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Publication

mRNA-1273 vaccinated inflammatory bowel disease patients receiving TNF inhibitors develop broad and robust SARS-CoV-2-specific CD8+ T cell responses


Authors:

  • van den Dijssel, Jet
  • Duurland, Mariël C.
  • Konijn, Veronique AL.
  • Kummer, Laura YL.
  • Hagen, Ruth R.
  • Kuijper, Lisan H.
  • Wieske, Luuk
  • van Dam, Koos PJ.
  • Stalman, Eileen W.
  • Steenhuis, Maurice
  • Geerdes, Dionne M.
  • Mok, Juk Yee
  • Kragten, Angela HM.
  • Menage, Charlotte
  • Koets, Lianne
  • Veldhuisen, Barbera
  • Verstegen, Niels JM.
  • van der Schoot, C Ellen
  • van Esch, Wim JE.
  • D'Haens, Geert RAM.
  • Löwenberg, Mark
  • Volkers, Adriaan G.
  • Rispens, Theo
  • Kuijpers, Taco W.
  • Eftimov, Filip
  • van Gisbergen, Klaas PJM.
  • van Ham, S Marieke
  • ten Brinke, Anja
  • van de Sandt, Carolien E.
  • van Allaart, Renée CF.
  • Baars, Adája E.
  • Bekkenk, Marcel W.
  • Bemelman, Frederike J.
  • Boekel, Laura
  • Bos, Amélie V.
  • Bosma, Angela L.
  • Broens, Bo
  • Brusse, Esther
  • Busch, Matthias H.
  • Cristianawati, Olvi
  • van Doorn, Pieter A.
  • Elias, George
  • van Els, Cécile ACM.
  • van Gils, Marit J.
  • Goedee, H Stephan
  • Hijnen, Dirk Jan
  • Hilhorst, Marc L.
  • Horváth, Barbara
  • Jallah, Papay BP.
  • de Jongh, Rivka
  • Mirfazeli, Elham S.
  • Musters, Annelie H.
  • Keijser, Jim BD.
  • van Kempen, Zoé LE.
  • Killestein, Joep
  • Kreher, Christine
  • de Leeuw, Karina
  • van der Kooi, Anneke J.
  • van Ouwerkerk, Lotte
  • van Paassen, Pieter
  • Cabeza, Virginia Palomares
  • Parra Sanchez, Agner R.
  • Ludo van der Pol, W.
  • Post, Nicoline F.
  • Raaphorst, Joop
  • Ruiter, Annabel M.
  • Rutgers, Abraham
  • Schreurs, Corine RG.
  • Spuls, Phyllis I.
  • Takkenberg, R Bart
  • Tas, Sander W.
  • Teng, YK Onno
  • Vegting, Yosta
  • Verschuuren, Jan JGM.
  • Voskuyl, Alexandre E.
  • de Wit, Jelle
  • Wolbink, Gerrit J.
  • van der Woude, Diane
  • Zwinderman, Koos AH.

Details:

Journal of Autoimmunity, Volume 144, 2024-04-30

Article Link: Click here

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.