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.