Impaired SARS-CoV-2-Specific CD8+ T Cells After Infection or Vaccination but Robust Hybrid T Cell Immunity in Patients with Multiple Myeloma
Background: Multiple myeloma (MM) patients are at high risk of severe infections including COVID-19 due to an immune dysregulation affecting both innate and adaptive immune responses. However, our understanding of the immune responses to infection and vaccination in MM patients is limited. To gain m...
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2024-11-01
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| author | Khalid Shoumariyeh Benedikt Csernalabics Elahe Salimi Alizei Matthias Reinscheid Sebastian Giese Kevin Ciminski Georg Kochs Martin Schwemmle Julia Lang-Meli Michelle Maas Natascha Roehlen Vivien Karl Anne Graeser Oezlem Sogukpinar Ivana von Metzler Denise Grathwohl Leo Rasche Holger Hebart Miriam Kull Florian Emmerich Cornelius Florian Waller Justus Duyster Monika Engelhardt Tanja Nicole Hartmann Bertram Bengsch Tobias Boettler Christoph Neumann-Haefelin Maike Hofmann Robert Thimme Hendrik Luxenburger |
| author_facet | Khalid Shoumariyeh Benedikt Csernalabics Elahe Salimi Alizei Matthias Reinscheid Sebastian Giese Kevin Ciminski Georg Kochs Martin Schwemmle Julia Lang-Meli Michelle Maas Natascha Roehlen Vivien Karl Anne Graeser Oezlem Sogukpinar Ivana von Metzler Denise Grathwohl Leo Rasche Holger Hebart Miriam Kull Florian Emmerich Cornelius Florian Waller Justus Duyster Monika Engelhardt Tanja Nicole Hartmann Bertram Bengsch Tobias Boettler Christoph Neumann-Haefelin Maike Hofmann Robert Thimme Hendrik Luxenburger |
| author_sort | Khalid Shoumariyeh |
| collection | DOAJ |
| description | Background: Multiple myeloma (MM) patients are at high risk of severe infections including COVID-19 due to an immune dysregulation affecting both innate and adaptive immune responses. However, our understanding of the immune responses to infection and vaccination in MM patients is limited. To gain more detailed insights into infection- and vaccine-elicited T cell immunity in MM, we studied the CD8+ T cell response on the single-epitope level in SARS-CoV-2 convalescent and mRNA-vaccinated MM patients. Methods: We compared peptide/MHC class I tetramer-enriched SARS-CoV-2-specific CD8+ T cells and antibody responses in MM patients (convalescent: <i>n</i> = 16, fully vaccinated: <i>n</i> = 5, vaccinated convalescent: <i>n</i> = 5) and healthy controls (HCs) (convalescent: <i>n</i> = 58, fully vaccinated: <i>n</i> = 7) either after infection with SARS-CoV-2 alone, complete mRNA vaccination or SARS-CoV-2 infection and single-shot mRNA vaccination (hybrid immunity). Results: MM patients have lower frequencies and a lower proportion of fully functional virus-specific CD8+ T cells compared to HCs, after both SARS-CoV-2 infection and vaccination. CD8+ T cell memory subset distribution in MM patients is skewed towards reduced frequencies of central memory (T<sub>CM</sub>) T cells and higher frequencies of effector memory 1 (T<sub>EM1</sub>) T cells. In contrast, the humoral immune response was comparable in both cohorts after viral clearance. Notably, CD8+ T cell frequencies as well as the humoral immune response were improved by a single dose of mRNA vaccine in convalescent MM patients. Conclusions: MM patients have relative immunological deficiencies in SARS-CoV-2 immunity but benefit from hybrid immunity. These findings underline the relevance of vaccinations in this vulnerable patient group. |
| format | Article |
| id | doaj-art-139b7f29dd3841dcaa4f950d263f58df |
| institution | OA Journals |
| issn | 2076-393X |
| language | English |
| publishDate | 2024-11-01 |
| publisher | MDPI AG |
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| series | Vaccines |
