestamp":1717718400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"\n Introduction<\/jats:title>\n \n Non-typhoidal\n Salmonella<\/jats:italic>\n (NTS) generally causes self-limiting gastroenteritis. However, older adults (\u226565 years) can experience more severe outcomes from NTS infection. We have previously shown that a live attenuated\n S<\/jats:italic>\n . Typhimurium vaccine, CVD 1926 (I77 \u0394\n guaBA<\/jats:italic>\n \u0394\n clpP<\/jats:italic>\n \u0394\n pipA<\/jats:italic>\n \u0394\n htrA<\/jats:italic>\n ), was immunogenic in adult but not aged mice. Here we describe modification of CVD 1926 through deletion of\n steD<\/jats:italic>\n , a\n Salmonella<\/jats:italic>\n effector responsible for host immune escape, which we hypothesized would increase immunogenicity in aged mice.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Mel Juso and\/or mutuDC cells were infected with\n S<\/jats:italic>\n . Typhimurium I77, CVD 1926, and their respective\n steD<\/jats:italic>\n mutants, and the MHC-II levels were evaluated. Aged (18-month-old) C57BL\/6 mice received two doses of PBS, CVD 1926, or CVD 1926 \u0394\n steD<\/jats:italic>\n perorally (10\n 9<\/jats:sup>\n CFU) and the number of FliC-specific CD4\n +<\/jats:sup>\n T cells were determined. Lastly, aged C57BL\/6 mice received three doses of PBS, CVD 1926, or CVD 1926 \u0394\n steD<\/jats:italic>\n perorally (10\n 9<\/jats:sup>\n CFU) and then were challenged perorally with wild-type\n S<\/jats:italic>\n . Typhimurium SL1344 (10\n 8<\/jats:sup>\n CFU). These animals were also evaluated for antibody responses.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n MHC-II induction was higher in cells treated with\n steD<\/jats:italic>\n mutants, compared to their respective parental strains. Compared to PBS-vaccinated mice, CVD 1926 \u0394\n steD<\/jats:italic>\n elicited significantly more FliC-specific CD4\n +<\/jats:sup>\n T cells in the Peyer\u2019s Patches. There were no significant differences in FliC-specific CD4\n +<\/jats:sup>\n T cells in the Peyer\u2019s patches or spleen of CVD 1926- versus PBS-immunized mice. CVD 1926 and CVD 1926 \u0394\n steD<\/jats:italic>\n induced similar serum and fecal anti-core and O polysaccharide antibody titers after three doses. After two immunizations, the proportion of seroconverters for CVD 1926 \u0394\n steD<\/jats:italic>\n was 83% (10\/12) compared to 42% (5\/12) for CVD 1926. Compared to PBS-immunized mice, mice immunized with CVD 1926 \u0394\n steD<\/jats:italic>\n had significantly lower\n S<\/jats:italic>\n . Typhimurium counts in the spleen, cecum, and small intestine upon challenge. In contrast, there were no differences in bacterial loads in the tissues of PBS-vaccinated and CVD 1926-immunized animals.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n These data suggest that the\n steD<\/jats:italic>\n deletion enhanced the immunogenicity of our live attenuated\n S<\/jats:italic>\n . Typhimurium vaccine. Deletion of immune evasion genes could be a potential strategy to improve the immunogenicity of live attenuated vaccines in older adults.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fimmu.2024.1376734","type":"journal-article","created":{"date-parts":[[2024,6,11]],"date-time":"2024-06-11T14:57:09Z","timestamp":1718117829000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Deletion of an immune evasion gene, steD, from a live Salmonella enterica serovar Typhimurium vaccine improves vaccine responses in aged mice"],"prefix":"10.3389","volume":"15","author":[{"given":"Jessica C.","family":"Allen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanaliz 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