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To overcome the limitations of current vaccine design, structurally defined trisaccharides derived from\n                    <jats:italic>Salmonella<\/jats:italic>\n                    O\u2010polysaccharide backbones composed of D\u2010mannose\u2010\u03b1(1\u21924)\u2010L\u2010rhamnose\u2010\u03b1(1\u21923)\u2010D\u2010galactose\u2010\u03b1(1\u21922) sequence and differing only in\n                    <jats:italic>O<\/jats:italic>\n                    \u2010acetylation patterns on the rhamnose were synthesized and conjugated with mQ\u03b2 virus\u2010like particles. The resulting glycoconjugates elicited robust glycan\u2010specific antibody responses. Interestingly, while the vaccine based on the non\u2010acetylated antigen was not protective against typhoidal strains of\n                    <jats:italic>Salmonella<\/jats:italic>\n                    , rabbit antisera induced by the diacetylated rhamnose containing trisaccharide conjugate provided effective protection to mice against lethal challenges by four major pathogenic\n                    <jats:italic>Salmonella<\/jats:italic>\n                    serovars including both typhoidal and non\u2010typhoidal serovars. Mechanistic studies revealed that antigen di\u2010\n                    <jats:italic>O<\/jats:italic>\n                    \u2010acetylation significantly enhanced complement deposition and opsonophagocytosis of bacteria by the antibodies produced. This is the first time that a vaccine based on a single antigen protected against all four major pathogenic serovars to humans, opening new ground for broad spectrum anti\u2010\n                    <jats:italic>Salmonella<\/jats:italic>\n                    vaccine design. In addition, this suggests introduction of defined acetylation to synthetic\n                    <jats:italic>O<\/jats:italic>\n                    \u2010antigen can be a promising strategy for vaccine development as many bacterial O\u2010polysaccharides are modified by acetates in nature.\n                  <\/jats:p>","DOI":"10.1002\/advs.77776","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T05:31:08Z","timestamp":1789623068000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Critical Roles of\n                    <i>O<\/i>\n                    \u2010Acetylation Revealed by Synthetic Trisaccharide Antigens for a Broad\u2010Spectrum Anti\u2010\n                    <i>Salmonella<\/i>\n                    Vaccine"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4510-1051","authenticated-orcid":false,"given":"Xingling","family":"Pan","sequence":"first","affiliation":[{"name":"Department of Chemistry Michigan State University  East Lansing Michigan USA"},{"name":"Institute For Quantitative Health Science &amp; Engineering Michigan State University  East Lansing Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soham","family":"Maity","sequence":"additional","affiliation":[{"name":"Iaso Therapeutics Inc.  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