| spelling | doaj-art-139b7f29dd3841dcaa4f950d263f58df2025-08-20T02:27:41ZengMDPI AGVaccines2076-393X2024-11-011211124910.3390/vaccines12111249Impaired SARS-CoV-2-Specific CD8+ T Cells After Infection or Vaccination but Robust Hybrid T Cell Immunity in Patients with Multiple MyelomaKhalid Shoumariyeh0Benedikt Csernalabics1Elahe Salimi Alizei2Matthias Reinscheid3Sebastian Giese4Kevin Ciminski5Georg Kochs6Martin Schwemmle7Julia Lang-Meli8Michelle Maas9Natascha Roehlen10Vivien Karl11Anne Graeser12Oezlem Sogukpinar13Ivana von Metzler14Denise Grathwohl15Leo Rasche16Holger Hebart17Miriam Kull18Florian Emmerich19Cornelius Florian Waller20Justus Duyster21Monika Engelhardt22Tanja Nicole Hartmann23Bertram Bengsch24Tobias Boettler25Christoph Neumann-Haefelin26Maike Hofmann27Robert Thimme28Hendrik Luxenburger29Department of Medicine I, Medical Center—University of Freiburg, Faculty of Medicine, University of Freiburg, 79098 Freiburg, GermanyDepartment of Medicine II (Gastroenterology, Hepatology, Endocrinology and Infectious Diseases), Freiburg University Medical Center, Faculty of Medicine, University of Freiburg, 79098 Freiburg, GermanyDepartment of Medicine II (Gastroenterology, Hepatology, Endocrinology and Infectious Diseases), Freiburg University Medical Center, Faculty of Medicine, University of Freiburg, 79098 Freiburg, GermanyDepartment of Medicine II (Gastroenterology, Hepatology, Endocrinology and Infectious Diseases), Freiburg University Medical Center, Faculty of Medicine, University of Freiburg, 79098 Freiburg, GermanyInstitute of Virology, Freiburg University Medical Center, Faculty of Medicine, University of Freiburg, 79098 Freiburg, GermanyInstitute of Virology, Freiburg University Medical Center, Faculty of Medicine, University of Freiburg, 79098 Freiburg, GermanyInstitute of Virology, Freiburg University Medical Center, Faculty of Medicine, University of Freiburg, 79098 Freiburg, GermanyInstitute of Virology, Freiburg University Medical Center, Faculty of Medicine, University of Freiburg, 79098 Freiburg, GermanyDepartment of Medicine II (Gastroenterology, Hepatology, Endocrinology and Infectious Diseases), Freiburg University Medical Center, Faculty of Medicine, University of Freiburg, 79098 Freiburg, GermanyDepartment of Medicine II (Gastroenterology, Hepatology, Endocrinology and Infectious Diseases), Freiburg University Medical Center, Faculty of Medicine, University of Freiburg, 79098 Freiburg, GermanyDepartment of Medicine II (Gastroenterology, Hepatology, Endocrinology and Infectious Diseases), Freiburg University Medical Center, Faculty of Medicine, University of Freiburg, 79098 Freiburg, GermanyDepartment of Medicine II (Gastroenterology, Hepatology, Endocrinology and Infectious Diseases), Freiburg University Medical Center, Faculty of Medicine, University of Freiburg, 79098 Freiburg, GermanyDepartment of Medicine II (Gastroenterology, Hepatology, Endocrinology and Infectious Diseases), Freiburg University Medical Center, Faculty of Medicine, University of Freiburg, 79098 Freiburg, GermanyDepartment of Medicine II (Gastroenterology, Hepatology, Endocrinology and Infectious Diseases), Freiburg University Medical Center, Faculty of Medicine, University of Freiburg, 79098 Freiburg, GermanyDepartment of Medicine II—Hematology and Oncology, Goethe-University Frankfurt, University Hospital, 60629 Frankfurt am Main, GermanyDepartment of Internal Medicine II, University of Würzburg, 97070 Würzburg, GermanyDepartment of Internal Medicine II, University of Würzburg, 97070 Würzburg, GermanyClinics Ostalb, Stauferklinikum, 73557 Mutlangen, GermanyDepartment of Internal Medicine III, Ulm University Hospital, 89081 Ulm, GermanyInstitute for Transfusion Medicine and Gene Therapy, Freiburg University Medical Center, Faculty of Medicine, University of Freiburg, 79098 Freiburg, GermanyDepartment of Medicine I, Medical Center—University of Freiburg, Faculty of Medicine, University of Freiburg, 79098 Freiburg, GermanyDepartment of Medicine I, Medical Center—University of Freiburg, Faculty of Medicine, University of Freiburg, 79098 Freiburg, GermanyDepartment of Medicine I, Medical Center—University of Freiburg, Faculty of Medicine, University of Freiburg, 79098 Freiburg, GermanyDepartment of Medicine I, Medical Center—University of Freiburg, Faculty of Medicine, University of Freiburg, 79098 Freiburg, GermanyGerman Cancer Consortium (DKTK), Partner Site Freiburg, a Partnership Between DKFZ and University Medical Center Freiburg, 79098 Freiburg, GermanyDepartment of Medicine II (Gastroenterology, Hepatology, Endocrinology and Infectious Diseases), Freiburg University Medical Center, Faculty of Medicine, University of Freiburg, 79098 Freiburg, GermanyDepartment of Medicine II (Gastroenterology, Hepatology, Endocrinology and Infectious Diseases), Freiburg University Medical Center, Faculty of Medicine, University of Freiburg, 79098 Freiburg, GermanyDepartment of Medicine II (Gastroenterology, Hepatology, Endocrinology