mRNA-1273 vaccinated inflammatory bowel disease patients receiving TNF inhibitors develop broad and robust SARS-CoV-2-specific CD8+ T cell responses
Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved..
SARS-CoV-2-specific CD8+ T cells recognize conserved viral peptides and in the absence of cross-reactive antibodies form an important line of protection against emerging viral variants as they ameliorate disease severity. SARS-CoV-2 mRNA vaccines induce robust spike-specific antibody and T cell responses in healthy individuals, but their effectiveness in patients with chronic immune-mediated inflammatory disorders (IMIDs) is less well defined. These patients are often treated with systemic immunosuppressants, which may negatively affect vaccine-induced immunity. Indeed, TNF inhibitor (TNFi)-treated inflammatory bowel disease (IBD) patients display reduced ability to maintain SARS-CoV-2 antibody responses post-vaccination, yet the effects on CD8+ T cells remain unclear. Here, we analyzed the impact of IBD and TNFi treatment on mRNA-1273 vaccine-induced CD8+ T cell responses compared to healthy controls in SARS-CoV-2 experienced and inexperienced patients. CD8+ T cells were analyzed for their ability to recognize 32 SARS-CoV-2-specific epitopes, restricted by 10 common HLA class I allotypes using heterotetramer combinatorial coding. This strategy allowed in-depth ex vivo profiling of the vaccine-induced CD8+ T cell responses using phenotypic and activation markers. mRNA vaccination of TNFi-treated and untreated IBD patients induced robust spike-specific CD8+ T cell responses with a predominant central memory and activated phenotype, comparable to those in healthy controls. Prominent non-spike-specific CD8+ T cell responses were observed in SARS-CoV-2 experienced donors prior to vaccination. Non-spike-specific CD8+ T cells persisted and spike-specific CD8+ T cells notably expanded after vaccination in these patient cohorts. Our data demonstrate that regardless of TNFi treatment or prior SARS-CoV-2 infection, IBD patients benefit from vaccination by inducing a robust spike-specific CD8+ T cell response.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:144 |
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| Enthalten in: |
Journal of autoimmunity - 144(2024) vom: 17. Apr., Seite 103175 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
van den Dijssel, Jet [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 17.04.2024 Date Revised 17.04.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.jaut.2024.103175 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a SARS-CoV-2-specific CD8+ T cells recognize conserved viral peptides and in the absence of cross-reactive antibodies form an important line of protection against emerging viral variants as they ameliorate disease severity. SARS-CoV-2 mRNA vaccines induce robust spike-specific antibody and T cell responses in healthy individuals, but their effectiveness in patients with chronic immune-mediated inflammatory disorders (IMIDs) is less well defined. These patients are often treated with systemic immunosuppressants, which may negatively affect vaccine-induced immunity. Indeed, TNF inhibitor (TNFi)-treated inflammatory bowel disease (IBD) patients display reduced ability to maintain SARS-CoV-2 antibody responses post-vaccination, yet the effects on CD8+ T cells remain unclear. Here, we analyzed the impact of IBD and TNFi treatment on mRNA-1273 vaccine-induced CD8+ T cell responses compared to healthy controls in SARS-CoV-2 experienced and inexperienced patients. CD8+ T cells were analyzed for their ability to recognize 32 SARS-CoV-2-specific epitopes, restricted by 10 common HLA class I allotypes using heterotetramer combinatorial coding. This strategy allowed in-depth ex vivo profiling of the vaccine-induced CD8+ T cell responses using phenotypic and activation markers. mRNA vaccination of TNFi-treated and untreated IBD patients induced robust spike-specific CD8+ T cell responses with a predominant central memory and activated phenotype, comparable to those in healthy controls. Prominent non-spike-specific CD8+ T cell responses were observed in SARS-CoV-2 experienced donors prior to vaccination. Non-spike-specific CD8+ T cells persisted and spike-specific CD8+ T cells notably expanded after vaccination in these patient cohorts. Our data demonstrate that regardless of TNFi treatment or prior SARS-CoV-2 infection, IBD patients benefit from vaccination by inducing a robust spike-specific CD8+ T cell response | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Adalimumab | |
