{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T10:47:22Z","timestamp":1791542842794,"version":"4.3.4"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T00:00:00Z","timestamp":1785369600000},"content-version":"vor","delay-in-days":29,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003579","name":"University of Toronto","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003579","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Canadian Institutes of Health Research (CIHR)\/COVID-Immunity Task Force","award":["GA2-177716"],"award-info":[{"award-number":["GA2-177716"]}]},{"name":"CIHR Canada Graduate Scholarships Doctoral","award":["FBD-187492"],"award-info":[{"award-number":["FBD-187492"]}]},{"name":"Canada Research Chair in Anti-viral Immunity, University of Toronto"},{"name":"Psoriatic Arthritis Research at UHN"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Anti-TNF and anti-IL-12\/IL-23 are commonly used therapies for immune-mediated inflammatory diseases (IMIDs), including inflammatory bowel disease (IBD). Although several studies have shown intact T cell responses following 2 to 3 doses of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in biologics treated IMID patients, our group previously reported increased waning of T cell responses at 3\u20134\u2009mos following the second vaccine dose in IMID patients compared to healthy controls, raising the possibility that a suboptimal initial T cell response could impact long term immunity. Here, to reduce patient heterogeneity, we focused only on IBD patients and further investigated T cell responses in vaccinated, untreated and biologics treated IBD patients compared to healthy controls. Following 1 vaccine dose, we observed a decreased frequency of Spike-reactive Th1 polarized cells and an increased frequency of Th2 cells in the IBD patients in general, relative to healthy controls. Additionally, IBD patients exhibited increased waning of Spike-specific cytokine T cell responses after 2 doses of vaccine. We also observed IBD-treatment specific effects. Spike-specific IL-2 secretion from anti-TNF or anti\u2013IL-12\/IL-23\u2013treated patients\u2019 T cells was lower than from untreated patients following 1 dose of vaccine. However, single-cell RNA-sequencing of Spike-responsive T cells from anti-TNF and anti\u2013IL-12\/IL-23 treated IBD patients and healthy controls 2\u20134\u2009wk after 2 or 3 vaccine doses revealed no major differences in T cell subsets, transcriptomes or TCR diversity. Thus, despite some evidence of impaired primary T cell responses, Spike-reactive T cells in patients treated with anti-TNF or anti\u2013IL-12\/IL-23 appear indistinguishable from healthy controls following a full vaccine course.<\/jats:p>","DOI":"10.1093\/jimmun\/vkag173","type":"journal-article","created":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:33:08Z","timestamp":1785421988000},"source":"Crossref","is-referenced-by-count":1,"title":["T cell immunity to SARS-CoV-2 vaccination in inflammatory bowel disease patients treated with anti-cytokine biologics"],"prefix":"10.1093","volume":"215","author":[{"given":"Michelle W","family":"Cheung","sequence":"first","affiliation":[{"name":"Department of Immunology, University of Toronto , Toronto, Ontario,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenny D","family":"Choi","sequence":"additional","affiliation":[{"name":"Lunenfeld-Tanenbaum Research Institute at Mount Sinai Hospital, Sinai Health System , Toronto, Ontario,","place":["Canada"]},{"name":"Zane Cohen Centre for Digestive Diseases, Division of Gastroenterology, Mount Sinai Hospital, Sinai Health System , Toronto, Ontario,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanne M","family":"Stempak","sequence":"additional","affiliation":[{"name":"Lunenfeld-Tanenbaum Research Institute at Mount Sinai Hospital, Sinai Health System , Toronto, Ontario,","place":["Canada"]},{"name":"Zane Cohen Centre for Digestive Diseases, Division of Gastroenterology, Mount Sinai Hospital, Sinai Health System , Toronto, Ontario,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8297-0275","authenticated-orcid":false,"given":"Vinod","family":"Chandran","sequence":"additional","affiliation":[{"name":"Gladman Krembil Psoriatic Arthritis Program, Schroeder Arthritis Institute, University Health Network , Toronto, Ontario,","place":["Canada"]},{"name":"Division of Rheumatology, Department of Medicine, University of Toronto , Toronto, Ontario,","place":["Canada"]},{"name":"Department of Laboratory Medicine and Pathobiology, University of Toronto , Toronto, Ontario,","place":["Canada"]},{"name":"Institute of Medical Science, University of Toronto , Toronto, Ontario,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark S","family":"Silverberg","sequence":"additional","affiliation":[{"name":"Lunenfeld-Tanenbaum Research Institute at Mount Sinai Hospital, Sinai Health