{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T00:36:45Z","timestamp":1793147805059,"version":"4.5.0"},"reference-count":39,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T00:00:00Z","timestamp":1776816000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Hematology Unit of Brescia Civil Hospital","award":["123150"],"award-info":[{"award-number":["123150"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Background: Hematological patients have a high risk of developing severe COVID-19 (37%). Most mRNA vaccine trials in hematological patients showed a low immunogenicity after two doses, while long-term data are scarce. Methods: In this monocentric retrospective observational study, we evaluated humoral and T cell-mediated immune responses in 230 hematological patients after three doses of the Pfizer-BioNTech mRNA COVID-19 vaccine. Patients were stratified by age, disease type\/state, prior COVID-19 infection, and treatment status and regimens (anti-CD20 monoclonal antibodies, BTK and BCL-2 inhibitors, and treatment line). Antibody titer to SARS-CoV-2 was assessed by electrochemiluminescence immunoassay and T cell response by QuantiFERON interferon-\u03b3 release assay (IGRA). Data were analyzed using univariate (Fisher\u2019s exact test) and Firth\u2019s bias-reduced penalized-likelihood logistic regression. Results: A robust humoral response was observed with 91.55% of patients developing anti-spike antibodies (GMT 988.83 U\/mL). Anti-CD20-bendamustine treatment was associated with a significantly lower antibody positivity compared to untreated subjects. Prior COVID-19 infection significantly boosted both antibody positivity (95.9% vs. 85.2%) and GMT (847.02 U\/mL vs. 258.79 U\/mL). Conversely, T cell response was suboptimal (36.1% positive), particularly in anti-CD20-bendamustine-treated and multi-treated patients (27.1%), but highest in those treated with BTK inhibitors (50%). Multivariable logistic regression analysis linked multiple treatments to lower T cell response. Following vaccination, 29.1% of patients contracted SARS-CoV-2, but only 0.89% developed severe COVID-19. Conclusions: Three doses of mRNA vaccine elicit a strong humoral but a low T cell response, as detected by IGRA, in hematological patients. These findings underscore the importance of completing vaccination before initiating immunosuppressive therapies.<\/jats:p>","DOI":"10.3390\/vaccines14050369","type":"journal-article","created":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T12:54:08Z","timestamp":1776862448000},"page":"369","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Humoral and Cellular Immune Response in Patients with Hematological Disorders After Three Doses of mRNA COVID-19 Vaccine: A Single-Center Observational Study"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-4391-7673","authenticated-orcid":false,"given":"Rosa","family":"Daffini","sequence":"first","affiliation":[{"name":"Hematology Unit, ASST Spedali Civili of Brescia, 25123 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Zecchini","sequence":"additional","affiliation":[{"name":"Unit of Blood Diseases and Stem Cell Transplantation, ASST Spedali Civili of Brescia, Department of Clinical and Experimental Sciences, University of Brescia, 25123 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-7626-0997","authenticated-orcid":false,"given":"Giulia","family":"Venneri","sequence":"additional","affiliation":[{"name":"Section of Microbiology, ASST Spedali Civili of Brescia, Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0907-130X","authenticated-orcid":false,"given":"Michele","family":"Malagola","sequence":"additional","affiliation":[{"name":"Unit of Blood Diseases and Stem Cell Transplantation, ASST Spedali Civili of Brescia, Department of Clinical and Experimental Sciences, University of Brescia, 25123 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0031-3237","authenticated-orcid":false,"given":"Chiara","family":"Cattaneo","sequence":"additional","affiliation":[{"name":"Hematology Unit, ASST Spedali Civili of Brescia, 25123 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4996-7995","authenticated-orcid":false,"given":"Stefano","family":"Calza","sequence":"additional","affiliation":[{"name":"Unit of Biostatistics and Bioinformatics, Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnaldo","family":"Caruso","sequence":"additional","affiliation":[{"name":"Section of Microbiology, ASST Spedali Civili of Brescia, Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3052-7463","authenticated-orcid":false,"given":"Alessandra","family":"Tucci","sequence":"additional","affiliation":[{"name":"Hematology Unit, ASST Spedali Civili of Brescia, 25123 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4461-9353","authenticated-orcid":false,"given":"Cinzia","family":"Giagulli","sequence":"additional","affiliation":[{"name":"Section of Microbiology, ASST Spedali Civili of Brescia, Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e64","DOI":"10.1111\/bjh.16852","article-title":"Clinical outcome of coronavirus disease 2019 in haemato-oncology patients","volume":"190","author":"Aries","year":"2020","journal-title":"Br. J. Haematol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1111\/ejh.13519","article-title":"SARS-CoV-2 infection among patients with haematological disorders: Severity and one-month outcome in 66 Danish patients in a nationwide cohort study","volume":"106","author":"Jakobsen","year":"2021","journal-title":"Eur. J. Haematol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Casetti, I.C., Borsani, O., and Rumi, E. (2022). COVID-19 in Patients with Hematologic Diseases. Biomedicines, 10.","DOI":"10.3390\/biomedicines10123069"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1016\/j.clml.2023.04.002","article-title":"Clinical Outcomes in Patients With COVID-19 and Hematologic Disease","volume":"23","author":"Aleshina","year":"2023","journal-title":"Clin. Lymphoma Myeloma Leuk."