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However, data on the detailed phenotypic, functional and metabolic characteristics of antigen (Ag)-specific cells following the third dose of mRNA vaccine remain scarce. Here, using flow cytometry and 45-parameter mass cytometry, we broadly investigate the phenotype, function and the single-cell metabolic profile of SARS-CoV-2-specific T and B cells up to 8 months after the third dose of mRNA vaccine in a cohort of 94 patients with MS treated with different DMT, including cladribine, dimethyl fumarate, fingolimod, interferon, natalizumab, teriflunomide, rituximab or ocrelizumab. Almost all patients display functional immune response to SARS-CoV-2. Different metabolic profiles characterize antigen-specific-T and -B cell response in fingolimod- and natalizumab-treated patients, whose immune response differs from all the other MS treatments.<\/jats:p>","DOI":"10.1038\/s41467-024-47013-0","type":"journal-article","created":{"date-parts":[[2024,3,29]],"date-time":"2024-03-29T10:01:55Z","timestamp":1711706515000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Immunosenescence and vaccine efficacy revealed by immunometabolic analysis of SARS-CoV-2-specific cells in multiple sclerosis patients"],"prefix":"10.1038","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3217-9821","authenticated-orcid":false,"given":"Sara","family":"De Biasi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Domenico","family":"Lo Tartaro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita","family":"Neroni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-8040-4926","authenticated-orcid":false,"given":"Moritz","family":"Rau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6278-4144","authenticated-orcid":false,"given":"Nikolaos","family":"Paschalidis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Borella","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Santacroce","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annamaria","family":"Paolini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4268-6552","authenticated-orcid":false,"given":"Lara","family":"Gibellini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-0906-9459","authenticated-orcid":false,"given":"Alin Liviu","family":"Ciobanu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michela","family":"Cuccorese","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tommaso","family":"Trenti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0251-7711","authenticated-orcid":false,"given":"Ignacio","family":"Rubio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Vitetta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-2242-0652","authenticated-orcid":false,"given":"Martina","family":"Cardi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9785-3883","authenticated-orcid":false,"given":"Rafael Jos\u00e9","family":"Arg\u00fcello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Ferraro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5381-1558","authenticated-orcid":false,"given":"Andrea","family":"Cossarizza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,3,29]]},"reference":[{"key":"47013_CR1","doi-asserted-by":"publisher","first-page":"828616","DOI":"10.3389\/fneur.2022.828616","volume":"13","author":"C Tornatore","year":"2022","unstructured":"Tornatore, C. et al. Vaccine response in patients with multiple sclerosis receiving teriflunomide. Front. Neurol. 13, 828616 (2022).","journal-title":"Front. Neurol."},{"key":"47013_CR2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-17292-4","volume":"11","author":"S De Biasi","year":"2020","unstructured":"De Biasi, S. et al. Marked T cell activation, senescence, exhaustion and skewing towards TH17 in patients with COVID-19 pneumonia. Nat. Commun. 11, 3434 (2020).","journal-title":"Nat. Commun."},{"key":"47013_CR3","doi-asserted-by":"publisher","first-page":"668","DOI":"10.1002\/cyto.a.24009","volume":"97","author":"A Cossarizza","year":"2020","unstructured":"Cossarizza, A. et al. Handling and processing of blood specimens from patients with COVID-19 for safe studies on cell phenotype and cytokine storm. Cytom. A 97, 668\u2013673 (2020).","journal-title":"Cytom. 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