Bendamustine impairs humoral but not cellular immunity to SARS-CoV-2 vaccination in rituximab-treated B-cell lymphoma–affected patients
BackgroundPatients with B-cell lymphoma are a fragile category of subjects, particularly exposed to infections and characterized by an impaired vaccination response due to the disease itself and, even more, to the chemotherapy regimen. For this reason, extensive knowledge of the immune response stat...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-12-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1322594/full |
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| author | Anna Vanni Lorenzo Salvati Alessio Mazzoni Alessio Mazzoni Giulia Lamacchia Manuela Capone Stefania Francalanci Seble Tekle Kiros Seble Tekle Kiros Lorenzo Cosmi Lorenzo Cosmi Benedetta Puccini Manuel Ciceri Benedetta Sordi Gian Maria Rossolini Gian Maria Rossolini Francesco Annunziato Francesco Annunziato Laura Maggi Francesco Liotta Francesco Liotta |
| author_facet | Anna Vanni Lorenzo Salvati Alessio Mazzoni Alessio Mazzoni Giulia Lamacchia Manuela Capone Stefania Francalanci Seble Tekle Kiros Seble Tekle Kiros Lorenzo Cosmi Lorenzo Cosmi Benedetta Puccini Manuel Ciceri Benedetta Sordi Gian Maria Rossolini Gian Maria Rossolini Francesco Annunziato Francesco Annunziato Laura Maggi Francesco Liotta Francesco Liotta |
| author_sort | Anna Vanni |
| collection | DOAJ |
| description | BackgroundPatients with B-cell lymphoma are a fragile category of subjects, particularly exposed to infections and characterized by an impaired vaccination response due to the disease itself and, even more, to the chemotherapy regimen. For this reason, extensive knowledge of the immune response status of these subjects is of fundamental importance to obtain possible indications for a tailored immunization strategy.MethodsWe enrolled two cohorts of patients with B-cell lymphoma under rituximab treatment or 3–24 months after treatment. In all patients, we evaluated both humoral and cellular immunological memory toward SARS-CoV-2, after standard vaccination and upon one booster dose.ResultsWe observed no Spike-specific IgG production in patients (n = 25) under anti-CD20 treatment, whereas patients (n = 16) vaccinated after the completion of chemotherapy showed a higher humoral response. Evaluating SARS-CoV-2–specific T-cell response, we found that patients in both cohorts had developed robust cellular immunity after vaccination. Of the 21 patients (51%) that experienced a breakthrough SARS-CoV-2 infection, only six patients developed severe disease. Interestingly, these six patients had all been treated with rituximab plus bendamustine. Notably, we observed that Spike-specific IgG levels in patients treated with rituximab plus bendamustine were absent or lower compared with those in patients treated with rituximab plus other chemotherapy, whereas Spike-specific T-cell response was not different based on chemotherapy regiment.DiscussionOur results show that, in patients with B-cell lymphoma under rituximab therapy, anti–SARS-CoV-2 mRNA vaccination induces a weak or absent humoral response but a consistent T-cell response. In addition, chemotherapy regimens with bendamustine further reduce patients’ ability to mount a Spike-specific humoral response even after a long time period from chemotherapy discontinuation. These results provide evidence that different chemotherapeutics display different immunosuppressive properties that could be taken in to account in the choice of the right drug regimen for the right patient. Moreover, they question whether immunocompromised patients, particularly those treated with bendamustine, need interventions to improve vaccine-induced immune response. |
| first_indexed | 2024-03-09T10:39:23Z |
| format | Article |
| id | doaj.art-2d129dd8ff754e8990e64224ad8fb630 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-09T10:39:23Z |
| publishDate | 2023-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-2d129dd8ff754e8990e64224ad8fb6302023-12-01T17:29:58ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-12-011410.3389/fimmu.2023.13225941322594Bendamustine impairs humoral but not cellular immunity to SARS-CoV-2 vaccination in rituximab-treated B-cell lymphoma–affected patientsAnna Vanni0Lorenzo Salvati1Alessio Mazzoni2Alessio Mazzoni3Giulia Lamacchia4Manuela Capone5Stefania Francalanci6Seble Tekle Kiros7Seble Tekle Kiros8Lorenzo Cosmi9Lorenzo Cosmi10Benedetta Puccini11Manuel Ciceri12Benedetta Sordi13Gian Maria Rossolini14Gian Maria Rossolini15Francesco Annunziato16Francesco Annunziato17Laura Maggi18Francesco Liotta19Francesco Liotta20Department of Experimental and Clinical Medicine, University of Florence, Florence, ItalyDepartment of Experimental and Clinical Medicine, University of Florence, Florence, ItalyDepartment of Experimental and Clinical Medicine, University of Florence, Florence, ItalyFlow Cytometry Diagnostic Center and Immunotherapy, Careggi University Hospital, Florence, ItalyDepartment of Experimental and Clinical Medicine, University of Florence, Florence, ItalyDepartment of Experimental and Clinical Medicine, University of Florence, Florence, ItalyFlow Cytometry Diagnostic Center and Immunotherapy, Careggi University Hospital, Florence, ItalyDepartment of