{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T22:40:41Z","timestamp":1791326441206,"version":"4.3.1"},"reference-count":81,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T00:00:00Z","timestamp":1761782400000},"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":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The COVID-19 pandemic highlighted challenges in managing patients with multiple sclerosis (PwMS), as disease-modifying therapies (DMTs) can interfere with immune responses to infections and vaccines.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study investigates the spike-specific T-cell response after the third dose of mRNA COVID-19 vaccines in PwMS undergoing DMTs, evaluating different cytokines, beyond IFN-\u03b3, and exploring their potential association with SARS-CoV-2 breakthrough infections (BI).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We prospectively enrolled 31 PwMS and 27 healthcare workers (HCWs). The spike-specific T-cell response was evaluated by measuring Th1 cytokines (IFN-\u03b3, IL-2, TNF-\u03b1) and IP-10 using an easy-to-use whole-blood assay.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Most PwMS mounted a Wuhan spike-specific T-cell response by releasing Th1 cytokines (IFN-\u03b3, IL-2, TNF-\u03b1) and IP-10, albeit with significantly reduced Th1 cytokine levels compared to HCWs. Fingolimod-treated patients showed the weakest response with significantly reduced IFN-\u03b3 and IL-2 levels compared to HCWs (both p&amp;lt;0.0001), as well as to ocrelizumab (p=0.0018 and p=0.0002, respectively) and cladribine\/IFN-\u03b2-treated patients (p=0.041 and p&amp;lt;0.0001, respectively). Moreover, a cell-mediated response was observed against the Delta spike variant, and all cytokines correlated with each other. BI occurred in 38.7% of PwMS, with predominantly mild COVID-19 cases. Male sex (IRR: 4.05, p=0.017) and primary progressive MS (IRR: 3.65, p=0.052) were associated with a higher BI incidence rate. Spike-specific T-cell response did not associate with a higher protection against BI.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study provides an in-depth immunological characterization of the spike-specific T-cell response in PwMS under DMTs, evaluating immunological biomarkers whose relevance may extend beyond COVID-19 for studying immune responses to other infections and vaccinations.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1682049","type":"journal-article","created":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T06:22:11Z","timestamp":1761805331000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Minimal association between Th1-specific responses to COVID-19 vaccines and SARS-CoV-2 breakthrough infections in multiple sclerosis patients receiving disease-modifying therapies"],"prefix":"10.3389","volume":"16","author":[{"given":"Alessandra","family":"Aiello","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Assunta","family":"Navarra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shalom","family":"Haggiag","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serena","family":"Ruggieri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilda","family":"Cuzzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Vanini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Salmi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"Notari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna 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