},{"key":"ref_5","first-page":"127","article-title":"Clinical investigation of COVID-19 prevention and treatment","volume":"9","author":"Kulshrestha","year":"2024","journal-title":"Stem Cells"},{"key":"ref_6","first-page":"3","article-title":"Targets of SARS-CoV-2: Therapeutic implications for COVID-19","volume":"1","author":"Chadha","year":"2024","journal-title":"Stem Cells"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1412","DOI":"10.1056\/NEJMoa2101765","article-title":"BNT162b2 mRNA COVID-19 vaccine in a nationwide mass vaccination setting","volume":"384","author":"Dagan","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2603","DOI":"10.1056\/NEJMoa2034577","article-title":"Safety and efficacy of the BNT162b2 mRNA COVID-19 vaccine","volume":"383","author":"Polack","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1910","DOI":"10.1056\/NEJMoa2200674","article-title":"Safety and efficacy of a third dose of BNT162b2 COVID-19 vaccine","volume":"386","author":"Moreira","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1016\/j.medj.2022.04.013","article-title":"Safety and immunogenicity of the Pfizer\/BioNTech SARS-CoV-2 mRNA third booster vaccine dose against the BA.1 and BA.2 Omicron variants","volume":"3","author":"Seki","year":"2022","journal-title":"Med"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1016\/j.ijid.2021.11.009","article-title":"Real-world effectiveness of COVID-19 vaccines: A literature review and meta-analysis","volume":"114","author":"Zheng","year":"2022","journal-title":"Int. J. Infect. Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e583","DOI":"10.1016\/S2352-3026(21)00169-1","article-title":"Immunogenicity of the BNT162b2 COVID-19 mRNA vaccine and early clinical outcomes in patients with haematological malignancies in Lithuania: A national prospective cohort study","volume":"8","author":"Maneikis","year":"2021","journal-title":"Lancet Haematol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1038\/s41577-022-00716-1","article-title":"Disentangling the relative importance of T cell responses in COVID-19: Leading actors or supporting cast?","volume":"22","author":"Kent","year":"2022","journal-title":"Nat. Rev. Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1159\/000523753","article-title":"Vaccination for SARS-CoV-2 in hematological patients","volume":"145","author":"Riccardi","year":"2022","journal-title":"Acta Haematol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Post, N., Eddy, D., Huntley, C., van Schalkwyk, M.C.I., Shrotri, M., Leeman, D., Rigby, S., Williams, S.V., Bermingham, W.H., and Kellam, P. (2020). Antibody response to SARS-CoV2 infection in humans: A systematic review. PLoS ONE, 15.","DOI":"10.1101\/2020.08.25.20178806"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1007\/s00251-023-01294-9","article-title":"Role of T cells in severe COVID-19 disease, protection, and long term immunity","volume":"75","author":"Hermens","year":"2023","journal-title":"Immunogenetics"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"eabj1750","DOI":"10.1126\/sciimmunol.abj1750","article-title":"SARS-CoV-2 variants of concern partially escape humoral but not T-cell responses in COVID-19 convalescent donors and vaccines","volume":"6","author":"Geers","year":"2021","journal-title":"Sci. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1038\/s41392-021-00777-z","article-title":"SARS-CoV-2 immunity and functional recovery of COVID-19 patients 1-year after infection","volume":"6","author":"Zhan","year":"2021","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"5148","DOI":"10.1080\/21645515.2021.1991710","article-title":"Evaluation of the QuantiFERON SARS-CoV-2 assay to assess cellular immunogenicity of the BNT162b2 mRNA COVID-19 vaccine in individuals with low and high humoral response","volume":"17","author":"Tychala","year":"2021","journal-title":"Hum. Vaccin. Immunother."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Filippini, F., Giacomelli, M., Bazzani, C., Fredi, M., Semeraro, P., Tomasi, C., Franceschini, F., Caruso, A., Cavazzana, I., and Giagulli, C. (2023). Efficacy of COVID-19 mRNA vaccination in patients with autoimmune disorders: Humoral and cellular immune response. BMC Med., 21.","DOI":"10.1186\/s12916-023-02868-w"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Taffertshofer, K., Walter, M., Mackeben, P., Kraemer, J., Potapov, S., and Jochum, S. (2022). Design and performance characteristics of the Elecsys anti-SARS-CoV-2 S assay. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.1002576"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1038\/s41586-020-2598-9","article-title":"SARS-CoV2-reactive T cells in healthy donors and patients with COVID-19","volume":"587","author":"Braun","year":"2020","journal-title":"Nature"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3053","DOI":"10.1182\/bloodadvances.2021005094","article-title":"Efficacy of the BNT162b2 mRNA COVID-19 vaccine in patients with B-cell non-Hodgkin lymphoma","volume":"5","author":"Perry","year":"2021","journal-title":"Blood Adv."