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Meanwhile, <jats:italic>Staphylococcus aureus<\/jats:italic> (SA) has resisted human vaccine development to date. Here we show that prior SA exposure induces non-protective CD4<jats:sup>+<\/jats:sup> T cell imprints, leading to the blunting of protective IsdB vaccine responses. Mechanistically, these SA-experienced CD4<jats:sup>+<\/jats:sup> T cells express IL-10, which is further amplified by vaccination and impedes vaccine protection by binding with IL-10R\u03b1 on CD4<jats:sup>+<\/jats:sup> T cell and inhibit IL-17A production. IL-10 also mediates cross-suppression of IsdB and sdrE multi-antigen vaccine. By contrast, the inefficiency of SA IsdB, IsdA and MntC vaccines can be overcome by co-treatment with adjuvants that promote IL-17A and IFN-\u03b3 responses. We thus propose that IL-10 secreting, SA-experienced CD4<jats:sup>+<\/jats:sup> T cell imprints represent a staphylococcal immune escaping mechanism that needs to be taken into consideration for future vaccine development.<\/jats:p>","DOI":"10.1038\/s41467-024-54644-w","type":"journal-article","created":{"date-parts":[[2024,12,16]],"date-time":"2024-12-16T10:05:27Z","timestamp":1734343527000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Pathobiont-induced suppressive immune imprints thwart T cell vaccine responses"],"prefix":"10.1038","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4010-1845","authenticated-orcid":false,"given":"Irshad Ahmed","family":"Hajam","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih-Ming","family":"Tsai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cesia","family":"Gonzalez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0563-8815","authenticated-orcid":false,"given":"Juan Raphael","family":"Caldera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6098-8052","authenticated-orcid":false,"given":"Mar\u00eda","family":"L\u00e1zaro D\u00edez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6907-3609","authenticated-orcid":false,"given":"Xin","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2944-3417","authenticated-orcid":false,"given":"April","family":"Aralar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-9482-416X","authenticated-orcid":false,"given":"Brian","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Duong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0759-0587","authenticated-orcid":false,"given":"George Y.","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,12,16]]},"reference":[{"key":"54644_CR1","doi-asserted-by":"publisher","first-page":"705","DOI":"10.1038\/s41586-018-0730-x","volume":"563","author":"D Gerlach","year":"2018","unstructured":"Gerlach, D. et al. 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