Experimental and Clinical Medicine, University of Florence, Florence, ItalyInfectious and Tropical Diseases Unit, Careggi University Hospital, Florence, ItalyDepartment of Experimental and Clinical Medicine, University of Florence, Florence, ItalyImmunoallergology Unit, Careggi University Hospital, Florence, ItalyHematology Unit, Careggi University Hospital, Florence, ItalyHematology Unit, Careggi University Hospital, Florence, ItalyHematology Unit, Careggi University Hospital, Florence, ItalyDepartment of Experimental and Clinical Medicine, University of Florence, Florence, ItalyMicrobiology and Virology Unit, Careggi University Hospital, Florence, ItalyDepartment of Experimental and Clinical Medicine, University of Florence, Florence, ItalyFlow Cytometry Diagnostic Center and Immunotherapy, Careggi University Hospital, Florence, ItalyDepartment of Experimental and Clinical Medicine, University of Florence, Florence, ItalyDepartment of Experimental and Clinical Medicine, University of Florence, Florence, ItalyImmunology and Cell Therapy Unit, Careggi University Hospital, Florence, ItalyBackgroundPatients with B-cell lymphoma are a fragile category of subjects, particularly exposed to infections and characterized by an impaired vaccination response due to the disease itself and, even more, to the chemotherapy regimen. For this reason, extensive knowledge of the immune response status of these subjects is of fundamental importance to obtain possible indications for a tailored immunization strategy.MethodsWe enrolled two cohorts of patients with B-cell lymphoma under rituximab treatment or 3–24 months after treatment. In all patients, we evaluated both humoral and cellular immunological memory toward SARS-CoV-2, after standard vaccination and upon one booster dose.ResultsWe observed no Spike-specific IgG production in patients (n = 25) under anti-CD20 treatment, whereas patients (n = 16) vaccinated after the completion of chemotherapy showed a higher humoral response. Evaluating SARS-CoV-2–specific T-cell response, we found that patients in both cohorts had developed robust cellular immunity after vaccination. Of the 21 patients (51%) that experienced a breakthrough SARS-CoV-2 infection, only six patients developed severe disease. Interestingly, these six patients had all been treated with rituximab plus bendamustine. Notably, we observed that Spike-specific IgG levels in patients treated with rituximab plus bendamustine were absent or lower compared with those in patients treated with rituximab plus other chemotherapy, whereas Spike-specific T-cell response was not different based on chemotherapy regiment.DiscussionOur results show that, in patients with B-cell lymphoma under rituximab therapy, anti–SARS-CoV-2 mRNA vaccination induces a weak or absent humoral response but a consistent T-cell response. In addition, chemotherapy regimens with bendamustine further reduce patients’ ability to mount a Spike-specific humoral response even after a long time period from chemotherapy discontinuation. These results provide evidence that different chemotherapeutics display different immunosuppressive properties that could be taken in to account in the choice of the right drug regimen for the right patient. Moreover, they question whether immunocompromised patients, particularly those treated with bendamustine, need interventions to improve vaccine-induced immune response.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1322594/fullSARS-CoV-2mRNA vaccineB cell lymphomaanti-CD20mAbrituximabbendamustine |
| spellingShingle | Anna Vanni Lorenzo Salvati Alessio Mazzoni Alessio Mazzoni Giulia Lamacchia Manuela Capone Stefania Francalanci Seble Tekle Kiros Seble Tekle Kiros Lorenzo Cosmi Lorenzo Cosmi Benedetta Puccini Manuel Ciceri Benedetta Sordi Gian Maria Rossolini Gian Maria Rossolini Francesco Annunziato Francesco Annunziato Laura Maggi Francesco Liotta Francesco Liotta Bendamustine impairs humoral but not cellular immunity to SARS-CoV-2 vaccination in rituximab-treated B-cell lymphoma–affected patients Frontiers in Immunology SARS-CoV-2 mRNA vaccine B cell lymphoma anti-CD20mAb rituximab bendamustine |
| title | Bendamustine impairs humoral but not cellular immunity to SARS-CoV-2 vaccination in rituximab-treated B-cell lymphoma–affected patients |
| title_full | Bendamustine impairs humoral but not cellular immunity to SARS-CoV-2 vaccination in rituximab-treated B-cell lymphoma–affected patients |
| title_fullStr | Bendamustine impairs humoral but not cellular immunity to SARS-CoV-2 vaccination in rituximab-treated B-cell lymphoma–affected patients |
| title_full_unstemmed | Bendamustine impairs humoral but not cellular immunity to SARS-CoV-2 vaccination in rituximab-treated B-cell lymphoma–affected patients |
| title_short | Bendamustine impairs humoral but not cellular immunity to SARS-CoV-2 vaccination in rituximab-treated B-cell lymphoma–affected patients |
| title_sort | bendamustine impairs humoral but not cellular immunity to sars cov 2 vaccination in rituximab treated b cell lymphoma affected patients |
| topic | SARS-CoV-2 mRNA vaccine B cell lymphoma anti-CD20mAb rituximab bendamustine |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1322594/full |
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