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1186\/s13045-021-01090-6","article-title":"Fifth-week immunogenicity and safety of anti-SARS-CoV-2 BNT162b2 vaccine in patients with multiple myeloma and myeloproliferative malignancies on active treatment: Preliminary data from a single institution","volume":"14","author":"Pimpinelli","year":"2021","journal-title":"J. Hematol. Oncol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e426","DOI":"10.1093\/cid\/ciac404","article-title":"Humoral and T-cell immune response after 3 doses of messenger RNA severe acute respiratory syndrome coronavirus 2 vaccines in fragile patients: The Italian VAX4FRAIL study","volume":"76","author":"Corradini","year":"2023","journal-title":"Clin. Infect. Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"101017","DOI":"10.1016\/j.xcrm.2023.101017","article-title":"Robust SARS-CoV-2 T cell responses with common TCRalphabeta motifs toward COVID-19 vaccines in patients with hematological malignancy impacting B cells","volume":"4","author":"Nguyen","year":"2023","journal-title":"Cell Rep. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1111\/bjh.17877","article-title":"T-cell immune response after mRNA SARS-CoV-2 vaccines is frequently detected also in the absence of seroconversion in patients with lymphoid malignancies","volume":"196","author":"Marasco","year":"2022","journal-title":"Br. J. Haematol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1182\/bloodadvances.2021006101","article-title":"Cellular and humoral immunogenicity of the mRNA-1273 SARS-CoV-2 vaccine in patients with hematologic malignancies","volume":"6","author":"Villacampa","year":"2022","journal-title":"Blood Adv."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e002036","DOI":"10.1136\/rmdopen-2021-002036","article-title":"Humoral and cellular immune responses on SARS-CoV-2 vaccines in patients with anti-CD20 therapies: A systematic review and meta-analysis of 1342 patients","volume":"8","author":"Schietzel","year":"2022","journal-title":"RMD Open"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"76","DOI":"10.2478\/raon-2026-0014","article-title":"Impaired booster-induced SARS-CoV-2 antibody responses in rituximab-treated B-cell lymphoma patients despite peripheral B-Cell Recovery","volume":"60","author":"Jurca","year":"2026","journal-title":"Radiol. Oncol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"128155","DOI":"10.1016\/j.vaccine.2025.128155","article-title":"Immunogenicity of SARS-CoV-2 primary vaccination and boosters in patients with immune-mediated inflammatory diseases: Impact of immunosuppressive therapy","volume":"73","author":"Larsen","year":"2026","journal-title":"Vaccine"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1038\/s41591-021-01377-8","article-title":"Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection","volume":"27","author":"Khoury","year":"2021","journal-title":"Nat. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"104820","DOI":"10.1016\/j.jcv.2021.104820","article-title":"Performance of the rapid high-throughput automated electrochemiluminescence immunoassay targeting total antibodies to the SARS-CoV-2 spike protein receptor binding domain in comparison to the neutralization assay","volume":"139","author":"Korva","year":"2021","journal-title":"J. Clin. Virol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"5069","DOI":"10.1002\/cncr.33160","article-title":"Clinical Characteristics and Risk Factors for Mortality in Hematologic Patients Affected By COVID-19","volume":"126","author":"Cattaneo","year":"2020","journal-title":"Cancer"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1280","DOI":"10.1038\/s41591-021-01386-7","article-title":"CD8+ T cells contribute to survival in patients with COVID-19 and hematologic cancer","volume":"27","author":"Bange","year":"2021","journal-title":"Nat. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2002","DOI":"10.1038\/s41591-021-01542-z","article-title":"Immune responses to two and three doses of the BNT162b2 mRNA vaccine in adults with solid tumors","volume":"27","author":"Shroff","year":"2021","journal-title":"Nat. Med."},{"key":"ref_37","first-page":"529","article-title":"Association between human leukocyte antigen alleles and COVID-19 severity: A systematic review and meta-analysis","volume":"20","year":"2022","journal-title":"J. Transl. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2351","DOI":"10.1038\/s41598-022-20773-9","article-title":"Experimental and clinical data analysis for identification of COVID-19 resistant ACE2 mutations","volume":"13","author":"Raghav","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1007\/s00726-021-02991-z","article-title":"Human cell receptors: Potential drug targets to combat COVID-19","volume":"53","author":"Raghav","year":"2021","journal-title":"Amino Acids"}],"container-title":["Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-393X\/14\/5\/369\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T13:00:00Z","timestamp":1776862800000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-393X\/14\/5\/369"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,22]]},"references-count":39,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["vaccines14050369"],"URL":"https:\/\/doi.org\/10.3390\/vaccines14050369","relation":{},"ISSN":["2076-393X"],"issn-type":[{"value":"2076-393X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,22]]}}}