{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T17:41:31Z","timestamp":1777052491577,"version":"3.51.4"},"reference-count":28,"publisher":"BMJ","issue":"4","license":[{"start":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T00:00:00Z","timestamp":1776988800000},"content-version":"unspecified","delay-in-days":23,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["MRF2015313"],"award-info":[{"award-number":["MRF2015313"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2026,3,25]]},"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Immunosuppression is associated with an increased risk of delayed SARS-CoV-2 viral clearance, severe COVID-19 and related death. This heterogeneous group of affected patients includes but is not limited to those with a haematological malignancy, people on immunosuppressive therapy for the treatment of autoimmune\/inflammatory diseases and those following bone marrow transplantation (BMT). Immunosuppression is associated with decreased rates of anti-spike IgG seroconversion following COVID-19 vaccination. While clinical guidelines have been established to guide vaccination pre-splenectomy and post-BMT, there are limited data to guide timing of COVID-19 or other booster vaccines in adults commencing new or intensified moderate to severe immunosuppression. The comparison of immunity-boosting regimens for COVID-19 upon initiation of immunosuppressive therapy (CIRCUIT) study was designed to address this knowledge gap. CIRCUIT investigates whether administration of a third (or subsequent) COVID-19 booster vaccine \u22642 weeks prior to immunosuppression provides greater anti-spike IgG-mediated immunity than a booster given 24 weeks after new or intensified immunosuppression, that is, week 24 timepoint (Group 1; n=280). Additionally, the research will investigate whether giving a fourth post-BMT COVID-19 booster vaccine at 9\u2009months post-transplant provides greater anti-spike IgG-mediated immunity than a booster given 15 months post-transplant (Group 2; n=40).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>The CIRCUIT study is an open-label, multicentre randomised clinical trial. Participants will be randomised 1:1 to receive either an additional COVID-19 booster \u22642 weeks pre-immunosuppression and a diphtheria\/tetanus toxoids (DT) booster at 24 weeks following new or intensified immunosuppression (week 24 timepoint) or receive a DT booster \u22642 weeks pre-immunosuppression and an additional COVID-19 booster at week 24 (Group 1). Group 2 participants who underwent autologous or allogenic BMT in the last 9\u2009months will be randomised 1:1 to either receive a fourth post-BMT COVID-19 booster at 9 or 15\u2009months post-transplant. The primary outcome will be the integrated time-weighted area under the curve anti-SARS-CoV-2 neutralising antibody (NAb) response over 12 months from a SARS-CoV-2 booster as assessed by a high-throughput SARS-CoV-2 NAb platform assay. Key secondary outcomes of the CIRCUIT randomised control trial will include safety and generation of SARS-CoV-2 antigen specific T and B cell responses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>The research protocol was approved by the Western Sydney Local Health District Human Research Ethics Committee on 25 August 2022 (Ref no. 2022\/PID00782 \u2013 20022\/ETH0069). Study results will be published in peer-reviewed medical journals and presented at local and international conferences. All findings regardless of the outcome will be reported.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT05415267\">NCT05415267<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2025-115259","type":"journal-article","created":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T17:05:30Z","timestamp":1777050330000},"page":"e115259","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Comparison of immunity-boosting regimens for COVID-19 upon initiation of immunosuppressive therapy (CIRCUIT): study protocol for a randomised, controlled clinical trial"],"prefix":"10.1136","volume":"16","clinical-trial-number":[{"clinical-trial-number":"nct05415267","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0156-8143","authenticated-orcid":false,"given":"Dianne L","family":"Carey","sequence":"first","affiliation":[{"name":"The Kirby Institute, University of New South Wales, Sydney, New South Wales, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0026-1457","authenticated-orcid":false,"given":"Golo","family":"Ahlenstiel","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Blacktown and Mount Druitt Hospital, Sydney, New South Wales, Australia"},{"name":"Western Sydney University, Sydney, New South Wales, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabienne","family":"Brilot","sequence":"additional","affiliation":[{"name":"Kids Research, The Sydney Children\u2019s Hospitals Network, Sydney, New South Wales, Australia"},{"name":"The University of Sydney, Sydney, New South Wales, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David A","family":"Brown","sequence":"additional","affiliation":[{"name":"The University of Sydney, Sydney, New South Wales, Australia"},{"name":"New South Wales Health Pathology, ICPMR, Sydney, New South Wales, Australia"},{"name":"University of New South Wales, Sydney, New South Wales, Australia"},{"name":"Department of Clinical Immunology and Immunopathology, Westmead Hospital, Sydney, New South Wales, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rowena","family":"Bull","sequence":"additional","affiliation":[{"name":"The Kirby Institute, University of New South Wales, Sydney, New South Wales, Australia"},{"name":"School of Biomedical Sciences, University of New South Wales, Sydney, New South Wales, 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