{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T16:58:17Z","timestamp":1778259497833,"version":"3.51.4"},"reference-count":33,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,7,22]],"date-time":"2025-07-22T00:00:00Z","timestamp":1753142400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Augustinus Fonden"},{"name":"Toyota Fonden"},{"name":"Grosserer L.F. Foghts Fond"},{"name":"KV Fonden"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Background: Kidney transplant recipients (KTRs) exhibit a significantly diminished immune response to Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) vaccines compared with the general population, primarily due to ongoing immunosuppressive therapy. This study evaluated the immunogenicity of a third SARS-CoV-2 mRNA vaccine dose in KTRs and assessed the association between antibody response and protection against SARS-CoV-2 breakthrough infection. Additionally, the clinical and immunological correlates of post-vaccination SARS-CoV-2 infection were examined. Methods: A prospective cohort of 135 KTRs received a third vaccine dose approximately six months following the second dose. Plasma samples were collected at baseline (pre-vaccination), six months after the second dose, and six weeks following the third dose. Humoral responses were assessed using SARS-CoV-2-specific Immunoglobulin G (IgG) titers and virus neutralization assays against wild-type (WT) and viral strains, including multiple Omicron sub-lineages. Results: After the third vaccine dose, 74% of the KTRs had detectable SARS-CoV-2-specific IgG antibodies, compared with 48% following the second dose. The mean IgG titers increased approximately ten-fold post-booster. Despite this increase, neutralizing activity against the Omicron variants remained significantly lower than that against the WT strain. KTRs who subsequently experienced a SARS-CoV-2 breakthrough infection demonstrated reduced neutralizing antibody activity across all variants tested. Additionally, individuals receiving triple immunosuppressive therapy had a significantly higher risk of SARS-CoV-2 breakthrough infection compared with those on dual or monotherapy. A multivariate machine learning analysis identified age and neutralizing activity against WT, Delta, and Omicron BA.2 as the most robust correlates of SARS-CoV-2 breakthrough infection. Conclusions: A third SARS-CoV-2 mRNA vaccine dose significantly improves SARS-CoV-2-specific IgG levels in KTRs; however, the neutralizing response against Omicron variants remains suboptimal. Diminished neutralizing capacity and intensified immunosuppression are key determinants of SARS-CoV-2 breakthrough infection in this immunocompromised population.<\/jats:p>","DOI":"10.3390\/vaccines13080777","type":"journal-article","created":{"date-parts":[[2025,7,22]],"date-time":"2025-07-22T15:00:42Z","timestamp":1753196442000},"page":"777","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Correlates of SARS-CoV-2 Breakthrough Infections in Kidney Transplant Recipients Following a Third SARS-CoV-2 mRNA Vaccine Dose"],"prefix":"10.3390","volume":"13","author":[{"given":"Miriam Viktov","family":"Thygesen","sequence":"first","affiliation":[{"name":"Department of Clinical Microbiology, Aarhus University Hospital, 8200 Aarhus, Denmark"},{"name":"Department of Medicine, G\u00f8dstrup Hospital, 7400 Herning, Denmark"},{"name":"Department of Renal Medicine, Aarhus University Hospital, 8200 Aarhus, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charlotte","family":"Strandhave","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Aalborg University Hospital, 9000 Aalborg, Denmark"},{"name":"Department of Clinical Medicine, Aalborg University, 9000 Aalborg, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeanette M\u00f8lgaard","family":"Kiib","sequence":"additional","affiliation":[{"name":"Department of Medicine, G\u00f8dstrup Hospital, 7400 Herning, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Randi","family":"Berg","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology, Aarhus University Hospital, 8200 Aarhus, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Malene S\u00f6th","family":"Andersen","sequence":"additional","affiliation":[{"name":"Department of Clinical Microbiology, Aarhus University Hospital, 8200 Aarhus, Denmark"},{"name":"Department of Clinical Medicine, Aarhus University, 8000 Aarhus, Denmark"},{"name":"Department of Clinical Epidemiology, Aarhus University, 8200 Aarhus, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emma Berggren","family":"Dall","sequence":"additional","affiliation":[{"name":"Department of Medicine, G\u00f8dstrup Hospital, 7400 Herning, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4042-5068","authenticated-orcid":false,"given":"Bodil Gade","family":"Hornstrup","sequence":"additional","affiliation":[{"name":"Department of Medicine, G\u00f8dstrup Hospital, 7400 Herning, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hans Christian","family":"\u00d8stergaard","sequence":"additional","affiliation":[{"name":"Department of Medicine, G\u00f8dstrup Hospital, 7400 Herning, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5830-5814","authenticated-orcid":false,"given":"Frank Holden","family":"Mose","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Aarhus University, 8000 Aarhus, Denmark"},{"name":"University Clinic in Nephrology and Hypertension, Department of Medicine, G\u00f8dstrup Hospital, 7400 Herning, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-3306-5165","authenticated-orcid":false,"given":"Jon Waarst","family":"Gregersen","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Aalborg University Hospital, 9000 Aalborg, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S\u00f8ren","family":"Jensen-Fangel","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Aarhus University Hospital, 8200 Aarhus, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0605-1277","authenticated-orcid":false,"given":"Jesper N\u00f8rgaard","family":"Bech","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Aarhus University, 8000 Aarhus, Denmark"},{"name":"University Clinic in Nephrology and Hypertension, Department of Medicine, G\u00f8dstrup Hospital, 7400 Herning, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henrik","family":"Birn","sequence":"additional","affiliation":[{"name":"Department of Renal Medicine, Aarhus University Hospital, 8200 Aarhus, Denmark"},{"name":"Department of Clinical Medicine, Aarhus University, 8000 Aarhus, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3645-6689","authenticated-orcid":false,"given":"Marianne Kragh","family":"Thomsen","sequence":"additional","affiliation":[{"name":"Department of Clinical Microbiology, Aarhus University Hospital, 8200 Aarhus, Denmark"},{"name":"Department of Clinical Medicine, Aarhus University, 8000 Aarhus, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rasmus","family":"Offersen","sequence":"additional","affiliation":[{"name":"Department of Medicine, G\u00f8dstrup Hospital, 7400 Herning, Denmark"},{"name":"Department of Infectious Diseases, Aarhus University Hospital, 8200 Aarhus, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2204","DOI":"10.1001\/jama.2021.7489","article-title":"Antibody Response to 2-Dose SARS-CoV-2 mRNA Vaccine Series in Solid Organ Transplant Recipients","volume":"325","author":"Boyarsky","year":"2021","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"547","DOI":"10.5578\/tt.20219612","article-title":"Immunogenicity of 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