{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T12:16:45Z","timestamp":1771417005003,"version":"3.50.1"},"reference-count":102,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T00:00:00Z","timestamp":1771372800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Live attenuated Salmonella enterica serovar Typhimurium has been investigated for decades as an orally delivered vaccine vector due to its ability to target the intestinal mucosa and engage both innate and adaptive immune responses. In humans, S. Typhimurium infection is largely restricted to the gastrointestinal tract, distinguishing it from Salmonella Typhi and providing a rationale for its use in mucosal vaccine strategies. In this review, we discuss the biological features of S. Typhimurium that support its use as a vaccine vector and summarize current understanding of the immune responses generated during wild-type infection, including innate activation and downstream T cell and B cell responses. We compare key biological differences between Salmonella Typhi and S. Typhimurium and outline emerging vector design strategies, including delayed attenuation and chromosomal integration of heterologous antigens. We then review applications of attenuated S. Typhimurium vectors targeting viral, bacterial, and parasitic pathogens, highlighting shared immunological outcomes and design principles across platforms. Finally, we discuss recent advances in vector engineering, including chromosomal integration of heterologous antigens, as well as remaining gaps in knowledge related to the durability of immune responses and translational considerations.<\/jats:p>","DOI":"10.3390\/microorganisms14020492","type":"journal-article","created":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T11:45:58Z","timestamp":1771415158000},"page":"492","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Current Applications and Immunological Considerations of Salmonella enterica Serovar Typhimurium as a Vaccine Vector"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4092-7172","authenticated-orcid":false,"given":"Adam S.","family":"Hassan","sequence":"first","affiliation":[{"name":"Faculty of Medicine and Health Sciences, McGill University, Montreal, QC H3G 2M1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaitlin","family":"Winter","sequence":"additional","affiliation":[{"name":"Vaccine Evaluation Center, BC Children\u2019s Hospital Research Institute, Vancouver, BC V5Z 4H4, Canada"},{"name":"Department of Pediatrics, University of British Columbia, Vancouver, BC V6H 3V4, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4832-3936","authenticated-orcid":false,"given":"Charles M.","family":"Dozois","sequence":"additional","affiliation":[{"name":"Centre Armand-Frappier Sant\u00e9 Biotechnologie, Institut National de Recherche Scientifique, Laval, QC H7V 1B7, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3251-958X","authenticated-orcid":false,"given":"Brian J.","family":"Ward","sequence":"additional","affiliation":[{"name":"Infectious Diseases and Immunity in Global Health Program, Research Institute of the McGill University Health Centre, Montreal, QC H4A 3J1, Canada"},{"name":"Department of Microbiology and Immunology, McGill University, Montreal, QC H3A 2B4, Canada"},{"name":"Division of Experimental Medicine, McGill University, Montreal, QC H4A 3J1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Momar","family":"Ndao","sequence":"additional","affiliation":[{"name":"Infectious Diseases and Immunity in Global Health Program, Research Institute of the McGill University Health Centre, Montreal, QC H4A 3J1, Canada"},{"name":"Department of Microbiology and Immunology, McGill University, Montreal, QC H3A 2B4, Canada"},{"name":"Division of Experimental Medicine, McGill University, Montreal, QC H4A 3J1, Canada"},{"name":"National Reference Centre for Parasitology, Research Institute of the McGill University Health Centre, Montreal, QC H4A 3J1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,18]]},"reference":[{"key":"ref_1","first-page":"73","article-title":"Advances in the development of new vaccines for bacterial and viral diseases","volume":"19","author":"Brentjens","year":"2003","journal-title":"Adv. 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