and Infectious Diseases), Freiburg University Medical Center, Faculty of Medicine, University of Freiburg, 79098 Freiburg, GermanyDepartment of Medicine II (Gastroenterology, Hepatology, Endocrinology and Infectious Diseases), Freiburg University Medical Center, Faculty of Medicine, University of Freiburg, 79098 Freiburg, GermanyDepartment of Medicine II (Gastroenterology, Hepatology, Endocrinology and Infectious Diseases), Freiburg University Medical Center, Faculty of Medicine, University of Freiburg, 79098 Freiburg, GermanyBackground: Multiple myeloma (MM) patients are at high risk of severe infections including COVID-19 due to an immune dysregulation affecting both innate and adaptive immune responses. However, our understanding of the immune responses to infection and vaccination in MM patients is limited. To gain more detailed insights into infection- and vaccine-elicited T cell immunity in MM, we studied the CD8+ T cell response on the single-epitope level in SARS-CoV-2 convalescent and mRNA-vaccinated MM patients. Methods: We compared peptide/MHC class I tetramer-enriched SARS-CoV-2-specific CD8+ T cells and antibody responses in MM patients (convalescent: <i>n</i> = 16, fully vaccinated: <i>n</i> = 5, vaccinated convalescent: <i>n</i> = 5) and healthy controls (HCs) (convalescent: <i>n</i> = 58, fully vaccinated: <i>n</i> = 7) either after infection with SARS-CoV-2 alone, complete mRNA vaccination or SARS-CoV-2 infection and single-shot mRNA vaccination (hybrid immunity). Results: MM patients have lower frequencies and a lower proportion of fully functional virus-specific CD8+ T cells compared to HCs, after both SARS-CoV-2 infection and vaccination. CD8+ T cell memory subset distribution in MM patients is skewed towards reduced frequencies of central memory (T<sub>CM</sub>) T cells and higher frequencies of effector memory 1 (T<sub>EM1</sub>) T cells. In contrast, the humoral immune response was comparable in both cohorts after viral clearance. Notably, CD8+ T cell frequencies as well as the humoral immune response were improved by a single dose of mRNA vaccine in convalescent MM patients. Conclusions: MM patients have relative immunological deficiencies in SARS-CoV-2 immunity but benefit from hybrid immunity. These findings underline the relevance of vaccinations in this vulnerable patient group.https://www.mdpi.com/2076-393X/12/11/1249multiple myelomaimmunosuppressionCOVID-19SARS-CoV-2mRNA vaccinationinfection |
| spellingShingle | Khalid Shoumariyeh Benedikt Csernalabics Elahe Salimi Alizei Matthias Reinscheid Sebastian Giese Kevin Ciminski Georg Kochs Martin Schwemmle Julia Lang-Meli Michelle Maas Natascha Roehlen Vivien Karl Anne Graeser Oezlem Sogukpinar Ivana von Metzler Denise Grathwohl Leo Rasche Holger Hebart Miriam Kull Florian Emmerich Cornelius Florian Waller Justus Duyster Monika Engelhardt Tanja Nicole Hartmann Bertram Bengsch Tobias Boettler Christoph Neumann-Haefelin Maike Hofmann Robert Thimme Hendrik Luxenburger Impaired SARS-CoV-2-Specific CD8+ T Cells After Infection or Vaccination but Robust Hybrid T Cell Immunity in Patients with Multiple Myeloma Vaccines multiple myeloma immunosuppression COVID-19 SARS-CoV-2 mRNA vaccination infection |
| title | Impaired SARS-CoV-2-Specific CD8+ T Cells After Infection or Vaccination but Robust Hybrid T Cell Immunity in Patients with Multiple Myeloma |
| title_full | Impaired SARS-CoV-2-Specific CD8+ T Cells After Infection or Vaccination but Robust Hybrid T Cell Immunity in Patients with Multiple Myeloma |
| title_fullStr | Impaired SARS-CoV-2-Specific CD8+ T Cells After Infection or Vaccination but Robust Hybrid T Cell Immunity in Patients with Multiple Myeloma |
| title_full_unstemmed | Impaired SARS-CoV-2-Specific CD8+ T Cells After Infection or Vaccination but Robust Hybrid T Cell Immunity in Patients with Multiple Myeloma |
| title_short | Impaired SARS-CoV-2-Specific CD8+ T Cells After Infection or Vaccination but Robust Hybrid T Cell Immunity in Patients with Multiple Myeloma |
| title_sort | impaired sars cov 2 specific cd8 t cells after infection or vaccination but robust hybrid t cell immunity in patients with multiple myeloma |
| topic | multiple myeloma immunosuppression COVID-19 SARS-CoV-2 mRNA vaccination infection |
| url | https://www.mdpi.com/2076-393X/12/11/1249 |
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