System , Toronto, Ontario,","place":["Canada"]},{"name":"Zane Cohen Centre for Digestive Diseases, Division of Gastroenterology, Mount Sinai Hospital, Sinai Health System , Toronto, Ontario,","place":["Canada"]},{"name":"Division of Gastroenterology, Department of Medicine, University of Toronto , Toronto, Ontario,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7897-4890","authenticated-orcid":false,"given":"Tania H","family":"Watts","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Toronto , Toronto, Ontario,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,7,30]]},"reference":[{"key":"2026090710443587400_vkag173-B1","doi-asserted-by":"crossref","first-page":"ii3","DOI":"10.1093\/ecco-jcc\/jjae082","article-title":"Epidemiology of inflammatory bowel disease across the ages in the era of advanced therapies","volume":"18","author":"Caron","year":"2024","journal-title":"J Crohns Colitis."},{"key":"2026090710443587400_vkag173-B2","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1093\/ibd\/izy327","article-title":"A state-of-the-art review of new and emerging therapies for the treatment of IBD","volume":"25","author":"Chudy-Onwugaje","year":"2019","journal-title":"Inflamm Bowel Dis"},{"key":"2026090710443587400_vkag173-B3","doi-asserted-by":"publisher","DOI":"10.1172\/JCI192589","article-title":"Reduced vaccine-induced germinal center outputs in patients with inflammatory bowel disease treated with anti-TNF biologics","volume":"135","author":"Cheung","year":"2025","journal-title":"J Clin Invest"},{"key":"2026090710443587400_vkag173-B4","doi-asserted-by":"publisher","DOI":"10.1136\/rmdopen-2025-005724","article-title":"TNF inhibitors affect the induction and maintenance of spike-specific B-cell responses after mRNA vaccination","volume":"11","author":"Kummer","year":"2025","journal-title":"RMD Open"},{"key":"2026090710443587400_vkag173-B5","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.159721","article-title":"Accelerated waning of immunity to SARS-CoV-2 mRNA vaccines in patients with immune-mediated inflammatory diseases","volume":"7","author":"Dayam","year":"2022","journal-title":"JCI Insight"},{"key":"2026090710443587400_vkag173-B6","doi-asserted-by":"crossref","first-page":"351","DOI":"10.4049\/jimmunol.2300190","article-title":"Third and fourth vaccine doses broaden and prolong immunity to SARS-CoV-2 in adult patients with immune-mediated inflammatory diseases","volume":"211","author":"Cheung","year":"2023","journal-title":"J Immunol"},{"key":"2026090710443587400_vkag173-B7","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1016\/S2468-1253(22)00274-6","article-title":"COVID-19 vaccine-induced antibody and T-cell responses in immunosuppressed patients with inflammatory bowel disease after the third vaccine dose (VIP): a multicentre, prospective, case-control study","volume":"7","author":"Alexander","year":"2022","journal-title":"Lancet Gastroenterol Hepatol"},{"key":"2026090710443587400_vkag173-B8","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1053\/j.gastro.2021.10.029","article-title":"Lower serologic response to COVID-19 mRNA vaccine in patients with inflammatory bowel diseases treated with Anti-TNFalpha","volume":"162","author":"Edelman-Klapper","year":"2022","journal-title":"Gastroenterology"},{"key":"2026090710443587400_vkag173-B9","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1111\/apt.17661","article-title":"STAR SIGN study: evaluation of COVID-19 vaccine efficacy against the SARS-CoV-2 variants BQ.1.1 and XBB.1.5 in patients with inflammatory bowel disease","volume":"58","author":"Woelfel","year":"2023","journal-title":"Aliment Pharmacol Ther"},{"key":"2026090710443587400_vkag173-B10","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1136\/gutjnl-2021-324388","article-title":"Anti-SARS-CoV-2 antibody responses are attenuated in patients with IBD treated with infliximab","volume":"70","author":"Kennedy","year":"2021","journal-title":"Gut"},{"key":"2026090710443587400_vkag173-B11","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.1038\/s41467-022-28517-z","article-title":"Antibody decay, T cell immunity and breakthrough infections following two SARS-CoV-2 vaccine doses in inflammatory bowel disease patients treated with infliximab and vedolizumab","volume":"13","author":"Lin","year":"2022","journal-title":"Nat Commun"},{"key":"2026090710443587400_vkag173-B12","doi-asserted-by":"publisher","DOI":"10.1136\/rmdopen-2021-002008","article-title":"Humoral protection to SARS-CoV2 declines faster in patients on TNF alpha blocking therapies","volume":"7","author":"Geisen","year":"2021","journal-title":"RMD Open"},{"key":"2026090710443587400_vkag173-B13","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1038\/s41590-024-01787-z","article-title":"Antibody-independent protection against heterologous SARS-CoV-2 challenge conferred by 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