{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T19:14:30Z","timestamp":1772565270204,"version":"3.50.1"},"reference-count":40,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T00:00:00Z","timestamp":1772496000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001826","name":"ZonMw","doi-asserted-by":"publisher","award":["10430072010002"],"award-info":[{"award-number":["10430072010002"]}],"id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Class switching toward spike (S)-binding IgG4 antibodies after mRNA-based COVID-19 vaccination has been observed, an antibody subclass with strong neutralizing but limited effector activity. While this has been reported in healthy individuals, subclass dynamics in immunocompromised kidney patients are unclear. We assessed IgG subclass patterns and S-specific B-cell phenotypes up to 6 months after a two-dose mRNA-1273 vaccination schedule in kidney transplant recipients (KTRs), dialysis patients, and patients with chronic kidney disease (CKD).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this exploratory study, KTRs (n\u2009=\u200911), dialysis patients (n\u2009=\u20095), CKD stage G4\u20135 patients (eGFR\u2009&lt;\u200930 ml\/min\/1.73m2, n\u2009=\u20095), and controls without known kidney disease (eGFR\u2009&gt;\u200945 ml\/min\/1.73m2, n\u2009=\u20098) received two mRNA-1273 doses 28 days apart. Blood was collected pre-vaccination (V1), and at 28 days (V3) and 6 months (V4) after the second dose. S1-specific IgG antibodies were measured by a validated fluorescent bead-based multiplex-immunoassay, and participants seronegative at V1 and seropositive at V3 were included. B cells were phenotyped by flow cytometry.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Five of 11 KTRs had no detectable S-binding B cells, whereas all other groups mounted responses. Across responders, the frequency of S-binding B cells increased from V1 (median 0.08%) to 0.49% at V3 and to 0.84% at V4 (both p\u2009&lt;\u20090.0001). S-binding B cells mainly comprised IgG\u207a plasmablasts. The IgG4:IgG1 log-ratio increased significantly from V3 to V4 (p\u2009&lt;\u20090.001), indicating a relative shift toward IgG4; absolute frequencies were comparable across the groups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Approximately half of KTRs lacked detectable S-binding B cells after two mRNA-1273 doses, despite antibody formation. Among responders, S-binding B cells persisted up to 6 months after vaccination with a relative shift toward IgG4, a pattern also observed in dialysis patients, CKD patients and controls. The clinical significance of this subclass skewing requires confirmation in larger cohorts with functional antibody readouts.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0336320","type":"journal-article","created":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T18:29:07Z","timestamp":1772562547000},"page":"e0336320","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Class switching toward IgG4 six months after primary mRNA-based COVID-19 vaccination in kidney patients"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5296-6104","authenticated-orcid":true,"given":"Sophie C.","family":"Fr\u00f6lke","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-9766-950X","authenticated-orcid":true,"given":"Kenney G.","family":"Amirkhan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nelly","family":"van der Bom-Baylon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marit","family":"van Gils","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mathieu","family":"Claireaux","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suzanne E.","family":"Geerlings","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rory D.","family":"de Vries","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan-Stephan F.","family":"Sanders","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4935-9765","authenticated-orcid":true,"given":"Luuk B.","family":"Hilbrands","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dimitri A.","family":"Diavatopoulos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2792-142X","authenticated-orcid":true,"given":"A. Lianne","family":"Messchendorp","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michiel C.","family":"van Aalderen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4694-6048","authenticated-orcid":true,"given":"Ester B. M.","family":"Remmerswaal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4454-6270","authenticated-orcid":true,"given":"Frederike J.","family":"Bemelman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2026,3,3]]},"reference":[{"key":"pone.0336320.ref001","doi-asserted-by":"crossref","first-page":"720402","DOI":"10.3389\/fmed.2021.720402","article-title":"End-Stage Renal Disease-Related Accelerated Immune Senescence: Is Rejuvenation of the Immune System a Therapeutic Goal?","volume":"8","author":"D Ducloux","year":"2021","journal-title":"Front Med (Lausanne)"},{"issue":"4","key":"pone.0336320.ref002","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1097\/TP.0000000000003983","article-title":"The RECOVAC Immune-response Study: The Immunogenicity, Tolerability, and Safety of COVID-19 Vaccination in 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