| 650 | 4 | |a CD8(+) T cells | |
| 650 | 4 | |a Inflammatory bowel disease | |
| 650 | 4 | |a Infliximab | |
| 650 | 4 | |a SARS-CoV-2 vaccination | |
| 650 | 4 | |a TNF inhibitor | |
| 650 | 7 | |a 2019-nCoV Vaccine mRNA-1273 |2 NLM | |
| 650 | 7 | |a EPK39PL4R4 |2 NLM | |
| 650 | 7 | |a Tumor Necrosis Factor Inhibitors |2 NLM | |
| 650 | 7 | |a Antibodies |2 NLM | |
| 650 | 7 | |a Antibodies, Viral |2 NLM | |
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| 700 | 1 | |a Konijn, Veronique Al |e verfasserin |4 aut | |
| 700 | 1 | |a Kummer, Laura Yl |e verfasserin |4 aut | |
| 700 | 1 | |a Hagen, Ruth R |e verfasserin |4 aut | |
| 700 | 1 | |a Kuijper, Lisan H |e verfasserin |4 aut | |
| 700 | 1 | |a Wieske, Luuk |e verfasserin |4 aut | |
| 700 | 1 | |a van Dam, Koos Pj |e verfasserin |4 aut | |
| 700 | 1 | |a Stalman, Eileen W |e verfasserin |4 aut | |
| 700 | 1 | |a Steenhuis, Maurice |e verfasserin |4 aut | |
| 700 | 1 | |a Geerdes, Dionne M |e verfasserin |4 aut | |
| 700 | 1 | |a Mok, Juk Yee |e verfasserin |4 aut | |
| 700 | 1 | |a Kragten, Angela Hm |e verfasserin |4 aut | |
| 700 | 1 | |a Menage, Charlotte |e verfasserin |4 aut | |
| 700 | 1 | |a Koets, Lianne |e verfasserin |4 aut | |
| 700 | 1 | |a Veldhuisen, Barbera |e verfasserin |4 aut | |
| 700 | 1 | |a Verstegen, Niels Jm |e verfasserin |4 aut | |
| 700 | 1 | |a van der Schoot, C Ellen |e verfasserin |4 aut | |
| 700 | 1 | |a van Esch, Wim Je |e verfasserin |4 aut | |
| 700 | 1 | |a D'Haens, Geert Ram |e verfasserin |4 aut | |
| 700 | 1 | |a Löwenberg, Mark |e verfasserin |4 aut | |
| 700 | 1 | |a Volkers, Adriaan G |e verfasserin |4 aut | |
| 700 | 1 | |a Rispens, Theo |e verfasserin |4 aut | |
| 700 | 1 | |a Kuijpers, Taco W |e verfasserin |4 aut | |
| 700 | 1 | |a Eftimov, Filip |e verfasserin |4 aut | |
| 700 | 1 | |a van Gisbergen, Klaas Pjm |e verfasserin |4 aut | |
| 700 | 1 | |a van Ham, S Marieke |e verfasserin |4 aut | |
| 700 | 1 | |a Ten Brinke, Anja |e verfasserin |4 aut | |
| 700 | 1 | |a van de Sandt, Carolien E |e verfasserin |4 aut | |
| 700 | 0 | |a T2B! immunity against SARS-CoV-2 study group |e verfasserin |4 aut | |
| 700 | 1 | |a van Allaart, Renée Cf |e investigator |4 oth | |
| 700 | 1 | |a Baars, Adája E |e investigator |4 oth | |
| 700 | 1 | |a Bekkenk, Marcel W |e investigator |4 oth | |
| 700 | 1 | |a Bemelman, Frederike J |e investigator |4 oth | |
| 700 | 1 | |a Boekel, Laura |e investigator |4 oth | |
| 700 | 1 | |a Bos, Amélie V |e investigator |4 oth | |
| 700 | 1 | |a Bosma, Angela L |e investigator |4 oth | |
| 700 | 1 | |a Broens, Bo |e investigator |4 oth | |
| 700 | 1 | |a Brusse, Esther |e investigator |4 oth | |
| 700 | 1 | |a Busch, Matthias H |e investigator |4 oth | |
| 700 | 1 | |a Cristianawati, Olvi |e investigator |4 oth | |
| 700 | 1 | |a van Doorn, Pieter A |e investigator |4 oth | |
| 700 | 1 | |a Elias, George |e investigator |4 oth | |
| 700 | 1 | |a van Els, Cécile Acm |e investigator |4 oth | |
| 700 | 1 | |a van Gils, Marit J |e investigator |4 oth | |
| 700 | 1 | |a Goedee, H Stephan |e investigator |4 oth | |
| 700 | 1 | |a Hijnen, Dirk Jan |e investigator |4 oth | |
| 700 | 1 | |a Hilhorst, Marc L |e investigator |4 oth | |
| 700 | 1 | |a Horváth, Barbara |e investigator |4 oth | |
| 700 | 1 | |a Jallah, Papay Bp |e investigator |4 oth | |
| 700 | 1 | |a de Jongh, Rivka |e investigator |4 oth | |
| 700 | 1 | |a Mirfazeli, Elham S |e investigator |4 oth | |
| 700 | 1 | |a Musters, Annelie H |e investigator |4 oth | |
| 700 | 1 | |a Keijser, Jim Bd |e investigator |4 oth | |
| 700 | 1 | |a van Kempen, Zoé LE |e investigator |4 oth | |
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| 700 | 1 | |a Kreher, Christine |e investigator |4 oth | |
| 700 | 1 | |a de Leeuw, Karina |e investigator |4 oth | |
| 700 | 1 | |a van der Kooi, Anneke J |e investigator |4 oth | |
| 700 | 1 | |a van Ouwerkerk, Lotte |e investigator |4 oth | |
| 700 | 1 | |a van Paassen, Pieter |e investigator |4 oth | |
| 700 | 1 | |a Cabeza, Virginia Palomares |e investigator |4 oth | |
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